183 results on '"Rhombencephalon abnormalities"'
Search Results
2. Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.
- Author
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Krajden Haratz K, Oliveira Szejnfeld P, Govindaswamy M, Leibovitz Z, Gindes L, Severino M, Rossi A, Paladini D, Garcia Rodriguez R, Ben-Sira L, Borkowski Tillman T, Gupta R, Lotem G, Raz N, Hamamoto TENK, Kidron D, Arad A, Birnbaum R, Brussilov M, Pomar L, Vial Y, Leventer RJ, McGillivray G, Fink M, Krzeszowski W, Fernandes Moron A, Lev D, Tamarkin M, Shalev J, Har Toov J, Lerman-Sagie T, and Malinger G
- Subjects
- Abnormalities, Multiple embryology, Adult, Cerebellar Vermis diagnostic imaging, Cerebellar Vermis embryology, Cerebellum diagnostic imaging, Cerebellum embryology, Eye Abnormalities embryology, Female, Gestational Age, Humans, Kidney Diseases, Cystic embryology, Magnetic Resonance Imaging, Multimodal Imaging, Nervous System Malformations embryology, Pregnancy, Retina diagnostic imaging, Retina embryology, Retrospective Studies, Rhombencephalon diagnostic imaging, Rhombencephalon embryology, Severity of Illness Index, Ultrasonography, Prenatal, Abnormalities, Multiple diagnostic imaging, Cerebellar Vermis abnormalities, Cerebellum abnormalities, Eye Abnormalities diagnostic imaging, Kidney Diseases, Cystic diagnostic imaging, Nervous System Malformations diagnostic imaging, Neuroimaging, Prenatal Diagnosis methods, Retina abnormalities, Rhombencephalon abnormalities
- Abstract
Objectives: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly., Methods: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES., Results: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3
rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption., Conclusions: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)- Published
- 2021
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3. Is ventriculomegaly and hindbrain herniation seen before and after prenatal neural tube defect repair associated with a worse functional level than anatomical level at birth?
- Author
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Corroenne R, Zarutskie A, Guimaraes C, Yepez M, Torres P, Shetty A, Lee W, Espinoza J, Shamshirsaz AA, Nassr AA, Belfort M, Whitehead W, and Sanz Cortes M
- Subjects
- Adult, Cohort Studies, Female, Humans, Hydrocephalus epidemiology, Hydrocephalus surgery, Infant, Newborn, Magnetic Resonance Imaging methods, Neural Tube Defects complications, Neural Tube Defects epidemiology, Neurosurgical Procedures adverse effects, Neurosurgical Procedures methods, Neurosurgical Procedures statistics & numerical data, Pregnancy, Prenatal Care methods, Retrospective Studies, Rhombencephalon injuries, Rhombencephalon surgery, Texas epidemiology, Functional Status, Hydrocephalus complications, Neural Tube Defects surgery, Rhombencephalon abnormalities
- Abstract
Objective: To determine if the evaluation of the fetal ventricular system and hindbrain herniation (HBH) is associated with motor outcome at birth in prenatally repaired open neural tube defect (NTD)., Methods: Retrospective cohort study of 47 patients with NTD who underwent prenatal repair (17 fetoscopic; 30 open-hysterotomy). At referral and 6 weeks postoperatively, the degree of HBH, ventricular atrial widths and ventricular volume were evaluated by MRI. Head circumference and ventricular atrial widths were measured on ultrasound at referral and during the last ultrasound before delivery. Anatomic level of the lesion (LL) was determined based on the upper bony spinal defect detected by ultrasound. We considered the functional level as worse than anatomical level at birth when the motor level was equal or worse than the anatomical LL., Results: 26% (12/47) of the cases showed worse functional level than anatomical level at birth. Having a HBH below C1 at the time of referral was associated with a worse functional level than anatomical level at birth (OR = 9.7, CI95 [2.2-42.8], p < 0.01). None of the other brain parameters showed a significant association with motor outcomes at birth., Conclusions: HBH below C1 before surgery was associated with a worse functional level than anatomical level at birth., (© 2021 John Wiley & Sons Ltd.)
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- 2021
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4. Early diagnosis of rhombencephalosynapsis: the limits of intracranial translucency at first-trimester screening and a plea for assessment of aqueduct of Sylvius.
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Macé P, Ville Y, Bessière B, and Quarello E
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- Abortion, Eugenic, Cerebral Aqueduct diagnostic imaging, Cerebral Aqueduct embryology, Cerebral Ventricles diagnostic imaging, Cerebral Ventricles embryology, Early Diagnosis, Female, Humans, Hydrocephalus diagnosis, Hydrocephalus embryology, Medical Illustration, Nervous System Malformations embryology, Pregnancy, Pregnancy Trimester, First, Rhombencephalon diagnostic imaging, Rhombencephalon embryology, Cerebral Aqueduct abnormalities, Cerebral Ventricles abnormalities, Nervous System Malformations diagnosis, Prenatal Diagnosis methods, Rhombencephalon abnormalities
- Published
- 2021
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5. Zebrafish disease model of human RNASET2-deficient cystic leukoencephalopathy displays abnormalities in early microglia.
- Author
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Weber T, Schlotawa L, Dosch R, Hamilton N, Kaiser J, Schiller S, Wenske B, Gärtner J, and Henneke M
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- Animals, Apoptosis, Disease Susceptibility, Humans, Larva, Neurons metabolism, Organogenesis genetics, Rhombencephalon abnormalities, Rhombencephalon embryology, Rhombencephalon metabolism, Zebrafish, Genetic Association Studies methods, Genetic Predisposition to Disease, Leukoencephalopathies diagnosis, Leukoencephalopathies genetics, Leukoencephalopathies metabolism, Microglia metabolism, Phenotype, Ribonucleases deficiency, Tumor Suppressor Proteins deficiency
- Abstract
Human infantile-onset RNASET2-deficient cystic leukoencephalopathy is a Mendelian mimic of in utero cytomegalovirus brain infection with prenatally developing inflammatory brain lesions. We used an RNASET2-deficient zebrafish model to elucidate the underlying disease mechanisms. Mutant and wild-type zebrafish larvae brain development between 2 and 5 days post fertilization (dpf) was examined by confocal live imaging in fluorescent reporter lines of the major types of brain cells. In contrast to wild-type brains, RNASET2-deficient larvae displayed increased numbers of microglia with altered morphology, often containing inclusions of neurons. Furthermore, lysosomes within distinct populations of the myeloid cell lineage including microglia showed increased lysosomal staining. Neurons and oligodendrocyte precursor cells remained unaffected. This study provides a first look into the prenatal onset pathomechanisms of human RNASET2-deficient leukoencephalopathy, linking this inborn lysosomal disease to the innate immune system and other immune-related childhood encephalopathies like Aicardi-Goutières syndrome (AGS)., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)
- Published
- 2020
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6. Genetic evaluation including exome sequencing of two patients with Gomez-Lopez-Hernandez syndrome: Case reports and review of the literature.
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Lindsay F, Anderson I, Wentzensen IM, Suhrbier D, and Stevens CA
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- Abnormalities, Multiple genetics, Adolescent, Alopecia genetics, Cerebellum pathology, Craniofacial Abnormalities genetics, Female, Growth Disorders genetics, Humans, Male, Neurocutaneous Syndromes genetics, Phenotype, Rhombencephalon abnormalities, Exome Sequencing, Abnormalities, Multiple pathology, Alopecia pathology, Cerebellum abnormalities, Craniofacial Abnormalities pathology, Exome genetics, Growth Disorders pathology, Neurocutaneous Syndromes pathology, Rhombencephalon pathology
- Abstract
Rhombencephalosynapsis (RES) is a rare congenital anomaly of the hindbrain characterized by fusion of the cerebellar hemispheres, cerebellar peduncles, and dentate nuclei with vermian absence or hypogenesis. This anomaly can be isolated or part of a larger spectrum of cerebral abnormalities. At least 90 cases are described in the literature and it has been associated with VACTERL and Gomez-Lopez-Hernandez syndrome (GLHS). The most common congenital syndrome associated with RES is GLHS, a rare presumed genetic disorder with over 30 cases thus far described in the literature. No genetic cause has been identified for RES or GLHS. We report two probands diagnosed with GLHS based on clinical criteria. Each proband had RES and bi-parietal scalp alopecia as well as neurologic findings and phenotypic features including trigeminal anesthesia, borderline hypertelorism, midface retrusion, and motor delay. Oliginucleotide-SNP microarray on the male proband revealed a 1.05 Mb copy duplication of uncertain clinical significance at 15q21.3 while oligonucleotide-SNP microarray for the female proband did not reveal any abnormalities. Exome sequencing (ES) was performed on both patients and did not identify any variants that could explain the GLHS phenotype. To our knowledge, these are the first two patients with GLHS described in the literature to undergo ES. Both patients had mild neurologic manifestations requiring physical therapy in early life without known diagnostic cause. Patients found to have scalp alopecia or trigeminal anesthesia with gross motor delay should be evaluated for RES or GLHS as well as screened for associated syndromes and have a complete neurodevelopmental evaluation., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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7. In Utero Restoration of Hindbrain Herniation in Fetal Myelomeningocele as Part of Prenatal Regenerative Therapy Program at Mayo Clinic.
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Ruano R, Daniels DJ, Ahn ES, Ibirogba ER, Lu VM, Snyder KA, Trinidad MC, Carey WA, Colby CE, Kolbe AB, Arendt KW, Segura L, Sviggum HP, Qureshi MY, Famuyide A, and Terzic A
- Subjects
- Adult, Encephalocele surgery, Female, Fetus abnormalities, Fetus surgery, Humans, Meningomyelocele surgery, Pregnancy, Prenatal Care methods, Regenerative Medicine classification, Rhombencephalon abnormalities, Rhombencephalon surgery, Encephalocele embryology, Meningomyelocele embryology, Regenerative Medicine methods, Rhombencephalon embryology
- Abstract
Objective: To assess our initial experience with prenatal restoration of hindbrain herniation following in utero repair of myelomeningocele (MMC)., Patients and Methods: Three consecutive patients with prenatally diagnosed MMC (between January 1, 2018 and September 30, 2018) were managed with open in utero surgery. As per institutional review board approval and following a protocol designed at the Mayo Clinic Maternal & Fetal Center, fetal intervention was offered between 19 0/7 and 25 6/7 weeks of gestation. Prenatal improvement of hindbrain herniation was the declared restorative end point. Obstetrical and perinatal outcomes were also assessed., Results: Diagnosis of MMC was confirmed upon referral between 20 and 21 weeks' gestation by using fetal ultrasound and magnetic resonance imaging. In all cases reported here, the spinal defect was lumbosacral with evidence of hindbrain herniation. Open in utero MMC repair was performed between 24 and 25 weeks' gestation with no notable perioperative complications. Postprocedure fetal magnetic resonance imaging performed 6 weeks after in utero repair documented improvement of hindbrain herniation. Deliveries were at 37 weeks by cesarean section without complications. Most recent postnatal follow-ups were unremarkable at both 11 months (baby 1) and 3 months of age (baby 2), with mild ventriculomegaly. Antenatal and postnatal follow-up of baby 3 at 1 month of age was also unremarkable., Conclusion: Our study highlights the prenatal restoration of hindbrain herniation following in utero MMC repair in all cases presented here as an example of a prenatal regenerative therapy program in our institution., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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8. Neurosurgeons' opinions on the prenatal management of myelomeningocele.
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Gadjradj PS, Spoor JKH, Eggink AJ, Wijnen R, Miller JL, Rosner M, Groves ML, DeKoninck PLJ, Harhangi BS, Baschat A, van Veelen ML, and de Jong THR
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- Female, Fetoscopy methods, Fetus surgery, Humans, Pregnancy, Meningomyelocele surgery, Neurosurgeons, Neurosurgical Procedures methods, Rhombencephalon abnormalities
- Abstract
Objective: Improvements in imaging and surgical technological innovations have led to the increasing implementation of fetal surgical techniques. Open fetal surgery has demonstrated more favorable clinical outcomes in children born with open myelomeningocele (MMC) than those following postnatal repair. However, primarily because of maternal risks but also because of fetal risks, fetal surgery for MMC remains controversial. Here, the authors evaluated the contemporary management of MMC in the hope of identifying barriers and facilitators for neurosurgeons in providing fetal surgery for MMC., Methods: An online survey was emailed to members of the Congress of Neurological Surgeons (CNS) and the International Society for Pediatric Neurosurgery (ISPN) in March 2019. The survey focused on 1) characteristics of the respondents, 2) the practice of counseling on and managing prenatally diagnosed MMC, and 3) barriers, facilitators, and expectations of fetal surgery for MMC. Reminders were sent to improve the response rate., Results: A total of 446 respondents filled out the survey, most (59.2%) of whom specialized in pediatric neurosurgery. The respondents repaired an average of 9.6 MMC defects per year, regardless of technique. Regardless of the departments in which respondents were employed, 91.0% provided postnatal repair of MMC, 13.0% open fetal repair, and 4.9% fetoscopic repair. According to the surgeons, the most important objections to performing open fetal surgery were a lack of cases available to become proficient in the technique (33.8%), the risk of maternal complications (23.6%), and concern for fetal complications (15.2%). The most important facilitators according to advocates of prenatal closure are a decreased rate of shunt dependency (37.8%), a decreased rate of hindbrain herniation (27.0%), and an improved rate of motor function (18.9%). Of the respondents, only 16.9% agreed that open fetal surgery should be the standard of care., Conclusions: The survey results showed diversity in the management of patients with MMC. In addition, significant diversity remains regarding fetal surgery for MMC closure. Despite the apparent benefits of open fetal surgery in selected pregnancies, only a minority of centers and providers offer this technique. As a more technically demanding technique that requires multidisciplinary effort with less well-established long-term outcomes, fetoscopic surgery may face similar limited implementation, although the surgery may pose fewer maternal risks than open fetal surgery. Centralization of prenatal treatment to tertiary care referral centers, as well as the use of sophisticated training models, may help to augment the most commonly cited objection to the implementation of prenatal closure, which is the overall limited caseload.
- Published
- 2019
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9. Fourth ventricle index: sonographic marker for severe fetal vermian dysgenesis/agenesis.
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Haratz KK, Shulevitz SL, Leibovitz Z, Lev D, Shalev J, Tomarkin M, Malinger G, Lerman-Sagie T, and Gindes L
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- Abnormalities, Multiple diagnostic imaging, Abnormalities, Multiple pathology, Cerebellar Diseases diagnostic imaging, Cerebellar Diseases epidemiology, Cerebellar Diseases pathology, Cerebellum abnormalities, Cerebellum diagnostic imaging, Cerebellum pathology, Cross-Sectional Studies, Developmental Disabilities diagnostic imaging, Developmental Disabilities epidemiology, Developmental Disabilities pathology, Eye Abnormalities diagnostic imaging, Eye Abnormalities pathology, Female, Fetus, Fourth Ventricle anatomy & histology, Fourth Ventricle pathology, Gestational Age, Humans, Infant, Kidney Diseases, Cystic diagnostic imaging, Kidney Diseases, Cystic pathology, Mesencephalon abnormalities, Nervous System Malformations diagnostic imaging, Nervous System Malformations epidemiology, Nervous System Malformations pathology, Pregnancy, Prospective Studies, Retina abnormalities, Retina diagnostic imaging, Retina pathology, Retrospective Studies, Rhombencephalon abnormalities, Ultrasonography, Prenatal methods, Fourth Ventricle diagnostic imaging, Mesencephalon diagnostic imaging, Prenatal Diagnosis standards, Rhombencephalon diagnostic imaging
- Abstract
Objective: Prenatal diagnosis of midbrain-hindbrain (MB-HB) malformations relies primarily on abnormal size and shape of the cerebellum and retrocerebellar space, particularly 'open fourth ventricle' (4V), the most common indicator of MB-HB malformations. The aim of this study was to present the fourth ventricle index (4VI), and to evaluate its role as a marker for severe vermian dysgenesis/agenesis in cases without open 4V., Methods: This was a prospective cross-sectional study of patients with singleton low-risk pregnancy at 14 + 1 to 36 + 6 gestational weeks presenting between May 2016 and November 2017 for routine ultrasound examination. Axial images of the fetal 4V were obtained and the 4VI was calculated as the ratio between the laterolateral and the anteroposterior diameters. Reference ranges were constructed and retrospectively collected values from 44 fetuses with confirmed anomalies involving severe vermian dysgenesis/agenesis (Joubert syndrome and related disorders, rhombencephalosynapsis, cobblestone malformations and cerebellar hypoplasia) but without open 4V were compared with the normal values., Results: In total, 384 healthy fetuses were enrolled into the study, from which reference ranges were produced, and 44 cases were collected retrospectively. The 4VI in the normal fetuses was always > 1. In affected fetuses, it was always below mean -2 SD and < 1., Conclusions: The 4VI is a sonographic marker for severe fetal vermian dysgenesis/agenesis in the absence of an open 4V. It may be incorporated easily into the routine brain scan; 4VI < 1 indicates a need for dedicated fetal neuroimaging for diagnosis and prenatal counseling. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)
- Published
- 2019
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10. Rhombencephalosynapsis: Fused cerebellum, confused geneticists.
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Aldinger KA, Dempsey JC, Tully HM, Grout ME, Mehaffey MG, Dobyns WB, and Doherty D
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- Growth Disorders genetics, Humans, Rhombencephalon pathology, Cerebellar Diseases diagnosis, Cerebellar Diseases genetics, Cerebellum abnormalities, Growth Disorders diagnosis, Rhombencephalon abnormalities
- Abstract
Rhombencephalosynapsis (RES) is a unique cerebellar malformation characterized by fusion of the cerebellar hemispheres with partial or complete absence of a recognizable cerebellar vermis. Subsets of patients also have other brain malformations such as midbrain fusion with aqueductal stenosis, characteristic craniofacial features (prominent forehead, flat midface, hypertelorism, ear abnormalities), and somatic malformations (heart, kidney, spine, and limb defects). Similar to known genetic brain malformations, the RES cerebellar malformation is highly stereotyped, yet no genetic causes have been identified. Here, we outline our current understanding of the genetic basis for RES, discuss limitations, and outline future approaches to identifying the causes of this fascinating brain malformation., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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11. Brainstem dysgenesis: beyond Moebius syndrome.
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Munell F, Tormos MA, and Roig-Quilis M
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- Abnormalities, Multiple embryology, Abnormalities, Multiple genetics, Abnormalities, Multiple rehabilitation, Brain Stem embryology, Cerebral Cortex abnormalities, Cerebral Cortex embryology, Disease Progression, Early Diagnosis, Eponyms, Humans, Infant, Newborn, Mesencephalon abnormalities, Mesencephalon embryology, Phenotype, Precision Medicine, Prognosis, Rhombencephalon abnormalities, Rhombencephalon embryology, Syndrome, Abnormalities, Multiple classification, Brain Stem abnormalities
- Abstract
Brainstem dysgenesis designates all those patients with congenital dysfunction of cranial nerves and muscle tone due to prenatal lesions or malformations of the brainstem. This generic term has the advantage over the eponyms Moebius 'expanded' or 'unrestricted', Robin, Cogan or Carey-Fineman-Ziter syndromes in that it has a less restrictive view and provides a frame work that enables a systematic approach to diagnosis and research of most developmental disorders involving the brainstem. The review of the literature and our experience shows that infants with a predominant rombencephalic involvement are due to brainstem prenatal disruptive vascular accidents, while cases with midbrain and cerebellar involvement and widespread malformative syndromes have most likely an underlying genetic cause. Due to phenotypic heterogeneity associated with brainstem dysgenesis, it is crucial to evaluate each case individually and to establish a specific therapeutic plan. Intervention programs should start soon after diagnosis and directed to improve functions needed for daily life activities. Even though the prognosis of patients with brainstem dysgenesis due to prenatal destructive lesions depends on the magnitude of the vascular territory involved, in most patients with brainstem dysgenesis, the prognosis is better than the initial clinical manifestations would indicate.
- Published
- 2018
12. A morphometric assessment of type I Chiari malformation above the McRae line: A retrospective case-control study in 302 adult female subjects.
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Houston JR, Eppelheimer MS, Pahlavian SH, Biswas D, Urbizu A, Martin BA, Bapuraj JR, Luciano M, Allen PA, and Loth F
- Subjects
- Adult, Anatomic Landmarks, Case-Control Studies, Cranial Fossa, Posterior abnormalities, Cranial Fossa, Posterior diagnostic imaging, Female, Humans, Retrospective Studies, Rhombencephalon abnormalities, Rhombencephalon diagnostic imaging, Arnold-Chiari Malformation diagnostic imaging, Magnetic Resonance Imaging methods
- Abstract
Purpose: Type I Chiari malformation (CMI) is a radiologically-defined structural dysmorphism of the hindbrain and posterior cranial fossa (PCF). Traditional radiographic identification of CMI relies on the measurement of the cerebellar tonsils in relation to the foramen magnum with or without associated abnormalities of the neuraxis. The primary goal of this retrospective study was to comprehensively assess morphometric parameters above the McRea line in a group of female CMI patients and normal controls., Material and Methods: Twenty-nine morphological measurements were taken on 302 mid-sagittal MR images of adult female CMI patients (n=162) and healthy controls (n=140). All MR images were voluntarily provided by CMI subjects through an online database and control participant images were obtained through the Human Connectome Project and a local hospital system., Results: Analyses were performed on the full dataset of adult female MR images and a restricted dataset of 229 participants that were equated for age, race, and body mass index. Eighteen group differences were identified in the PCF area that we grouped into three clusters; PCF structures heights, clivus angulation, and odontoid process irregularity. Fourteen group differences persisted after equating our CMI and control groups on demographic characteristics., Conclusion: PCF structures reliably differ in adult female CMI patients relative to healthy controls. These differences reflect structural abnormalities in the osseous and soft tissue structures of the clivus, odontoid process, and cerebellum. Clinical and pathophysiological implications are discussed., (Copyright © 2017. Published by Elsevier Masson SAS.)
- Published
- 2018
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13. Prenatal diagnosis of Joubert syndrome by ultrasound and magnetic resonance imaging - report of three cases.
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Yu X, Zhen Z, Li J, Yang W, and Chen X
- Subjects
- Abnormalities, Multiple classification, Abortion, Eugenic, Adult, Cerebellum diagnostic imaging, Eye Abnormalities classification, Female, Gestational Age, Humans, Infant, Newborn, Kidney Diseases, Cystic classification, Magnetic Resonance Imaging, Pregnancy, Retina diagnostic imaging, Rhombencephalon diagnostic imaging, Rhombencephalon pathology, Ultrasonography, Prenatal, Abnormalities, Multiple diagnostic imaging, Cerebellum abnormalities, Eye Abnormalities diagnostic imaging, Kidney Diseases, Cystic diagnostic imaging, Retina abnormalities, Rhombencephalon abnormalities
- Published
- 2017
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14. Mortality in Joubert syndrome.
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Dempsey JC, Phelps IG, Bachmann-Gagescu R, Glass IA, Tully HM, and Doherty D
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- Abnormalities, Multiple genetics, Abnormalities, Multiple physiopathology, Adolescent, Cerebellum physiopathology, Child, Child, Preschool, Eye Abnormalities complications, Eye Abnormalities genetics, Eye Abnormalities physiopathology, Female, Humans, Kidney Diseases, Cystic complications, Kidney Diseases, Cystic genetics, Kidney Diseases, Cystic physiopathology, Male, Renal Insufficiency complications, Renal Insufficiency genetics, Renal Insufficiency pathology, Retina physiopathology, Rhombencephalon abnormalities, Rhombencephalon physiopathology, Abnormalities, Multiple mortality, Cerebellum abnormalities, Eye Abnormalities mortality, Kidney Diseases, Cystic mortality, Renal Insufficiency mortality, Retina abnormalities
- Abstract
Joubert syndrome (JS) is a rare, recessively inherited neurodevelopmental disorder characterized by a distinctive mid-hindbrain malformation. Little is known about mortality in affected individuals. Identifying the timing and causes of death will allow for development of healthcare guidelines for families and providers and, thus, help to prolong and improve the lives of patients with JS. We evaluated information on 40 deceased individuals with JS to characterize age and cause of death. We compared this population with 525 living individuals with JS to estimate associations between risk of death and extra-neurological features. Genetic causes were examined in both groups. Mean age of death in this cohort was 7.2 years, and the most prevalent causes of death were respiratory failure (35%), particularly in individuals younger than 6 years, and kidney failure (37.5%), which was more common in older individuals. We identified possible associations between risk of death and kidney disease, liver fibrosis, polydactyly, occipital encephalocele, and genetic cause. This work highlights factors (genetic cause, extra-neurological organ involvement, and other malformations) likely to be associated with higher risk of mortality in JS, which should prompt increased monitoring for respiratory issues, kidney disease, and liver fibrosis., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
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15. A rare case of rhombencephalosynapsis and prenatal diagnosis.
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Arisoy R, Erdogdu E, Pekin O, Tugrul S, Aydin H, and Yorganci C
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- Abortion, Induced, Adult, Cerebellar Vermis abnormalities, Cerebellar Vermis diagnostic imaging, Cerebellum diagnostic imaging, Cisterna Magna abnormalities, Cisterna Magna diagnostic imaging, Female, Humans, Pregnancy, Pregnancy Trimester, Second, Rhombencephalon abnormalities, Rhombencephalon diagnostic imaging, Cerebellum abnormalities, Hydrocephalus diagnostic imaging, Malformations of Cortical Development diagnostic imaging, Ultrasonography, Prenatal
- Published
- 2016
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16. Successfully treated symptomatic fusiform basilar artery aneurysm in a patient with hindbrain malformation via inverted Y-stenting.
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Purakal AS, Ginat DT, and Lee SK
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- Adult, Basilar Artery pathology, Humans, Intracranial Aneurysm diagnosis, Male, Treatment Outcome, Basilar Artery surgery, Intracranial Aneurysm surgery, Rhombencephalon abnormalities, Rhombencephalon surgery, Stents
- Abstract
A double overlapping reverse Y-stent approach to creating flow diversion using traditional open-cell stent technology was evaluated as a treatment option symptomatic fusiform basilar aneurysms. A 36-year-old man with a complex hindbrain malformation presented with acute ocular dysmotility due to a rapidly enlarging fusiform basilar artery aneurysm. The aneurysm was treated by insertion of two stents into the vertebrobasilar system in an inverted Y-configuration from the basilar tip to the V4 segments of the bilateral vertebral arteries, essentially creating flow diversion without using a dedicated flow diversion device. This resulted in immediate symptomatic improvement. The stents remained patent and the aneurysm was obliterated at 6 months follow-up. Furthermore, the patient remained free of associated symptoms at 10 months follow-up. Thus, the double stenting technique can be used instead of a flow diversion device to effectively create flow diversion, promote aneurysm sac thrombosis, and lead to resolution of symptoms in large fusiform basilar artery aneurysms., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Published
- 2016
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17. Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.
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Abdel Razek AA and Castillo M
- Subjects
- Humans, Neuroimaging, Magnetic Resonance Imaging, Mesencephalon abnormalities, Rhombencephalon abnormalities
- Abstract
We aim to review the magnetic resonance imaging appearance of malformations of midbrain and hindbrain. These can be classified as predominantly cerebellar malformations, combined cerebellar and brain stem malformations, and predominantly brain stem malformations. The diagnostic criteria for the majority of these morphological malformations are based on neuroimaging findings. The predominantly cerebellar malformations include predominantly vermian hypoplasia seen in Dandy-Walker malformation and rhombencephalosynapsis, global cerebellar hypoplasia reported in lissencephaly and microlissencephaly, and unilateral cerebellar hypoplasia seen in PHACES, vanishing cerebellum, and cerebellar cleft. Cerebellar dysplasias are seen in Chudley-McCullough syndrome, associated with LAMA1 mutations and GPR56 mutations; Lhermitte-Duclos disease; and focal cerebellar dysplasias. Cerebellar hyperplasias are seen in megalencephaly-related syndromes and hemimegalencephaly with ipsilateral cerebellomegaly. Cerebellar and brain stem malformations include tubulinopathies, Joubert syndrome, cobblestone malformations, pontocerebellar hypoplasias, and congenital disorders of glycosylation type Ia. Predominantly brain stem malformations include congenital innervation dysgenesis syndrome, pontine tegmental cap dysplasia, diencephalic-mesencephalic junction dysplasia, disconnection syndrome, and pontine clefts.
- Published
- 2016
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18. Rhombencephalosynapsis: a rare congenital anomaly presenting with seizure and developmental delay.
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Shahrzad M and Gold M
- Subjects
- Attention Deficit Disorder with Hyperactivity pathology, Child, Humans, Male, Rhombencephalon pathology, Tomography, X-Ray Computed, Attention Deficit Disorder with Hyperactivity etiology, Developmental Disabilities complications, Developmental Disabilities pathology, Rhombencephalon abnormalities, Seizures complications, Seizures pathology
- Published
- 2015
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19. Congenital basis of posterior fossa anomalies.
- Author
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Cotes C, Bonfante E, Lazor J, Jadhav S, Caldas M, Swischuk L, and Riascos R
- Subjects
- Abnormalities, Multiple, Arachnoid Cysts embryology, Arnold-Chiari Malformation embryology, Cerebellar Diseases embryology, Cerebellum abnormalities, Cranial Fossa, Posterior embryology, Dandy-Walker Syndrome embryology, Eye Abnormalities embryology, Hamartoma Syndrome, Multiple embryology, Humans, Kidney Diseases, Cystic embryology, Mesencephalon embryology, Retina abnormalities, Retina embryology, Rhombencephalon embryology, Walker-Warburg Syndrome embryology, Arachnoid Cysts congenital, Cerebellar Diseases congenital, Cranial Fossa, Posterior abnormalities, Hamartoma Syndrome, Multiple congenital, Mesencephalon abnormalities, Rhombencephalon abnormalities
- Abstract
The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the embryologic development of these abnormalities. A new classification schema correlates the embryologic, morphologic, and genetic bases of these anomalies in order to better distinguish and describe them. Although they provide a better understanding of the clinical aspects and genetics of these disorders, it is crucial for the radiologist to be able to diagnose the congenital posterior fossa anomalies based on their morphology, since neuroimaging is usually the initial step when these disorders are suspected. We divide the most common posterior fossa congenital anomalies into two groups: 1) hindbrain malformations, including diseases with cerebellar or vermian agenesis, aplasia or hypoplasia and cystic posterior fossa anomalies; and 2) cranial vault malformations. In addition, we will review the embryologic development of the posterior fossa and, from the perspective of embryonic development, will describe the imaging appearance of congenital posterior fossa anomalies. Knowledge of the developmental bases of these malformations facilitates detection of the morphological changes identified on imaging, allowing accurate differentiation and diagnosis of congenital posterior fossa anomalies., (© The Author(s) 2015.)
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- 2015
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20. Characterization of samhd1 morphant zebrafish recapitulates features of the human type I interferonopathy Aicardi-Goutières syndrome.
- Author
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Kasher PR, Jenkinson EM, Briolat V, Gent D, Morrissey C, Zeef LA, Rice GI, Levraud JP, and Crow YJ
- Subjects
- Acid Anhydride Hydrolases metabolism, Adenosine Deaminase genetics, Adenosine Deaminase metabolism, Amino Acid Sequence, Animals, Animals, Genetically Modified, Autoimmune Diseases of the Nervous System embryology, Autoimmune Diseases of the Nervous System metabolism, Blotting, Western, Cerebral Ventricles abnormalities, Cerebral Ventricles metabolism, Disease Models, Animal, Gene Expression Regulation, Developmental, Humans, Immunity, Innate genetics, Interferon Type I metabolism, Interferons genetics, Interferons metabolism, Intracranial Hemorrhages embryology, Intracranial Hemorrhages genetics, Intracranial Hemorrhages metabolism, Microscopy, Fluorescence, Molecular Sequence Data, Nervous System Malformations embryology, Nervous System Malformations metabolism, Reverse Transcriptase Polymerase Chain Reaction, Rhombencephalon abnormalities, Rhombencephalon metabolism, SAM Domain and HD Domain-Containing Protein 1, Sequence Homology, Amino Acid, Zebrafish embryology, Zebrafish genetics, Zebrafish metabolism, Zebrafish Proteins deficiency, Zebrafish Proteins metabolism, Acid Anhydride Hydrolases genetics, Autoimmune Diseases of the Nervous System genetics, Gene Knockdown Techniques, Interferon Type I genetics, Nervous System Malformations genetics, Zebrafish Proteins genetics
- Abstract
In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form of Aicardi-Goutières syndrome (AGS), an inherited inflammatory-mediated encephalopathy characterized by increased type I IFN activity and upregulation of IFN-stimulated genes (ISGs). In particular, SAMHD1-related AGS is associated with a distinctive cerebrovascular pathology that commonly leads to stroke. Although inflammatory responses are observed in immune cells cultured from Samhd1 null mouse models, these mice are physically healthy, specifically lacking a brain phenotype. We have investigated the use of zebrafish as an alternative system for generating a clinically relevant model of SAMHD1-related AGS. Using temporal gene knockdown of zebrafish samhd1, we observe hindbrain ventricular swelling and brain hemorrhage. Furthermore, loss of samhd1 or of another AGS-associated gene, adar, leads to a significant upregulation of innate immune-related genes and an increase in the number of cells expressing the zebrafish type I IFN ifnphi1. To our knowledge, this is the first example of an in vivo model of AGS that recapitulates features of both the innate immune and neurological characteristics of the disease. The phenotypes associated with loss of samhd1 and adar suggest a function of these genes in controlling innate immune processes conserved to zebrafish, thereby also contributing to our understanding of antiviral signaling in this model organism., (Copyright © 2015 by The American Association of Immunologists, Inc.)
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- 2015
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21. Update on neuroimaging phenotypes of mid-hindbrain malformations.
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Jissendi-Tchofo P, Severino M, Nguema-Edzang B, Toure C, Soto Ares G, and Barkovich AJ
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- Humans, Nervous System Malformations genetics, Nervous System Malformations pathology, Magnetic Resonance Imaging methods, Mesencephalon abnormalities, Mesencephalon pathology, Neuroimaging methods, Rhombencephalon abnormalities, Rhombencephalon pathology
- Abstract
Purpose: Neuroimaging techniques including structural magnetic resonance imaging (MRI) and functional positron emission tomography (PET) are useful in categorizing various midbrain-hindbrain (MHB) malformations, both in allowing diagnosis and in helping to understand the developmental processes that were disturbed. Brain imaging phenotypes of numerous malformations are characteristic features that help in guiding the genetic testing in case of direct neuroimaging-genotype correlation or, at least, to differentiate among MHB malformations entities. The present review aims to provide the reader with an update of the use of neuroimaging applications in the fine analysis of MHB malformations, using a comprehensive, recently proposed developmental and genetic classification., Methods: We have performed an extensive systematic review of the literature, from the embryology main steps of MHB development through the malformations entities, with regard to their molecular and genetic basis, conventional MRI features, and other neuroimaging characteristics., Results: We discuss disorders in which imaging features are distinctive and how these features reflect the structural and functional impairment of the brain., Conclusion: Recognition of specific MRI phenotypes, including advanced imaging features, is useful to recognize the MHB malformation entities, to suggest genetic investigations, and, eventually, to monitor the disease outcome after supportive therapies.
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- 2015
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22. Successfully treated symptomatic fusiform basilar artery aneurysm in a patient with hindbrain malformation via inverted Y-stenting.
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Purakal AS, Ginat DT, and Lee SK
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- Adult, Humans, Male, Rhombencephalon abnormalities, Rhombencephalon blood supply, Basilar Artery pathology, Cerebrovascular Circulation, Embolization, Therapeutic methods, Intracranial Aneurysm therapy, Rhombencephalon pathology, Stents, Vertebral Artery
- Abstract
A double overlapping reverse Y-stent approach to creating flow diversion using traditional open-cell stent technology was evaluated as a treatment option symptomatic fusiform basilar aneurysms. A 36-year-old man with a complex hindbrain malformation presented with acute ocular dysmotility due to a rapidly enlarging fusiform basilar artery aneurysm. The aneurysm was treated by insertion of two stents into the vertebrobasilar system in an inverted Y-configuration from the basilar tip to the V4 segments of the bilateral vertebral arteries, essentially creating flow diversion without using a dedicated flow diversion device. This resulted in immediate symptomatic improvement. The stents remained patent and the aneurysm was obliterated at 6 months follow-up. Furthermore, the patient remained free of associated symptoms at 10 months follow-up. Thus, the double stenting technique can be used instead of a flow diversion device to effectively create flow diversion, promote aneurysm sac thrombosis, and lead to resolution of symptoms in large fusiform basilar artery aneurysms., (2015 BMJ Publishing Group Ltd.)
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- 2015
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23. Medullary cap dysplasia: MRI and diffusion tensor imaging of a hindbrain malformation.
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Jurkiewicz E and Nowak K
- Subjects
- Child, Preschool, Diffusion Tensor Imaging, Humans, Magnetic Resonance Imaging, Male, Abnormalities, Multiple, Facial Asymmetry, Foot Deformities, Congenital, Hand Deformities, Congenital, Rhombencephalon abnormalities
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- 2015
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24. Hindbrain malformation and myoclonic seizures associated with a deleterious mutation in the INPP4A gene.
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Sheffer R, Bennett-Back O, Yaacov B, Edvardson S, Gomori M, Werner M, Fahham D, Anteby I, Frumkin A, Meiner V, and Elpeleg O
- Subjects
- Consanguinity, Humans, Male, Rhombencephalon physiopathology, Epilepsies, Myoclonic complications, Nervous System Malformations complications, Nervous System Malformations genetics, Nervous System Malformations physiopathology, Phosphoric Monoester Hydrolases genetics, Rhombencephalon abnormalities, Sequence Deletion
- Abstract
Hindbrain malformations with predominant cerebellar involvement have many causes including chromosomal disorders, specific genetic syndromes, and prenatal disruptions. The combination of a hindbrain malformation and myoclonic epilepsy is rare. Using exome sequencing in a consanguineous family, we identified a homozygous genomic deletion of 1770 bp within the INPP4A gene in a patient with myoclonic epilepsy, microcephaly, and atrophy of the inferior vermis and cerebellum. INPP4A participates in the excitatory glutamate signaling pathway and is essential for the degradation of phosphatidylinositol (3,4)-bisphosphate. Glutamatergic signaling is important for hindbrain development and is implicated in the pathogenesis of epilepsy, as well as excitotoxic cell death. Indeed, excessive glutamatergic stimulation was previously reported in INPP4A knockout mice. Our data adds a new etiology to the spectrum of hindbrain malformations in human, and when presented with myoclonic epilepsy may lead to the clinical suspicion of INPP4A defect. The present report further underscores the importance of phosphoinositides for the development of the inferior cerebellum and vermis.
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- 2015
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25. Re: Assessment of fetal midbrain and hindbrain in mid-sagittal cranial plane by three-dimensional multiplanar sonography.
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Garel C
- Subjects
- Humans, Ultrasonography, Cranial Fossa, Posterior abnormalities, Mesencephalon abnormalities, Mesencephalon diagnostic imaging, Nervous System Malformations diagnostic imaging, Nomograms, Rhombencephalon abnormalities, Rhombencephalon diagnostic imaging
- Published
- 2014
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26. Assessment of fetal midbrain and hindbrain in mid-sagittal cranial plane by three-dimensional multiplanar sonography. Part 2: application of nomograms to fetuses with posterior fossa malformations.
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Leibovitz Z, Shkolnik C, Haratz KK, Malinger G, Shapiro I, and Lerman-Sagie T
- Subjects
- Arnold-Chiari Malformation diagnostic imaging, Arnold-Chiari Malformation embryology, Arnold-Chiari Malformation pathology, Cerebellar Diseases diagnostic imaging, Cerebellar Diseases embryology, Cerebellar Diseases pathology, Dandy-Walker Syndrome diagnostic imaging, Dandy-Walker Syndrome embryology, Dandy-Walker Syndrome pathology, Humans, Imaging, Three-Dimensional, Mesencephalon diagnostic imaging, Mesencephalon embryology, Nomograms, Organ Size, Retrospective Studies, Rhombencephalon diagnostic imaging, Ultrasonography, Prenatal methods, Cranial Fossa, Posterior abnormalities, Mesencephalon abnormalities, Nervous System Malformations diagnostic imaging, Rhombencephalon abnormalities
- Abstract
Objectives: To apply fetal midbrain (MB) and hindbrain (HB) nomograms, developed using three-dimensional multiplanar sonographic reconstruction (3D-MPR) in the mid-sagittal cranial plane, to fetuses with known posterior fossa malformations., Methods: In this retrospective study we examined sonographic volumes obtained by sagittal acquisition in 43 fetuses diagnosed with posterior fossa abnormalities and evaluated in the mid-sagittal cranial plane, using 3D-MPR, the following: MB parameters tectal length (TL) and anteroposterior midbrain diameter (APMD), and HB parameters anteroposterior pons diameter (APPD), superoinferior vermian diameter (SIVD) and anteroposterior vermian diameter (APVD). Fetuses were grouped, according to malformation, into eight categories: cobblestone malformation complex (CMC, n = 3), Chiari-II malformation (C-II, n = 7), pontocerebellar hypoplasia (PCH, n = 2), rhombencephalosynapsis (RES, n = 4), Dandy-Walker malformation (n = 8), vermian dysgenesis (VD, n = 7), persistent Blake's pouch cyst (n = 6) and megacisterna magna (n = 6). In each case and for each subgroup, the MB-HB biometric parameters and their z-scores were evaluated with reference to our new nomograms., Results: The new MB-HB nomograms were able to identify the brainstem and vermian anomalies and differentiate fetuses with MB-HB malformations from those with isolated enlarged posterior fossa cerebrospinal fluid spaces. Use of the nomograms enabled detection of an elongated tectum in fetuses with CMC, C-II and RES, and a flattened pontine belly in cases of CMC, PCH and VD. In the fetuses with VD, the nomograms enabled division into three distinctive groups: (1) those with small SIVD and APVD, (2) those with normal SIVD but small APVD, and (3) those with small SIVD but normal APVD., Conclusions: Application of our new reference data, that for the first time include the MB, enables accurate diagnosis of brain malformations affecting the MB and HB and makes possible novel characterization of previously described features of posterior fossa anomalies., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)
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- 2014
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27. Midbrain-hindbrain involvement in septo-optic dysplasia.
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Severino M, Allegri AE, Pistorio A, Roviglione B, Di Iorgi N, Maghnie M, and Rossi A
- Subjects
- Abnormalities, Multiple pathology, Adult, Child, Female, Humans, Male, Young Adult, Developmental Disabilities etiology, Mesencephalon abnormalities, Rhombencephalon abnormalities, Septo-Optic Dysplasia pathology
- Abstract
Background and Purpose: Midbrain-hindbrain involvement in septo-optic dysplasia has not been well described, despite reported mutations of genes regulating brain stem patterning. We aimed to describe midbrain-hindbrain involvement in patients with septo-optic dysplasia and to identify possible clinical-neuroimaging correlations., Materials and Methods: Using MR imaging, we categorized 38 patients (21 males) based on the presence (group A, 21 patients) or absence (group B, 17 patients) of visible brain stem anomalies. We measured height and anteroposterior diameter of midbrain, pons, and medulla, anteroposterior midbrain/pons diameter (M/P ratio), vermian height, and tegmento-vermian angle, and compared the results with 114 healthy age-matched controls. Furthermore, patients were subdivided based on the type of midline anomalies. The associations between clinical and neuroradiological features were investigated. Post hoc tests were corrected according to Bonferroni adjustment (pB)., Results: Patients with brain stem abnormalities had smaller anteroposterior pons diameter than controls (pB < .0001) and group B (pB = .012), higher M/P ratio than controls (pB < .0001) and group B (pB < .0001), and smaller anteroposterior medulla diameter (pB = .001), pontine height (pB = .00072), and vermian height (pB = .0009) than controls. Six of 21 patients in group A had thickened quadrigeminal plate, aqueductal stenosis, and hydrocephalus; 3 also had agenesis of the epithalamus. One patient had a short midbrain with long pons and large superior vermis. There was a statistically significant association between brain stem abnormalities and callosal dysgenesis (P = .011) and developmental delay (P = .035), respectively., Conclusion: Midbrain-hindbrain abnormalities are a significant, albeit underrecognized, component of the septo-optic dysplasia spectrum, and are significantly associated with developmental delay in affected patients., (© 2014 by American Journal of Neuroradiology.)
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- 2014
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28. Rhombencephalosynapsis as a cause of aqueductal stenosis: an under-recognized association in hydrocephalic children.
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Whitehead MT, Choudhri AF, Grimm J, and Nelson MD
- Subjects
- Adolescent, Agenesis of Corpus Callosum pathology, Cerebellar Nuclei abnormalities, Cerebellar Nuclei pathology, Cerebellum abnormalities, Cerebellum pathology, Child, Child, Preschool, Constriction, Pathologic etiology, Constriction, Pathologic pathology, Female, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Male, Pregnancy, Retrospective Studies, Septum Pellucidum abnormalities, Septum Pellucidum pathology, Tomography, X-Ray Computed, Young Adult, Cerebral Aqueduct pathology, Hydrocephalus complications, Rhombencephalon abnormalities, Rhombencephalon pathology
- Abstract
Background: Rhombencephalosynapsis is a rare genetic aberration characterized by variable vermian hypoplasia/aplasia in conjunction with united cerebellar hemispheres. Genetic defects in the isthmic organizer at the mesencephalic-metencephalic junction are presumably responsible for the associated aqueductal stenosis., Objective: We performed a retrospective review of 20 children with rhombencephalosynapsis to evaluate for and emphasize the association of aqueductal stenosis and hydrocephalus., Materials and Methods: We retrospectively reviewed the MR and CT images of 20 children (0-11 years old) with rhombencephalosynapsis encountered at two academic children's hospitals. Rhombencephalosynapsis spectrum severity was graded based on pre-existing literature. We analyzed examinations for ventriculomegaly and degree of aqueductal stenosis. The collicular distances were measured from the collicular apices. Imaging studies were also analyzed for malformations of cortical and cerebellar development., Results: Thirteen of the 20 children (65%) with rhombencephalosynapsis presented with clinical or imaging evidence of hydrocephalus and aqueductal stenosis, principally involving the caudal cerebral aqueduct. All children with aqueductal stenosis had collicular fusion. All six children with complete rhombencephalosynapsis had aqueductal stenosis. The cerebral aqueduct varied from normal to stenotic in children with incomplete rhombencephalosynapsis. Corpus callosum dysgenesis was present in four children., Conclusion: Aqueductal stenosis in the setting of rhombencephalosynapsis is an under-recognized cause of noncommunicating hydrocephalus. Our findings support the hypothesis that a defect involving the common gene(s) responsible for the differentiation and development of both the roof plate and midline cerebellar primordium at the mesencephalon/first rhombomere junction may be responsible for the association of aqueductal stenosis and rhombencephalosynapsis.
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- 2014
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29. Mid-hindbrain malformations due to drugs taken during pregnancy.
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Merlini L, Fluss J, Dhouib A, Vargas MI, and Becker M
- Subjects
- Dermatologic Agents adverse effects, Female, Humans, Imaging, Three-Dimensional, Infant, Isotretinoin adverse effects, Magnetic Resonance Imaging, Male, Misoprostol adverse effects, Oxytocics adverse effects, Pregnancy, Rhombencephalon drug effects, Abnormalities, Drug-Induced pathology, Prenatal Exposure Delayed Effects pathology, Rhombencephalon abnormalities
- Abstract
Although genetic defects are the leading cause of central nervous system malformations including in the posterior fossa, specific malformative patterns should alert the clinician to consider rather a teratogenic etiology. We discuss the imaging features of 2 mid-hindbrain malformations consecutive to the intake of isotretinoin (Roaccuatane®; case 1) and misoprostol (Cytotec®; case 2) during pregnancy and review the pertinent literature. We correlate the morphological appearance of the mid-hindbrain malformation, as seen on high-resolution magnetic resonance imaging to possible drug-induced pathogenetical mechanisms. The recognition of characteristic imaging patterns enables diagnosis of and/or confirmation of suspected drug-induced hindbrain malformations. This has important medicolegal implications and also clinical significance to avoid unsuccessful and misleading genetic testing.
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- 2014
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30. Gómez-López-hernández syndrome versus rhombencephalosynapsis spectrum: a rare co-occurrence with bipartite parietal bone.
- Author
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Abdel-Salam GM, Abdel-Hadi S, Thomas MM, Eid OM, Ali MM, and Afifi HH
- Subjects
- Brain pathology, Facies, Humans, Infant, Magnetic Resonance Imaging, Male, Parietal Bone abnormalities, Skull abnormalities, Tomography, X-Ray Computed, Abnormalities, Multiple diagnosis, Alopecia diagnosis, Cerebellum abnormalities, Craniofacial Abnormalities diagnosis, Growth Disorders diagnosis, Neurocutaneous Syndromes diagnosis, Rhombencephalon abnormalities
- Abstract
Rhombencephalosynapsis (RES) is a rare hindbrain malformation that could occur in isolation or as a part of a syndrome for example, Gómez-López-Hernández syndrome (GLH) or VACTERL-H. We identified male patient with severe RES. Ventriculomegaly, agenesis of septum pellucidum, very thin corpus callosum with interhemispheric cyst were additional neuroimaging findings. He had brachyturricephaly, midface retrusion, low-set posteriorly rotated ears and bilateral parietal well circumscribed areas of alopecia. No corneal anesthesia was observed; thus, demonstrating many of the diagnostic criteria of GLH. Interestingly, he additionally had bilateral bipartite parietal bone (BPB) that is an extremely rare anomaly of the parietal sutures. This is the first co-occurrence of this rare anomaly with GLH. We believe the presence of this unique finding could represent an important clue for understanding the pathogenesis of this malformation., (© 2013 Wiley Periodicals, Inc.)
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- 2014
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31. Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11) deletion syndrome.
- Author
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Karpinski BA, Maynard TM, Fralish MS, Nuwayhid S, Zohn IE, Moody SA, and LaMantia AS
- Subjects
- Animals, Animals, Newborn, Body Patterning genetics, Craniofacial Abnormalities pathology, Craniofacial Abnormalities physiopathology, Deglutition, Deglutition Disorders genetics, Deglutition Disorders physiopathology, DiGeorge Syndrome, Disease Models, Animal, Embryo, Mammalian abnormalities, Embryo, Mammalian pathology, Feeding Behavior, Female, Gene Dosage, Gene Expression Regulation, Developmental, Male, Mice, Phenotype, Rhombencephalon abnormalities, Rhombencephalon embryology, Rhombencephalon pathology, Signal Transduction, T-Box Domain Proteins metabolism, Tretinoin metabolism, Chromosome Deletion, Cranial Nerves embryology, Cranial Nerves pathology, Deglutition Disorders embryology, Deglutition Disorders pathology
- Abstract
We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia--debilitating feeding, swallowing and nutrition difficulties from birth onward--within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA) signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V), glossopharyngeal (IX) or vagus (X) cranial nerves (CNs) that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS.
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- 2014
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32. Sema4d is required for the development of the hindbrain boundary and skeletal muscle in zebrafish.
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Yang J, Zeng Z, Wei J, Jiang L, Ma Q, Wu M, Huang X, Ye S, Li Y, Ma D, and Gao Q
- Subjects
- Animals, Antigens, CD genetics, Apoptosis genetics, Biomarkers metabolism, Embryo, Nonmammalian, Gene Knockdown Techniques, Muscle, Skeletal pathology, Myosins genetics, Myosins metabolism, Rhombencephalon abnormalities, Rhombencephalon pathology, Semaphorins genetics, Zebrafish genetics, Zebrafish Proteins genetics, Antigens, CD metabolism, Gene Expression Regulation, Developmental, Muscle, Skeletal embryology, Rhombencephalon embryology, Semaphorins metabolism, Zebrafish embryology, Zebrafish Proteins metabolism
- Abstract
Semaphorin4d (SEMA4D), also known as CD100, an oligodendrocyte secreted R-Ras GTPase-activating protein (GAP), affecting axonal growth is involved in a range of processes including cell adhesion, motility, angiogenesis, immune responses and tumour progression. However, its actual physiological mechanisms and its role in development remain unclear. This study has focused on the role of sema4d in the development and expression patterns in zebrafish embryos and the effect of its suppression on development using sema4d-specific antisense morpholino-oligonucleotides. In this study the knockdown of sema4d, expressed at all developmental stages, lead to defects in the hindbrain and trunk structure of zebrafish embryos. In addition, these phenotypes appeared to be associated with the abnormal expression of three hindbrain rhombomere boundary markers, wnt1, epha4a and foxb1.2, and two myogenic regulatory factors, myod and myog. Further, a notable increase of cell apoptosis appeared in the sema4d knockdown embryos, while no obvious reduction in cell proliferation was observed. Collectively, these data suggest that sema4d plays an important role in the development of the hindbrain and skeletal muscle., (Copyright © 2013 Elsevier Inc. All rights reserved.)
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- 2013
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33. Midbrain and hindbrain malformations: advances in clinical diagnosis, imaging, and genetics.
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Doherty D, Millen KJ, and Barkovich AJ
- Subjects
- Animals, Humans, Diagnostic Imaging trends, Mesencephalon abnormalities, Mesencephalon pathology, Rhombencephalon abnormalities, Rhombencephalon pathology
- Abstract
Historically, the midbrain and hindbrain have been considered of secondary importance to the cerebrum, which has typically been acknowledged as the most important part of the brain. In the past, radiologists and pathologists did not regularly examine these structures-also known as the brainstem and cerebellum-because they are small and difficult to remove without damage. With recent developments in neuroimaging, neuropathology, and neurogenetics, many developmental disorders of the midbrain and hindbrain have emerged as causes of neurodevelopmental dysfunction. These research advances may change the way in which we treat these patients in the future and will enhance the clinical acumen of the practising neurologist and thereby improve the diagnosis and treatment of these patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2013
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34. Rhombencephalosynapsis: embryopathology and management strategies of associated neurosurgical conditions with a review of the literature.
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Weaver J, Manjila S, Bahuleyan B, Bangert BA, and Cohen AR
- Subjects
- Adolescent, Arnold-Chiari Malformation complications, Brain Diseases diagnosis, Brain Diseases therapy, Cerebellum abnormalities, Child, Child, Preschool, Female, Humans, Hydrocephalus complications, Hydrocephalus surgery, Intellectual Disability etiology, Magnetic Resonance Imaging, Male, Nervous System Malformations therapy, Third Ventricle pathology, Third Ventricle surgery, Ventriculoperitoneal Shunt, Brain Diseases pathology, Cranial Fossa, Anterior abnormalities, Nervous System Malformations pathology, Rhombencephalon abnormalities, Rhombencephalon pathology
- Abstract
Object: Rhombencephalosynapsis (RS) is a rare congenital posterior fossa malformation characterized by dorsal fusion of the cerebellar hemispheres, hypogenesis or agenesis of the vermis, and fusion of the dentate nuclei and superior cerebellar peduncles. The objective of this institutional study is to review the clinical conditions associated with RS and analyze the varied biological profile of this unique condition., Methods: The study data were collected retrospectively from the medical records of patients at Rainbow Babies and Children's Hospital. After required institutional review board approval, the authors obtained information regarding the cases of RS reviewed by the Departments of Radiology, Genetics, and/or Pediatric Neurology. Medical charts were systematically reviewed, and 9 patients were analyzed in detail., Results: The authors describe 6 cases of RS and 3 cases of partial RS. This case series demonstrates an association between RS and symptomatic hydrocephalus (7 of 9 patients) and RS and Chiari malformation (5 of 9 patients). Patients with symptomatic hydrocephalus underwent endoscopic third ventriculostomy or ventriculoperitoneal shunt insertion. One of the patients with an associated Chiari malformation underwent foramen magnum decompression., Conclusions: The authors present a large case series of RS. Patients with RS often had hydrocephalus and/or a Chiari Type I or II hindbrain malformation. Neuroimaging findings of RS are presented along with hypotheses to explain the embryopathology of this unusual condition.
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- 2013
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35. Bilateral posterior periventricular nodular heterotopia: a recognizable cortical malformation with a spectrum of associated brain abnormalities.
- Author
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Mandelstam SA, Leventer RJ, Sandow A, McGillivray G, van Kogelenberg M, Guerrini R, Robertson S, Berkovic SF, Jackson GD, and Scheffer IE
- Subjects
- Adolescent, Adult, Aged, Cerebral Cortex abnormalities, Child, Child, Preschool, Cohort Studies, Contractile Proteins genetics, Corpus Callosum pathology, Female, Fetal Diseases genetics, Fetal Diseases pathology, Filamins, Hippocampus abnormalities, Humans, Infant, Infant, Newborn, Lateral Ventricles pathology, Male, Microfilament Proteins genetics, Middle Aged, Periventricular Nodular Heterotopia genetics, Pregnancy, Rhombencephalon abnormalities, Siblings, Twins, Monozygotic, Young Adult, Brain Diseases pathology, Lateral Ventricles abnormalities, Magnetic Resonance Imaging, Malformations of Cortical Development pathology, Periventricular Nodular Heterotopia pathology
- Abstract
Background and Purpose: Bilateral posterior PNH is a distinctive complex malformation with imaging features distinguishing it from classic bilateral PNH associated with FLNA mutations. The purpose of this study was to define the imaging features of posterior bilateral periventricular nodular heterotopia and to determine whether associated brain malformations suggest specific subcategories., Materials and Methods: We identified a cohort of 50 patients (31 females; mean age, 13 years) with bilateral posterior PNH and systematically reviewed and documented associated MR imaging abnormalities. Patients were negative for mutations of FLNA., Results: Nodules were often noncontiguous (n = 28) and asymmetric (n = 31). All except 1 patient showed associated developmental brain abnormalities involving a spectrum of posterior structures. A range of posterior fossa abnormalities affected the cerebellum, including cerebellar malformations and posterior fossa cysts (n = 38). Corpus callosum abnormalities (n = 40) ranged from mild dysplasia to agenesis. Posterior white matter volume was decreased (n = 22), and colpocephaly was frequent (n = 26). Most (n = 40) had associated cortical abnormalities ranging from minor to major (polymicrogyria), typically located in the cortex overlying the PNH. Abnormal Sylvian fissure morphology was common (n = 27), and hippocampal abnormalities were frequent (n = 37). Four family cases were identified-2 with concordant malformation patterns and 2 with discordant malformation patterns., Conclusions: The associations of bilateral posterior PNH encompass a range of abnormalities involving brain structures inferior to the Sylvian fissures. We were unable to identify specific subgroups and therefore conceptualize bilateral posterior PNH as a continuum of infrasylvian malformations involving the posterior cerebral and hindbrain structures.
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- 2013
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36. Chiari malformation type I: a case-control association study of 58 developmental genes.
- Author
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Urbizu A, Toma C, Poca MA, Sahuquillo J, Cuenca-León E, Cormand B, and Macaya A
- Subjects
- Adult, Aldehyde Dehydrogenase 1 Family, Arnold-Chiari Malformation metabolism, Arnold-Chiari Malformation pathology, Case-Control Studies, Cranial Fossa, Posterior abnormalities, Cranial Fossa, Posterior growth & development, Female, Gene Expression Profiling, Genome-Wide Association Study, Haplotypes, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Retinal Dehydrogenase genetics, Retinal Dehydrogenase metabolism, Rhombencephalon abnormalities, Rhombencephalon growth & development, Risk, Somites abnormalities, Somites growth & development, Arnold-Chiari Malformation genetics, Cranial Fossa, Posterior metabolism, Gene Expression Regulation, Developmental, Genes, Developmental, Morphogenesis genetics, Rhombencephalon metabolism, Somites metabolism
- Abstract
Chiari malformation type I (CMI) is a disorder characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa (PCF), often causing progressive neurological symptoms. The etiology of CMI remains unclear and is most likely multifactorial. A putative genetic contribution to CMI is suggested by familial aggregation and twin studies. Experimental models and human morphometric studies have suggested an underlying paraxial mesoderm insufficiency. We performed a case-control association study of 303 tag single nucleotide polymorphisms (SNP) across 58 candidate genes involved in early paraxial mesoderm development in a sample of 415 CMI patients and 524 sex-matched controls. A subgroup of patients diagnosed with classical, small-PCF CMI by means of MRI-based PCF morphometry (n = 186), underwent additional analysis. The genes selected are involved in signalling gradients occurring during segmental patterning of the occipital somites (FGF8, Wnt, and retinoic acid pathways and from bone morphogenetic proteins or BMP, Notch, Cdx and Hox pathways) or in placental angiogenesis, sclerotome development or CMI-associated syndromes. Single-marker analysis identified nominal associations with 18 SNPs in 14 genes (CDX1, FLT1, RARG, NKD2, MSGN1, RBPJ1, FGFR1, RDH10, NOG, RARA, LFNG, KDR, ALDH1A2, BMPR1A) considering the whole CMI sample. None of these overcame corrections for multiple comparisons, in contrast with four SNPs in CDX1, FLT1 and ALDH1A2 in the classical CMI group. Multiple marker analysis identified a risk haplotype for classical CMI in ALDH1A2 and CDX1. Furthermore, we analyzed the possible contributions of the most significantly associated SNPs to different PCF morphometric traits. These findings suggest that common variants in genes involved in somitogenesis and fetal vascular development may confer susceptibility to CMI.
- Published
- 2013
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37. Periventricular nodular heterotopia is related to severity of the hindbrain deformity in Chiari II malformation.
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Hino-Shishikura A, Niwa T, Aida N, Okabe T, Nagaoka T, and Shibasaki J
- Subjects
- Female, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging methods, Male, Arnold-Chiari Malformation complications, Arnold-Chiari Malformation pathology, Periventricular Nodular Heterotopia complications, Periventricular Nodular Heterotopia pathology, Rhombencephalon abnormalities
- Abstract
Background: Knowledge of the occurrence of malformations of cortical development (MCDs) and its relationship to hindbrain deformity in Chiari II malformation (CIIM) is limited., Objective: To assess malformations of cortical development and its relationship to hindbrain deformity regarding Chiari II malformation., Materials and Methods: Brain and cervical spinal MRI from 66 children (age range, 1-256 days; mean age, 22.3 days) with Chiari II malformation were retrospectively reviewed. If present, the type, number and location of malformations of cortical development were recorded. Hindbrain deformity was assessed for the level of the medullary kink, the descent of the pons and the shape of the fourth ventricle; these parameters were compared in children with and without malformations of cortical development., Results: Twenty children with malformations of cortical development were identified. Only periventricular nodular heterotopia was noted. The median level of the medullary kink was significantly lower in children with malformations of cortical development compared with children without it (P = 0.037). A low pontomesencephalic junction was identified more frequently in children with malformations of cortical development (65.0%), relative to children without malformations of cortical development (34.8%) (P = 0.045). The fourth ventricular shape was not significantly different in children with or without malformations of cortical development (P = 0.684)., Conclusion: Periventricular nodular heterotopia was seen in a relatively high proportion of children with Chiari II malformation, suggesting that it may be associated with severe hindbrain deformity.
- Published
- 2012
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38. Beyond Gómez-López-Hernández syndrome: recurring phenotypic themes in rhombencephalosynapsis.
- Author
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Tully HM, Dempsey JC, Ishak GE, Adam MP, Curry CJ, Sanchez-Lara P, Hunter A, Gripp KW, Allanson J, Cunniff C, Glass I, Millen KJ, Doherty D, and Dobyns WB
- Subjects
- Adolescent, Adult, Anal Canal abnormalities, Anal Canal pathology, Cerebellum abnormalities, Cerebellum pathology, Child, Child, Preschool, Esophagus abnormalities, Esophagus pathology, Female, Heart Defects, Congenital pathology, Holoprosencephaly pathology, Humans, Infant, Infant, Newborn, Kidney abnormalities, Kidney pathology, Limb Deformities, Congenital pathology, Male, Phenotype, Spine abnormalities, Spine pathology, Trachea abnormalities, Trachea pathology, Young Adult, Abnormalities, Multiple pathology, Alopecia pathology, Cerebellar Diseases pathology, Craniofacial Abnormalities pathology, Growth Disorders pathology, Neurocutaneous Syndromes pathology, Rhombencephalon abnormalities, Rhombencephalon pathology
- Abstract
Rhombencephalosynapsis (RES) is an uncommon cerebellar malformation characterized by fusion of the hemispheres without an intervening vermis. Frequently described in association with Gómez-López-Hernández syndrome, RES also occurs in conjunction with VACTERL features and with holoprosencephaly (HPE). We sought to determine the full phenotypic spectrum of RES in a large cohort of patients. Information was obtained through database review, patient questionnaire, radiographic, and morphologic assessment, and statistical analysis. We assessed 53 patients. Thirty-three had alopecia, 3 had trigeminal anesthesia, 14 had VACTERL features, and 2 had HPE with aventriculy. Specific craniofacial features were seen throughout the cohort, but were more common in patients with alopecia. We noted substantial overlap between groups. We conclude that although some distinct subgroups can be delineated, the overlapping features seen in our cohort suggest an underlying spectrum of RES-associated malformations rather than a collection of discrete syndromes., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
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39. Atoh1 governs the migration of postmitotic neurons that shape respiratory effectiveness at birth and chemoresponsiveness in adulthood.
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Huang WH, Tupal S, Huang TW, Ward CS, Neul JL, Klisch TJ, Gray PA, and Zoghbi HY
- Subjects
- Age Factors, Animals, Basic Helix-Loop-Helix Transcription Factors deficiency, Disease Models, Animal, Female, Humans, Infant, Newborn, Male, Mice, Mice, Knockout, Pregnancy, Respiratory Center physiopathology, Rhombencephalon physiopathology, Basic Helix-Loop-Helix Transcription Factors genetics, Cell Movement genetics, Respiratory Center abnormalities, Respiratory Physiological Phenomena genetics, Rhombencephalon abnormalities
- Abstract
Hindbrain neuronal networks serving respiratory, proprioceptive, and arousal functions share a developmental requirement for the bHLH transcription factor Atoh1. Loss of Atoh1 in mice results in respiratory failure and neonatal lethality; however, the neuronal identity and mechanism by which Atoh1-dependent cells sustain newborn breathing remains unknown. We uncovered that selective loss of Atoh1 from the postmitotic retrotrapezoid nucleus (RTN) neurons results in severely impaired inspiratory rhythm and pronounced neonatal death. Mice that escape neonatal death develop abnormal chemoresponsiveness as adults. Interestingly, the expression of Atoh1 in the RTN neurons is not required for their specification or maintenance, but is important for their proper localization and to establish essential connections with the preBötzinger Complex (preBötC). These results provide insights into the genetic regulation of neonatal breathing and shed light on the labile sites that might contribute to sudden death in newborn infants and altered chemoresponsiveness in adults., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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40. [Vitamin A deficiency causes asymmetric somitogenesis and abnormal hindbrain patterning in zebrafish embryos].
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Cao SS, Jia WS, and Zhao QS
- Subjects
- Animals, Embryonic Development genetics, Gene Knockout Techniques, Nervous System Malformations etiology, Nervous System Malformations genetics, Retinal Dehydrogenase genetics, Zebrafish genetics, Body Patterning genetics, Rhombencephalon abnormalities, Somites abnormalities, Vitamin A Deficiency complications, Zebrafish embryology
- Abstract
Retinoic acid (RA) plays essential roles in vertebrate embryogenesis. However, vertebrates cannot synthesize RA de novo. They synthesize it by two oxidative steps, first converting the precursor vitamin A into retinal by retinol dehydrogenase, and then oxidizing retinal into RA irreversibly by retinal dehydrogenase. It is known that vitamin A deficiency (VAD) causes Vitamin A Deficiency Syndrome in animals including quail, mouse, rat, and human. However, little is known about the effects of VAD on zebrafish embryogenesis. In this study, we obtained zebrafish VAD embryos from the zebrafish fed a retinoids-free diet. By analyzing the VAD embryos, we found that VAD caused asymmetric somitogenesis and abnormal hindbrain patterning in zebrafish embryos. However, the phenotype of defected hindbrain in VAD embryos was not as severe as that in the embryos in which aldh1a2, the major gene that is responsible for RA synthesis in zebrafish early development, was knocked down, or the embryos treated with 10 mmol/L DEAB (diethylaminobenzaldehyde, inhibitor of retinal dehydrogenases). Our results indicated that the VAD embryos were short of but not free of vitamin A, and they might also have a RA generation pathway independent of retinal dehydrogenase.
- Published
- 2012
41. Rhombencephalosynapsis: a hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity.
- Author
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Ishak GE, Dempsey JC, Shaw DW, Tully H, Adam MP, Sanchez-Lara PA, Glass I, Rue TC, Millen KJ, Dobyns WB, and Doherty D
- Subjects
- Adolescent, Adult, Cerebellum abnormalities, Cerebellum pathology, Child, Child, Preschool, Ectopia Cordis etiology, Female, Humans, Infant, Infant, Newborn, Male, Neuroimaging, Retrospective Studies, Rhombencephalon pathology, Severity of Illness Index, Young Adult, Abnormalities, Multiple, Alopecia complications, Craniofacial Abnormalities complications, Growth Disorders complications, Hydrocephalus complications, Mesencephalon pathology, Neurocutaneous Syndromes complications, Prosencephalon pathology, Rhombencephalon abnormalities
- Abstract
Rhombencephalosynapsis is a midline brain malformation characterized by missing cerebellar vermis with apparent fusion of the cerebellar hemispheres. Rhombencephalosynapsis can be seen in isolation or together with other central nervous system and extra-central nervous system malformations. Gómez-López-Hernández syndrome combines rhombencephalosynapsis with parietal/temporal alopecia and sometimes trigeminal anaesthesia, towering skull shape and dysmorphic features. Rhombencephalosynapsis can also be seen in patients with features of vertebral anomalies, anal atresia, cardiovascular anomalies, trachea-oesophageal fistula, renal anomalies, limb defects (VACTERL) association. Based on a comprehensive evaluation of neuroimaging findings in 42 patients with rhombencephalosynapsis, we propose a spectrum of severity, ranging from mild (the partial absence of nodulus, anterior and posterior vermis), to moderate (the absence of posterior vermis with some anterior vermis and nodulus present), to severe (the absence of posterior and anterior vermis with some nodulus present), to complete (the absence of the entire vermis including nodulus). We demonstrate that the severity of rhombencephalosynapsis correlates with fusion of the tonsils, as well as midbrain abnormalities including aqueductal stenosis and midline fusion of the tectum. Rhombencephalosynapsis is also associated with multiple forebrain abnormalities including absent olfactory bulbs, dysgenesis of the corpus callosum, absent septum pellucidum and, in rare patients, atypical forms of holoprosencephaly. The frequent association between rhombencephalosynapsis and aqueductal stenosis prompted us to evaluate brain magnetic resonance images in other patients with aqueductal stenosis at our institution, and remarkably, we identified rhombencephalosynapsis in 9%. Strikingly, subjects with more severe rhombencephalosynapsis have more severely abnormal neurodevelopmental outcome, as do subjects with holoprosencephaly and patients with VACTERL features. In summary, our data provide improved diagnostic and prognostic information, and support disruption of dorsal-ventral patterning as a mechanism underlying rhombencephalosynapsis.
- Published
- 2012
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42. Rhombencephalosynapsis: new findings in a larger study.
- Author
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Barth PG
- Subjects
- Cerebellum abnormalities, Female, Humans, Male, Abnormalities, Multiple, Alopecia complications, Craniofacial Abnormalities complications, Growth Disorders complications, Hydrocephalus complications, Mesencephalon pathology, Neurocutaneous Syndromes complications, Prosencephalon pathology, Rhombencephalon abnormalities
- Published
- 2012
- Full Text
- View/download PDF
43. Partial rhombencephalosynapsis and Chiari type II malformation in a child: a true association supported by DTI tractography.
- Author
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Merlini L, Fluss J, Korff C, and Hanquinet S
- Subjects
- Adolescent, Arnold-Chiari Malformation complications, Arnold-Chiari Malformation diagnosis, Epilepsy, Complex Partial diagnosis, Epilepsy, Complex Partial etiology, Epilepsy, Complex Partial pathology, Humans, Male, Nervous System Malformations diagnosis, Nervous System Malformations etiology, Arnold-Chiari Malformation pathology, Diffusion Tensor Imaging methods, Nervous System Malformations pathology, Rhombencephalon abnormalities, Rhombencephalon pathology
- Abstract
Partial rhombencephalosynapsis (PRECS) has been recently reported in association with Chiari II (CII). However, its existence as a true malformation is challenged due to the anatomical changes potentially induced by CII. The aim of this report was to investigate the contribution of midbrain/hindbrain tractography in this setting. A 13-year-old boy with a known CII malformation and operated myelomeningocele was referred for brain imaging after a first complex partial seizure. In addition to the classical features of CII, MRI showed partially fused cerebellar hemispheres and multiple supratentorial abnormalities. Diffusion tensor imaging (DTI) color map and tractography showed absent transverse fibers on the midsection of the cerebellum, scarce fibers of the middle cerebellar peduncle (MCP), absence of the middle pontine crossing tract, and fibers running vertically in the medial part of the cerebellum. Vertical mediocerebellar fibers are a feature of classical RECS and the paucity or absence of MCP fibers is mainly described in CII. In our patient, DTI and FT therefore demonstrated structural characteristics of both RECS and CII confirming their potential coexistence and suggesting possible shared embryological pathway.
- Published
- 2012
- Full Text
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44. Risk factors of sudden death in young adult patients with myelomeningocele.
- Author
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Jernigan SC, Berry JG, Graham DA, Bauer SB, Karlin LI, Hobbs NM, Scott RM, and Warf BC
- Subjects
- Adult, Age Factors, Analysis of Variance, Body Mass Index, Cohort Studies, Epilepsy complications, Epilepsy epidemiology, Female, Heart Diseases complications, Heart Diseases epidemiology, Humans, Kidney Diseases complications, Kidney Diseases epidemiology, Magnetic Resonance Imaging, Male, Meningomyelocele pathology, Mesencephalon pathology, Respiratory Tract Diseases complications, Respiratory Tract Diseases epidemiology, Rhombencephalon abnormalities, Risk Factors, Scoliosis complications, Scoliosis epidemiology, Sex Factors, Sleep Apnea, Central complications, Sleep Apnea, Central epidemiology, Treatment Outcome, Ventriculoperitoneal Shunt, Young Adult, Death, Sudden epidemiology, Death, Sudden etiology, Meningomyelocele mortality
- Abstract
Object: Although survival for patients with myelomeningocele has dramatically improved in recent decades, the occasional occurrence of sudden, unexplained death in young adult patients with myelomeningocele has been noted by the authors. This study was undertaken to determine risk factors for sudden death in this population., Methods: The authors performed a retrospective chart review of patients born between 1978 and 1990 who received care at Children's Hospital Boston. The relationship between sudden death and patient demographics, presence of CSF shunt and history of shunt revisions, midbrain length as a marker for severity of hindbrain malformation, seizures, pulmonary and ventilatory dysfunction, body mass index, scoliosis, renal dysfunction, and cardiac disease was evaluated using the t-test, Fisher exact test, and logistic regression analysis., Results: The age range for 106 patients in the study cohort was 19-30 years, with 58 (54.7%) women and 48 (45.3%) men. Six patients, all of whom were young women, experienced sudden death. In multivariate analysis, female sex, sleep apnea, and midbrain elongation ≥ 15 mm on MR imaging remained significantly associated with a higher risk of sudden death. These risk factors were cumulative, and female patients with sleep apnea and midbrain length ≥ 15 mm had the greatest risk (adjusted risk ratio 24.0, 95% CI 7.3-79.0; p < 0.05). No other comorbidities were found to significantly increase the risk of sudden death., Conclusions: Young adult women with myelomeningocele are at significantly increased risk of sudden death in the setting of midbrain elongation and sleep apnea. Further investigation is needed to determine the benefit of routine screening to identify at-risk patients for closer cardiopulmonary monitoring and treatment.
- Published
- 2012
- Full Text
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45. Basic genetic principles applied to posterior fossa malformations.
- Author
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Nunes RH, Littig IA, da Rocha AJ, and Vedolin L
- Subjects
- Cranial Fossa, Posterior embryology, Female, Gene Expression Regulation, Developmental, Genes, Developmental genetics, Genes, Developmental physiology, Humans, Infant, Newborn, Male, Nervous System Malformations genetics, Neuroimaging trends, Rhombencephalon embryology, Rhombencephalon growth & development, Sensitivity and Specificity, Cranial Fossa, Posterior abnormalities, Nervous System Malformations diagnosis, Neuroimaging methods, Rhombencephalon abnormalities
- Abstract
Recent advances in neuroimaging techniques turned possible for neuroradiologists to be frequently the first one to detect possible brain structural anomalies. However, with all the recent advances in genetics and embryology, understanding posterior fossa malformation's principles is being hardest to be achieved than previously. Studies in vertebrate models provide a developmental framework in which to categorize human hindbrain malformations and serve to inform our thinking regarding candidate genes involved in disrupted developmental processes. The main focus of this review was to survey the basic principles of the rhombomere division, anteroposterior and dorsoventral patterning, alar and basal zone concept, and axonal path finding to integrate the knowledge of human hindbrain malformations for better understanding the genetic basis of hindbrain development.
- Published
- 2011
- Full Text
- View/download PDF
46. Neuroimaging of Dandy-Walker malformation: new concepts.
- Author
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Correa GG, Amaral LF, and Vedolin LM
- Subjects
- Abnormalities, Multiple genetics, Cerebellum abnormalities, Cranial Fossa, Posterior parasitology, Dandy-Walker Syndrome genetics, Female, Fetal Diseases diagnosis, Genetic Counseling, Humans, Hydrocephalus diagnosis, Infant, Newborn, Male, Pregnancy, Rhombencephalon abnormalities, Abnormalities, Multiple diagnosis, Cranial Fossa, Posterior abnormalities, Dandy-Walker Syndrome diagnosis, Magnetic Resonance Imaging methods, Neuroimaging methods, Prenatal Diagnosis methods
- Abstract
Dandy-Walker malformation (DWM) is the most common human cerebellar malformation, characterized by hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and an enlarged posterior fossa with upward displacement of the lateral sinuses, tentorium, and torcular. Although its pathogenesis is not completely understood, there are several genetic loci related to DWM as well as syndromic malformations and congenital infections. Dandy-Walker malformation is associated with other central nervous system abnormalities, including dysgenesis of corpus callosum, ectopic brain tissue, holoprosencephaly, and neural tube defects. Hydrocephalus plays an important role in the development of symptoms and neurological outcome in patients with DWM, and the aim of surgical treatment is usually the control of hydrocephalus and the posterior fossa cyst. Imaging modalities, especially magnetic resonance imaging, are crucial for the diagnosis of DWM and distinguishing this disorder from other cystic posterior fossa lesions. Persistent Blake's cyst is seen as a retrocerebellar fluid collection with cerebrospinal fluid signal intensity and a median line communication with the fourth ventricle, commonly associated with hydrocephalus. Mega cisterna magna presents as an extraaxial fluid collection posteroinferior to an intact cerebellum. Retrocerebellar arachnoid cysts frequently compress the cerebellar hemispheres and the fourth ventricle. Patients with DWM show an enlarged posterior fossa filled with a cystic structure that communicates freely with the fourth ventricle and hypoplastic vermis. Comprehension of hindbrain embryology is of utmost importance for understanding the cerebellar malformations, including DWM, and other related entities.
- Published
- 2011
- Full Text
- View/download PDF
47. ZIC2 mutations are seen in holoprosencephaly and not partial rhombencephalosynapsis.
- Author
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Guleria S
- Subjects
- Female, Humans, Male, Holoprosencephaly genetics, Mutation genetics, Nuclear Proteins genetics, Rhombencephalon abnormalities, Rhombencephalon pathology, Transcription Factors genetics
- Published
- 2011
- Full Text
- View/download PDF
48. Prevalence and timing of pregnancy termination for brain malformations.
- Author
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Rouleau C, Gasner A, Bigi N, Couture A, Perez MJ, Blanchet P, Faure JM, Rivier F, Boulot P, Laquerrière A, and Encha-Razavi F
- Subjects
- Abortion, Induced methods, Acrocallosal Syndrome diagnostic imaging, Acrocallosal Syndrome epidemiology, Acrocallosal Syndrome surgery, Brain embryology, Echoencephalography methods, Female, Fetal Development, Fetal Diseases diagnostic imaging, Fetal Diseases surgery, France epidemiology, Gestational Age, Humans, Neural Tube Defects diagnostic imaging, Neural Tube Defects epidemiology, Neural Tube Defects surgery, Pregnancy, Retrospective Studies, Rhombencephalon abnormalities, Rhombencephalon diagnostic imaging, Ultrasonography, Prenatal, Abortion, Induced statistics & numerical data, Brain abnormalities, Fetal Diseases epidemiology
- Abstract
Objective: To determine the prevalence and the timing of pregnancy termination relative to the type of central nervous system (CNS) malformations. Design Retrospective cohort study., Setting: Multidisciplinary centre for prenatal diagnosis in the Languedoc-Roussillon region, France., Population: A cohort of 481 pregnancy terminations performed between 2005 and 2009., Methods: Detailed post-termination fetal and neuropathological analyses were carried out to identify the CNS malformations. Then, the prevalence and timing of pregnancy termination were assessed relative to the identified malformations., Results: About one-third of pregnancy terminations (143/481) were performed for severe CNS malformations. Up to 24 weeks of gestation (WG), pregnancy terminations (56.6%) were carried out mainly for defects occurring during the two major first steps of CNS development (neurulation and differentiation of cerebral vesicles). After 24 WG, pregnancy terminations (43.3%) were mainly performed for corpus callosum agenesis (16/17), vermian agenesis (10/12) and gyral anomalies (13/15). For hindbrain malformations and gyral anomalies, there was a significant relationship between the timing of pregnancy termination and the presence of a severe ventriculomegaly at prenatal diagnosis (p=0.002 and p=0.02, respectively)., Conclusion: By classifying CNS malformations according to the neuropathological analysis, the authors show that the timing and prevalence of pregnancy termination are distributed in a manner that is consistent with what is currently known on the development of brain. They are also influenced by the French prenatal screening policy and the variable expressivity of the brain malformations and associated lesions.
- Published
- 2011
- Full Text
- View/download PDF
49. Recurrent partial rhombencephalosynapsis and holoprosencephaly in siblings with a mutation of ZIC2.
- Author
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Ramocki MB, Scaglia F, Stankiewicz P, Belmont JW, Jones JY, and Clark GD
- Subjects
- Adolescent, Child, Child, Preschool, Chromosome Banding, Comparative Genomic Hybridization, Female, Holoprosencephaly diagnosis, Humans, Infant, Male, Siblings, Holoprosencephaly genetics, Mutation genetics, Nuclear Proteins genetics, Rhombencephalon abnormalities, Rhombencephalon pathology, Transcription Factors genetics
- Abstract
Rhombencephalosynapsis (RES) is a rare congenital brain malformation typically identified by magnetic resonance imaging and characterized by fusion of the cerebellar hemispheres and dentate nuclei and vermian agenesis or hypogenesis. Although RES is frequently found in conjunction with other brain malformations and/or congenital anomalies, no specific molecular etiology has been discovered to date and no animal models exist. We identified two half sisters with alobar or semi-lobar holoprosencephaly (HPE) and partial RES, suggesting that genes linked to HPE may also contribute to RES. A deletion of seven base pairs in exon one of the ZIC2 gene (c.392_98del7) was identified in each of the two half sisters with HPE and partial RES. To identify genetic causes of RES and to assess whether genes identified in HPE have a role in RES, we tested 11 additional individuals with RES by high-resolution chromosome analysis, chromosomal microarray analysis, and sequencing of four HPE genes. No mutations in ZIC2 or in other genes that cause HPE were identified, suggesting that mutation of ZIC2 is a rare cause of, or contributor to, RES associated with HPE. In addition, an individual with a complex rearrangement of chromosome 22q13.3 and RES was identified, suggesting the presence of a dosage-sensitive gene that may contribute to RES in this region., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
- Full Text
- View/download PDF
50. Partial rhombencephalosynapsis: prenatal MR imaging diagnosis and postnatal follow up.
- Author
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Koprivsek KM, Novakov-Mikic AS, Lucic MA, Kozic DB, Till VE, and Belopavlovic Z
- Subjects
- Adult, Diseases in Twins, Female, Gravidity, Humans, Longitudinal Studies, Pregnancy, Magnetic Resonance Imaging methods, Prenatal Diagnosis methods, Rhombencephalon abnormalities, Rhombencephalon pathology
- Abstract
We present a case of partial rhombencephalosynapsis, diagnosed by magnetic resonance imaging (MRI), in fetus aged 27 gestational weeks, in a dizygotic twin pregnancy. The distinctive MRI features of this cerebellar malformation (segmental hypogenesis of the cerebellar vermis, partial fusion of the cerebellar hemispheres and dentate nuclei) without associated cerebral abnormalities were confirmed by 32-weeks prenatal and 3-months postnatal MRI studies. At the age of 12 months the affected twin had a slight delay in psychomotor development, mild hypotonia with normal cognitive development. To the authors' best knowledge, this is the first report of a fetal case with isolated partial rhombencephalosynapsis. Its MRI features enlarges the narrow spectrum of uncommon variants of rhombencephalosynapsis, and allow an accurate differentiation from other vermian and cerebellar anomalies with less favorable postnatal outcome.
- Published
- 2011
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