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Objectives When identified prenatally, the imaging triad of asymmetric ventriculomegaly, interhemispheric cyst, and dysgenesis of the corpus callosum (AVID) can indicate a more serious congenital brain anomaly. In this follow-up series of 15 fetuses, we present the neurodevelopmental outcomes of a single institution cohort of children diagnosed prenatally with AVID. Methods Our fetal ultrasound database was queried for cases of AVID between 2000 and 2016. All available fetal MR imaging studies were reviewed for the presence of (a) interhemispheric cysts or ventricular diverticula and (b) dysgenesis or agenesis of the corpus callosum. Clinical records were reviewed for perinatal management, postnatal surgical management, and neurodevelopmental outcomes. Results Fifteen prenatal cases of AVID were identified. Twelve were live-born and three pregnancies were terminated. Of the 12 patients, 11 underwent neurosurgical intervention. Of the eight patients surviving past infancy, seven of eight have moderate to severe neurodevelopmental delays or disabilities, encompassing both motor and language skills, and all have variable visual abnormalities. Conclusion In our cohort of 15 prenatally diagnosed fetuses with AVID, eight survived past infancy and all have neurodevelopmental disabilities, including motor and language deficits, a wide range of visual defects, craniofacial abnormalities, and medical comorbidities.

Background/Aims: Thyroid disease is a common comorbidity in individuals with Down syndrome (DS), but historical studies have multiple limitations. We assessed thyroid abnormalities in a large cohort of children with DS. Methods: Retrospective records review from a single institution. Calculated prevalence of common thyroid abnormalities and associations with common comorbidities. Results: Among 508 patients, 120 (24%) had a thyroid-related diagnosis, the majority having elevated thyrotropin treated with levothyroxine. A Kaplan-Meier estimate projects that 50% have thyroid disorder by adulthood, with 20% of hypothyroidism diagnosed before the age of 6 months. When tested, approximately 50% had positive antithyroid antibodies, though this rate was 100% in overt hypothyroidism. There was no association between congenital or acquired hypothyroidism and common comorbidities. Conclusion: Thyroid disease in DS is more common and occurs earlier than in the general population, and is often transient. Thyroid disease is unrelated to gender, obesity, or other comorbidities. Apart from overt hypothyroidism, much of hypothyroidism in DS appears unrelated to autoimmunity; we recommend checking of antithyroid antibodies only in select cases. An additional screen for thyroid disease between the newborn screen and the 6-month well-child visit will detect early cases of hypothyroidism who passed their newborn screen.

CASE Isela is an 11-year-old Mexican-American girl with mild intellectual disability. During a vacation with her family, she went swimming with dolphins. A few days later, Isela awoke at night with laughing spells; during the day, she was pacing, aggressive, and had a decline in self-care and communication skills. Her parents attributed the symptoms to the dolphins. She was evaluated by a pediatric neurologist. The sleep-deprived electroencephalogram, brain magnetic resonance imaging, lumbar puncture, and thyroid function tests were normal. A genomic microarray was sent. The neurologist initiated empirical therapy for seizures with lamotrigine, which caused a rash. It was discontinued. She was then treated with oxcarbazepine followed by topiramate for several months without any change in symptoms. Comparative genomic hybridization revealed a small deletion at 14q13.1, which includes the NPAS3 gene. Psychiatry was consulted after several months of persistent symptoms. Isela seemed to be laughing in response to internal stimuli. Owing to the decline in communication and her apparent preoccupation with visual and auditory internal stimuli, Isela could not be interviewed adequately to confirm that she was experiencing hallucinations, but her laughter seemed to be in response to hallucinations. Isela was diagnosed with disorganized schizophrenia with psychosis. Risperidone was prescribed. A psychology evaluation was completed a few months later. Parents noted significant improvement after starting risperidone with reduced inappropriate laughing spells, reduced pacing, as well as improved eating, sleeping, communication, and self-care. Cognitive assessment with the Wechsler Abbreviated Scale of Intelligence-II indicated the following: verbal estimated intelligence quotient (IQ) = 70, perceptual estimated IQ = 71, and full-scale estimated IQ = 68. There was no cognitive decline compared with testing at school 4 years previously. Although psychotic symptoms were significantly improved on antipsychotic medication and function appeared to have been restored to her previous level, her parents continued to perceive a significant decline of functioning, and they continued to attribute the psychosis to swimming with the dolphins.

The functional, financial, and social impact on families of children with Down syndrome (DS) in the United States and the role of the US health care system in ameliorating these impacts have not been well characterized. We sought to describe the demographic characteristics and functional difficulties of these children and to determine whether children with DS, compared with children with "intellectual disability" (ID) generally, and compared with other "children and youth with special health care needs" (CYSHCN), are more or less likely to receive health care that meets quality standards related to care coordination and to have their health care service needs met.This study analyzed data from the 2005-2006 National Survey of Children with Special Health Care Needs (n = 40,723). Children and youth aged 0 to 17 years with special health care need (CYSHCN) who experience DS (n = 395) and/or IDs (n = 4252) were compared with each other and other CYSHCN on a range of functioning, family impact, and health care quality variables using bivariate and multivariate methods. Data were weighted to represent all CYSHCN in the United States.Compared with CYSHCN without DS, children with DS were significantly less likely to receive comprehensive care within a medical home (29.7% vs 47.3%; p.001). Parents of children with DS were also significantly more likely to cut back or stop work due to their child's health needs (23.5% vs 55.1%; p.001). Although overall system performance was poorer for children with DS compared with those with ID and no DS after adjustment for family income, prevalence on most aspects of quality of care and family impacts evaluated were similar for these 2 groups.In this study, the families of children with DS, and ID generally, are burdened disproportionately when compared with other CYSHCN, reflecting the combination of impairments intrinsic to DS and ID and impacts of suboptimal medical care coordination and social support.

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a result of a hemizygotic microdeletion that results in a variety of impairments in children including greater risk for psychiatric ailments in adulthood. We used high-resolution magnetic resonance imaging to accurately quantify the length and, for the first time, volume, of the cavum septum pellucidum (CSP) in children aged 7 to 14 years with 22q11.2DS and typically developing (TD) controls. Significantly greater anteroposterior length and greater CSP volumes were found in children with 22q11.2DS compared with controls. Furthermore, the largest CSP were found only in the 22q11.2DS group and with a much higher incidence than previously reported in the literature. Given the significant midline anomalies in the brains of those affected by 22q11.2DS, large CSP may be a biomarker of atypical brain development. The implication of these larger CSP for cognitive and behavioral development is a topic in need of further investigation.

Down syndrome is characterized by disproportionately severe impairments of speech and language, yet little is known about the neural underpinnings of these deficits. We compared fMRI activation patterns during passive story listening in 9 young adults with Down syndrome and 9 approximately age-matched, typically developing controls. The typically developing group exhibited greater activation than did the Down syndrome group in classical receptive language areas (superior and middle temporal gyri) for forward > backward speech; the Down syndrome group exhibited greater activation in cingulate gyrus, superior and inferior parietal lobules, and precuneus for both forward speech > rest and backward speech > rest. The Down syndrome group showed almost no difference in activation patterns between the language (forward speech) and nonlanguage (backward speech) conditions.

We report on a 16-month-old girl with developmental motor delay, microcephaly, and mild truncal ataxia who was revealed to have rhombencephalosynapsis on magnetic resonance imaging. The child was nonsyndromic and exhibited normal cognitive and social abilities for her age, despite neuroimaging findings. As this case demonstrates, motor skills in children with isolated rhombencephalosynapsis may be relatively mildly affected, and cognition may be normal despite the presence of a major central nervous system anomaly. Neuroimaging may be helpful in defining the nature of a child's deficits at an early age, particularly when associated with microcephaly and abnormalities on neurologic examination.

We report on a 5-year-old Caucasian female with multiple anomalies whose deletion, 46,XX,del(21)(q22.11q22.13), was determined by a 105K oligonucleotide-based microarray. This case is a unique deletion that mimicked Fanconi anemia (combination of thrombocytopenia, thumb anomalies, congenital heart defects, borderline small head circumference, strabismus, hydronephrosis, and significant developmental delay) but testing for Fanconi anemia was negative, as was testing for a wide array of genetic/metabolic conditions. Microarray testing done at 5 months failed to demonstrate the interstitial deletion that was found on a newer generation microarray test performed after 3 years of age. When compared to other reported cases of partial monosomy 21q, the unique features of this case include: (1) cleft palate, although high palate is reported in other cases; (2) neonatal thrombocytopenia requiring platelet transfusion; (3) a platelet function defect, reported previously as platelet storage pool defect as part of a familial platelet disorder; and (4) an immune function defect. Similar to other reported patients with terminal 21q deletion, this child had significant developmental delay, and feeding and growth problems. This case also highlights the ability for newer technology microarrays to identify small interstitial deletions previously missed by an earlier version microarray. The advances in the microarray technologies are allowing us to better define new phenotypes and leading to the identification of a diagnosis for many patients who have been previously undiagnosed. Review of the genes involved in these novel deletions allows the caring physician to design surveillance strategies that are custom-designed for these unique patients.

Joubert syndrome is an autosomal recessive disorder characterized by hypotonia, ataxia, developmental delay, and a distinctive hindbrain malformation involving the cerebellum and brain stem, visualized radiographically on magnetic resonance imaging (MRI) as the "molar tooth sign." In postmortem brains from subjects with Joubert syndrome, there is an apparent absence of decussation of both corticospinal and superior cerebellar tracts, although the functional significance has not been elucidated. We sought to explore the cerebral and cerebellar activation pattern elicited by finger tapping in an adolescent with Joubert syndrome and in a normal control subject using functional MRI. In contrast to the typical highly lateralized activation seen in our control subject, the subject with Joubert syndrome demonstrated striking bilateral activation of the sensorimotor and cerebellar cortex. Although our functional MRI data do not indicate a clear absence of decussation, the abnormal activation pattern observed suggests altered brain functional organization in relation to anatomic differences. Malformation of the hindbrain could result in recruitment of alternative pathways, similar to what has been observed following ischemic injury to the developing or mature central nervous system.

Intravenous immunoglobulin has been reported to be an effective treatment for infantile spasms. Juvenile spasms are electrically and clinically similar to infantile spasms but occur in a later age group. We retrospectively reviewed the charts of five children (aged 4.5—11.5 years) at our institution. Their primary seizure type was juvenile spasms and they were treated with a single inpatient course of intravenous immunoglobulin (400 mg/kg/day intravenously for 5 consecutive days) on an adjunctive basis. Seizure frequency was determined from parental reports. By 3 months after treatment, improvement (a 50—92% reduction in seizure frequency) was noted in four patients; sustained benefit was seen in three patients for up to 12 months. One patient showed no response at 3 and 6 months and had an increase in seizure frequency at 1 year. We conclude that single-course intravenous immunoglobulin can be effective as adjunctive therapy for juvenile spasms and that benefit can persist for many months. However, larger controlled, prospective clinical trials are needed to validate this unconventional treatment modality for specific seizure types such as juvenile spasms. ( J Child Neurol 2003;18:379—382).

Down's syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down's syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down's syndrome.Sixteen children and young adults with Down's syndrome (age range=5-23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition.Consistent with prior imaging studies, subjects with Down's syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down's syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down's syndrome subjects.The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down's syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down's syndrome.