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Background: X-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1. The high clinical and genetic heterogeneity of CDPX1 presents a challenge to prenatal diagnosis. Case presentation: A G1P0 woman in her 30s with an unremarkable prenatal course presented in the second trimester. Maternal diseases, tobacco, alcohol, and drug history during pregnancy were denied. Obstetrical ultrasound examination revealed a flattened nose and a flattened midface with echogenic alterations of lumbar spinous process in the fetus. Amniocentesis was performed for genetic testing. A normal karyotype and a negative result of CNV-seq were obtained. However, Whole exome sequencing (WES) in trios revealed a hemizygous ARSL variant [NM_000047.3:c.1108del p.(Trp370Glyfs*35)] in the fetus, which was maternally inherited as confirmed by Sanger sequencing. This variant was absent from the genomAD and HGMD databases. According to the ACMG guidelines, this variant was interpreted as likely pathogenic (PVS1 + PM2_Supporting). The couple decided to terminate the pregnancy. After induction of labour, a severe nasal hypoplasia was noted; and brachytelephalangy was not remarkable. Postmortem digital X-ray imaging revealed symmetrical stippled epiphyses of the vertebrae in all spine regions and enlargement of spinous process of L1-L4 vertebrae. Conclusion: A novel frameshift deletion variant of ARSL and the associated fetal phenotype have been identified. This study provides useful information for prenatal diagnosis and genetic counseling of CDPX1. [ABSTRACT FROM AUTHOR]

Abstract Background X-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1. The high clinical and genetic heterogeneity of CDPX1 presents a challenge to prenatal diagnosis. Case presentation A G1P0 woman in her 30s with an unremarkable prenatal course presented in the second trimester. Maternal diseases, tobacco, alcohol, and drug history during pregnancy were denied. Obstetrical ultrasound examination revealed a flattened nose and a flattened midface with echogenic alterations of lumbar spinous process in the fetus. Amniocentesis was performed for genetic testing. A normal karyotype and a negative result of CNV-seq were obtained. However, Whole exome sequencing (WES) in trios revealed a hemizygous ARSL variant [NM_000047.3:c.1108del p.(Trp370Glyfs*35)] in the fetus, which was maternally inherited as confirmed by Sanger sequencing. This variant was absent from the genomAD and HGMD databases. According to the ACMG guidelines, this variant was interpreted as likely pathogenic (PVS1 + PM2_Supporting). The couple decided to terminate the pregnancy. After induction of labour, a severe nasal hypoplasia was noted; and brachytelephalangy was not remarkable. Postmortem digital X-ray imaging revealed symmetrical stippled epiphyses of the vertebrae in all spine regions and enlargement of spinous process of L1-L4 vertebrae. Conclusion A novel frameshift deletion variant of ARSL and the associated fetal phenotype have been identified. This study provides useful information for prenatal diagnosis and genetic counseling of CDPX1.

Errors of cholesterol b i o s y n t h e s i s r e p r e s e n t a heterogeneous group of metabolic disorders. The aim of the authors of this article is to present a case of a patient with typical symptoms of a rare post-squalene disorder of cholesterol biosynthesis, its diagnostics and progress in neonatal period. The differential diagnosis of a typical findings on the skin wi th spontaneous r e g r e s s i o n i c h t y o s i f o rm erythroderma, craniofacial dysmorphic features, anomalies of organs or skeletal abnormalities in a newborn may also be the result of a di sorde r of chol e s t e rol biosynthesis. The final diagnosis is definitely confirmed by DNA analysis. Prognosis depends on the different enzyme defects of cholesterol biosynthesis pathway, but typically on the post-squalene pathway. Cholesterol is an important substance that plays a significant role in membrane structure, as well as being the precursor for the synthesis of the steroid hormones and bile acids. Cholesterol synthesis occurs in the cytoplasm and microsomes from the twocarbon acetate group of acetyl coenzyme A (acetyl-CoA). The biosynthesis of cholesterol consists of several reactions. Acetyl-CoA units are converted to mevalonate by a series of reactions. Mevalonate is formed on squalene and then lanosterol. Lanosterol is conver ted by two di fferent pathways, either with the creation of 7-dehydrocholesterol , or desmosterol with the creation of cholesterol. Errors of cholesterol biosynthesis represent a heterogeneous group of metabol ic disorders that is c h a r a c t e r i z e d b y mu l t i p l e dysmorphic features underlining an important role for cholesterol in human embryogene s i s and development. The differential diagnosis of atypical findings on the skin in newborn may be the result of d i s o r d e r o f c h o l e s t e r o l biosynthesis. It may be also associated with various dysmorphic features or anomalies including multiple anomalies of congenital and internal organs and skeletal abnormalities. Some of the postsqualene disorders may point to atypical findings on the skin in the form of psoriatic eruptions, psychomotoric delay or laboratory findings as hypocholesterolemia

Chondrodysplasia punctata (CDP) is a group of bone dysplasias characterized by punctate calcifications in the cartilage, mainly epiphyseal. Among the various forms of CDP, the X-linked form is rare and has been described in 50 male patients in the literature. The aim of this study is to describe an atypical case of CDPX1 and compare it with previous literature. Preschooler, male, four years old, born full-term, small for gestational age and with no similar cases in the family. He developed disproportionate short stature, eutrophy, cervical and dorsal scoliosis with pectus carinatum, slight asymmetry in the lower limbs, ocular hypertelorism with blue-gray sclera and hair loss. He did not present fractures or bone pain and had neuropsychomotor development appropriate for his age. The exams showed no changes in the osteometabolic profile or in pituitary hormones. The karyotype was 46,XY and the genetic panel for skeletal dysplasias showed a hemizygous pathogenic variant in the ARSL gene (Arylsulfatase L) chrX:2.934.859 C>T (p.Trp581* ENST00000381134) diagnosed with X-linked chondrodysplasia punctata type 1. CDPX1 is directly related to the deficiency of ARSL enzyme activity, which can result in changes in neuropsychomotor development, hearing loss and episodes of respiratory failure. However, these characteristics were not presented by the proband. Thus, the proband has a milder form of CDPX1. Early diagnosis of skeletal dysplasias such as CDPX1 is important for adequate outpatient follow-up, family counseling and prevention of the development of long-term comorbidities.

Abstract Background Obsessive–Compulsive Disorder (OCD) is a common and chronic psychiatric disorder with significant morbidity characterized by intrusive, uncontrollable and reoccurring thoughts (i.e., obsessions) and/or ritualistic behaviours (i.e., compulsions). Conradi-Hünerman-Happle Syndrome (CHHS) is a rare inherited X-linked dominant variant of chondrodysplasia punctata, a heterogeneous group of rare bone dysplasias characterized by punctate epiphyseal calcifications of complex etiology and pathophysiology that remain to be defined. Available literature reveals a lacuna in regards to the coexistence of the entities with no clinical reports described. Case presentation A 12 year old female patient with diagnosis of CHHS, presents to psychiatric consultation due to aggravation of her OCD clinical picture, with aggravation of hand-washing frequency during the Covid-19 pandemic with significant functional impact. Psychopharmacological treatment aimed at OCD with Selective Serotonin Reuptake Inhibitor (SSRI) and antipsychotic was instituted with favourable, albeit partial response. Conclusions The authors aim to describe a clinical case in which the patient presents with Conradi-Hünerman-Happle Syndrome and Obsessive–Compulsive Disorder. Clinical descriptions of CHHS and OCD are not available in the literature. Through this case description the authors aim to present a rare case as well as discuss an eventual association between etiology and/or pathophysiology of the two disorders.

Background: Obsessive–Compulsive Disorder (OCD) is a common and chronic psychiatric disorder with significant morbidity characterized by intrusive, uncontrollable and reoccurring thoughts (i.e., obsessions) and/or ritualistic behaviours (i.e., compulsions). Conradi-Hünerman-Happle Syndrome (CHHS) is a rare inherited X-linked dominant variant of chondrodysplasia punctata, a heterogeneous group of rare bone dysplasias characterized by punctate epiphyseal calcifications of complex etiology and pathophysiology that remain to be defined. Available literature reveals a lacuna in regards to the coexistence of the entities with no clinical reports described. Case presentation: A 12 year old female patient with diagnosis of CHHS, presents to psychiatric consultation due to aggravation of her OCD clinical picture, with aggravation of hand-washing frequency during the Covid-19 pandemic with significant functional impact. Psychopharmacological treatment aimed at OCD with Selective Serotonin Reuptake Inhibitor (SSRI) and antipsychotic was instituted with favourable, albeit partial response. Conclusions: The authors aim to describe a clinical case in which the patient presents with Conradi-Hünerman-Happle Syndrome and Obsessive–Compulsive Disorder. Clinical descriptions of CHHS and OCD are not available in the literature. Through this case description the authors aim to present a rare case as well as discuss an eventual association between etiology and/or pathophysiology of the two disorders. [ABSTRACT FROM AUTHOR]

Introduction: The skeletal dysplasias are a group of more than 450 heritable disorders of bone. They frequently present in the newborn period with disproportion, radiographic abnormalities, and occasionally other organ system abnormalities. Aims: To enumerate the radiological features of various types skeletal dysplasias. Materials and methods: It's a Prospective study conducted for a period of one year in patients referred from orthopedic and paediatric departments who were suspected to have skeletal dysplasias. Illustrations of common Skeletal Dysplasias and Dysostoses seen in the study. Results: A total of 28 cases of skeletal dysplasia and dysostosis were identified in our study. Of these 28 cases 16 were in less than 10 years old, 10 were in the 11-20 years old age group and 2 were in the 21-30 year age group. Of these 28 cases 17 were males and 11 were females. The various types of skeletal dysplasias and dysostoses seen in our study includes Achondroplasia (7%), Chondrodysplasia Punctata(3.5%), Multiple Hereditary Osteochondromas (7%), Enchondroma (3.5%), Fibrous Dysplasias (10.7%), Proximal Focal Femoral Deficiency (3.5%), Isolated Epiphysial Dysplasia of femoral head (3.5%),Osteogenesis Imperfecta (7%), Radial Ray Anomaly (10.7%), Radioulnar Synostosis(3.5%), Brachydactyly (7%), Fibular Hemimelia (3.5%), Polydactyly Syndactyly (10.7%), Craniosynostosis, Lunotriquetral Fusion (3.5%), Dysostosis Multiplex (7%). Conclusion: Precise identification of the tye of skeletal dysplasia is paramount for proper genetic counseling. Postnatal examination and detailed radiographic examination of the fetus especially of the pelvis, limbs, skull and spine are essential to identify the type of skeletal dysplasia.Algorithmic approach of radiologist to either to diagnose a dysplasia or to help the clinician to an appropriate diagnosis. [ABSTRACT FROM AUTHOR]

Human disorders of the post-squalene cholesterol biosynthesis pathway frequently result in skeletal abnormalities, yet our understanding of the mechanisms involved is limited. In a forward-genetic approach, we have found that a late-onset skeletal mutant, named kolibernu7, is the result of a cis-acting regulatory mutation leading to loss of methylsterol monooxygenase 1 (msmo1) expression within pre-hypertrophic chondrocytes. Generated msmo1nu81 knockdown mutation resulted in lethality at larval stage. We demonstrated that this is a result of both cholesterol deprivation and sterol intermediate accumulation by creating a mutation eliminating activity of Lanosterol synthase (Lss). Our results indicate that double lssnu60;msmo1nu81 and single lssnu60 mutants survive significantly longer than msmo1nu81 homozygotes. Liver-specific restoration of either Msmo1 or Lss in corresponding mutant backgrounds suppresses larval lethality. Rescued mutants develop dramatic skeletal abnormalities, with a loss of Msmo1 activity resulting in a more-severe patterning defect of a near-complete loss of hypertrophic chondrocytes marked by col10a1a expression. Our analysis suggests that hypertrophic chondrocytes depend on endogenous cholesterol synthesis, and blocking C4 demethylation exacerbates the cholesterol deficiency phenotype. Our findings offer new insight into the genetic control of bone development and provide new zebrafish models for human disorders of the cholesterol biosynthesis pathway.

Conradi–Hunermann syndrome is a common form of chondrodysplasia punctata, inherited as X-linked dominant disorder of cholesterol metabolism due to mutation of emopamil-binding protein gene resulting in a spectrum of skeletal, cutaneous, and ocular abnormalities. One-day-old premature, cesarean-delivered female neonate admitted with xerotic, featherlike yellow-to-white hyperkeratotic scale all over the body with craniofacial defect, coarse hair, patches of cicatricial alopecia, and absent eyebrows. Baby had rhizomelic shortening of proximal limb, clinodactyly, club foot, talipes equinovarus, and bilateral congenital cataract. Radiological skeletal survey revealed punctate stippled calcification involving left femoral head epiphysis, bilateral tarsal bones, vertebral bodies of multiple thoracolumbar vertebrae, and sternum. Serum level of 8-dehydrocholesterol was elevated. Diagnosis of rare disease can be made on clinical suspicion and radiological survey in resource-limited setting.

Chondrodysplasia punctata (CDP) is a group of congenital bone and cartilage disorders. Laryngeal and tracheal calcification and subsequent stenosis are not frequently seen. We report here a case of an infant with CDP associated with tracheal stenosis.

Serratia marcescens is a global opportunistic pathogen. In vitro cytotoxicity of this bacterium is mainly related to metalloprotease serralysin (PrtS) activity. Proteolytic capability varies among the different isolates. Here, we characterized protease production and transcriptional regulators at 37°C of two S. marcescens isolates from bronchial expectorations, HU1848 and SmUNAM836. As a reference strain the insect pathogen S. marcescens Db10 was included. Zymography of supernatant cultures revealed a single (SmUNAM836) or double proteolytic zones (HU1848 and Db10). Mass spectrometry confirmed the identity of PrtS and the serralysin-like protease SlpB from supernatant samples. Elevated proteolytic activity and prtS expression were evidenced in the HU1848 strain through azocasein degradation and qRT-PCR, respectively. Evaluation of transcriptional regulators revealed higher eepR expression in HU1848, whereas cpxR and hexS transcriptional levels were similar between studied strains. Higher eepR expression in HU1848 was further confirmed through an in vivo transcriptional assay. Moreover, two putative CpxR binding motifs were identified within the eepR regulatory region. EMSA validated the interaction of CpxR with both motifs. The evaluation of eepR transcription in a cpxR deletion strain indicated that CpxR negatively regulates eepR . Sequence conservation suggests that regulation of eepR by CpxR is common along S. marcescens species. Overall, our data incorporates CpxR to the complex regulatory mechanisms governing eepR expression and associates the increased proteolytic activity of the HU1848 strain with higher eepR transcription. Based on the global impact of EepR in secondary metabolites production, our work contributes to understanding virulence factors variances across S. marcescens isolates., (© 2024 Karla L. De Anda-Mora et al., published by Sciendo.)

X-linked dominant Conradi-Hünermann syndrome (CDPX2; MIM 302960) is one of a group of disorders with aberrant punctate calcification in cartilage, or chondrodysplasia punctata (CDP). This is most prominent around the vertebral column, pelvis and long bones in CPDX2. Additionally, CDPX2 patients may have asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis and atrophoderma. The phenotype in CDPX2 females ranges from stillborn to mildly affected individuals identified in adulthood. CDPX2 is presumed lethal in males, although a few affected males have been reported. We found increased 8(9)-cholestenol and 8-dehydrocholesterol in tissue samples from seven female probands with CDPX2 (ref. 4). This pattern of accumulated cholesterol intermediates suggested a deficiency of 3beta-hydroxysteroid-delta8,delta7-isomerase (sterol-delta8-isomerase), which catalyses an intermediate step in the conversion of lanosterol to cholesterol. A candidate gene encoding a sterol-delta8-isomerase (EBP) has been identified and mapped to Xp11.22-p11.23 (refs 5,6). Using SSCP analysis and sequencing of genomic DNA, we found EBP mutations in all probands. We confirmed the functional significance of two missense alleles by expressing them in a sterol-delta8-isomerase-deficient yeast strain. Our results indicate that defects in sterol-delta8-isomerase cause CDPX2 and suggest a role for sterols in bone development.

X-linked dominant Conradi-Hünermann syndrome (CDPX2; MIM 302960) is one of a group of disorders with aberrant punctate calcification in cartilage, or chondrodysplasia punctata (CDP). This is most prominent around the vertebral column, pelvis and long bones in CPDX2. Additionally, CDPX2 patients may have asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis and atrophoderma. The phenotype in CDPX2 females ranges from stillborn to mildly affected individuals identified in adulthood. CDPX2 is presumed lethal in males, although a few affected males have been reported. We found increased 8(9)-cholestenol and 8-dehydrocholesterol in tissue samples from seven female probands with CDPX2 (ref. 4). This pattern of accumulated cholesterol intermediates suggested a deficiency of 3beta-hydroxysteroid-delta8,delta7-isomerase (sterol-delta8-isomerase), which catalyses an intermediate step in the conversion of lanosterol to cholesterol. A candidate gene encoding a sterol-delta8-isomerase (EBP) has been identified and mapped to Xp11.22-p11.23 (refs 5,6). Using SSCP analysis and sequencing of genomic DNA, we found EBP mutations in all probands. We confirmed the functional significance of two missense alleles by expressing them in a sterol-delta8-isomerase-deficient yeast strain. Our results indicate that defects in sterol-delta8-isomerase cause CDPX2 and suggest a role for sterols in bone development.

The term, "chondrodysplasia punctata" (CDP) denotes a pattern of abnormal punctate calcification of dystrophic epiphyseal cartilage and certain other cartilaginous structures, such as the larynx. CDP occurs in a variety of genetic disorders associated with skeletal dwarfism and can also be caused by prenatal exposure to warfarin. Although the most studied clinical syndrome with CDP, rhizomelic chondrodysplasia punctata (RCDP), is known to be caused by several different abnormalities of plasmalogen biosynthesis, there are many other genetic disorders with CDP for which the biochemical cause is unknown. Because patients with Smith-Lemli-Opitz syndrome, a primary disorder of sterol biosynthesis, often have rhizomesomelic limb shortness and, less commonly, CDP, we assessed sterol levels and metabolism in patients with different clinical forms of CDP. By quantitative sterol analysis of a variety of tissues, we identified 5 patients with similar radiological findings and abnormally increased levels of 8-dehydrocholesterol and cholest-8(9)-en-3beta-ol, suggesting a deficiency of 3beta-hydroxysteroid-delta8,delta7-isomerase, a principal enzyme of cholesterol biosynthesis. Cultured cells available from one patient showed increased levels of the same two sterols, decreased synthesis of cholesterol, and a pattern of inhibition by triparanol and AY-9944 consistent with a deficiency of 3beta-hydroxysteroid-delta8,delta7-isomerase. Clinical diagnoses among the 5 patients included X-linked dominant Conradi-Hünermann-Happle syndrome and nonspecific lethal CDP. We conclude that abnormal cholesterol biosynthesis is a characteristic of some clinical syndromes with rhizomesomelic dwarfing and CDP.

Objective To investigate the impact of medical and obstetric complications associated with mixed connective tissue disease (MCTD) in pregnancy. Method We analyzed 68 pregnancies from a systematic literature review and 12 pregnancies affected by MCTD at our centre between 1986 and 2015 for medical and obstetric complications. Results During pregnancy 37.1% had active MCTD and 26.7% had relapsed. Maternal complications included caesarean section (31.1%, n = 19), preeclampsia (17.6%, n = 13), thromboembolism events, and death (2.5%, n = 2 for each). Fetal complications included prematurity (48.1%, n = 25), intrauterine growth restriction (38.3%, n = 19), and neonatal lupus (28.6%, n = 18, including chondrodysplasia punctata). More than half (n = 10) of the neonatal lupus cases were explained by anti-U1RNP only. The perinatal mortality rate was 17.7% (n = 14). Pregnant women with active disease had higher rates of prematurity (OR = 7.60; 95%CI [1.93; 29.95]) and perinatal death (OR = 16.83; 95%CI [1.90; 147.70]). Conclusion MCTD in pregnancy puts women at risk of medical and obstetric complications, and disease activity probably increases this risk. [ABSTRACT FROM AUTHOR]

Background: Chondrodysplasia punctata (CDP) describes skeletal dysplasia secondary to a variety of genetic underpinnings characterized by cartilaginous stippling from abnormal calcium deposition during endochondral bone formation. Approximately 20%-38% of patients with CDP have cervical spine abnormalities, resulting in stenosis and cord compression. However, approaches to management differ among patients., Observations: The authors present an 18-year-old male with a known history of CDP and cervical kyphosis with worsening paresthesias and increased spasticity. Imaging confirmed dysplastic C4 and C5 vertebra with focal kyphosis, bony retropulsion, spinal cord compression, and myelomalacia. To treat the stenosis and deformity, the patient underwent C4 and C5 vertebrectomies with C3 to C6 anterior fusion with resolution of symptoms., Lessons: Despite many CDP patients having cervical deformities with spinal cord compression and associated neurological symptoms, there is a paucity of data on surgical management and outcomes. There are only scattered reports, and most authors recommend initial conservative management because of the high risk of operative morbidity and mortality secondary to comorbidities. When surgery is performed, long-term follow-up is recommended because of the high rates of progression of deformity, requiring subsequent operations. The authors hope that their experience adds to the literature describing the surgical management of cervical deformities in these patients.

Chondrodysplasia punctata (CDP) is a heterogeneous disease with multiple syndromic types and characterization of the CDP subtype is important for prognostic purposes. The aim of this study is to provide information about brachytelephalangic CDP, discuss its radiographic findings and emphasize the importance of cervical spine findings. Physicians must be aware of the potentially serious complications of CDP especially its cervical spine findings. In order to prevent morbidity and mortality, early imaging with CT and MRI is recommended. [ABSTRACT FROM AUTHOR]

Conradi–Hunermann syndrome is a common form of chondrodysplasia punctata, inherited as X-linked dominant disorder of cholesterol metabolism due to mutation of emopamil-binding protein gene resulting in a spectrum of skeletal, cutaneous, and ocular abnormalities. One-day-old premature, cesarean-delivered female neonate admitted with xerotic, featherlike yellow-to-white hyperkeratotic scale all over the body with craniofacial defect, coarse hair, patches of cicatricial alopecia, and absent eyebrows. Baby had rhizomelic shortening of proximal limb, clinodactyly, club foot, talipes equinovarus, and bilateral congenital cataract. Radiological skeletal survey revealed punctate stippled calcification involving left femoral head epiphysis, bilateral tarsal bones, vertebral bodies of multiple thoracolumbar vertebrae, and sternum. Serum level of 8-dehydrocholesterol was elevated. Diagnosis of rare disease can be made on clinical suspicion and radiological survey in resource-limited setting. [ABSTRACT FROM AUTHOR]

We present the radiographic images of a newborn in whom a diagnosis of chondrodysplasia punctata was reached. Patients with this disorder have pinpoint calcifications in multiple joints. [ABSTRACT FROM AUTHOR]

BACKGROUND & OBJECTIVE: Chondrodysplasia punctata (CPD) describes a diverse group of bony dysplasias, all of which share in common punctate calcification of cartilage. Symptoms include shortening of limbs, cataracts, dry and scaly skin and congenital heart diseases. In autosomal recessive form, renal and cardiac anomalies are rare. In this report, a rare case of rhizomelic chondrodysplasia punctata (RCDP) with congenital heart disease (TOF) and renal anomalies was presented.CASE: Patient is a 16-day old male infant admitted to NICU with respiratory distress and cyanosis. He was with congenital heart disease, nose bridge hypoplasia, renal anomaly, anus malposition with no cataract. The diagnosis of chondrodysplasia punctata was based on symptoms. The infant underwent mechanical ventilation and renal failure treatment but died due to neonatal sepsis.CONCLUSION: According to reported cases, in patients with RCDP evaluations for congenital heart and renal anomalies should be considered.

Chondrodysplasia punctata (CDP) is a group of skeletal dysplasias characterized primarily by punctate calcifications in cartilage. It is a rare disease with an incidence of 1:100,000 live births. Extensive airway involvement with calcification of tracheal, bronchial, and thyroid cartilage in CDP is an infrequent finding. We aim to report a case of CDP with characteristic radiological features and severe airway involvement. [ABSTRACT FROM AUTHOR]

Peroxisomes are involved in various metabolic reactions. Rhizomelic chondrodysplasia punctata (RCDP) type 1 is one of the peroxisomal biogenesis disorders caused by mutations in the PEX7 gene and is inherited in an autosomal recessive manner. We present a nine-year-old boy with skeletal abnormalities and dysmorphic facial appearance. The patient was born to parents who were first cousins. Very-long-chain fatty acids and pristanic acid levels were in the normal range, but an elevated phytanic acid level was detected by gas chromatography/mass spectrometry. The PEX7 gene was sequenced in the patient and his parents. A novel homozygous mutation, c.192delT (p.F64Lfs*10), was identified in the patient and was present in heterozygosity in both parents. In conclusion, the clinical presentation and peroxisome profile of the patient suggest that this novel mutation leads to RCDP type 1. [ABSTRACT FROM AUTHOR]

Abstract: X-linked dominant chondrodysplasia punctata (Conradi–Hünermann disease, CDPX2) is characterised by short stature, stippled epiphyses, cataracts, ichthyosiform erythroderma and patchy alopecia of the scalp. The disorder is caused by mutations within the emopamil binding protein (EBP) gene encoding a 3β-hydroxysteroid-Δ8,Δ7-isomerase. The intrafamilial variation of disease severity is a known feature of CDPX2 probably caused by skewed X-inactivation. We report on a female fetus with typical symptoms of CDPX2 such as short limbs, postaxial polydactyly, ichthyotic skin lesions and punctate calcifications. Molecular genetic analysis of the EBP gene revealed a nonsense mutation (c.328C>T, p.R110X), which was previously detected in one CDPX2 patient and in a second female patient, who was only affected on one body side and erroneously diagnosed as CHILD syndrome. Surprisingly, the mother of our fetus carries the same mutation without having any signs of CDPX2. X-inactivation studies did not reveal any evidence of skewing neither in the mother nor in the fetus. [Copyright &y& Elsevier]

Abstract: Microdeletions of Xp22.3 can result in contiguous gene syndromes, showing the variable association of apparently unrelated clinical manifestations such as ichthyosis, chondrodysplasia punctata, hypogonadotropic hypogonadism, anosmia, ocular albinism, short stature and mental retardation. We report on a boy with ichthyosis, dysmorphic features and mental retardation with ADHD. The patient was born at term after a pregnancy complicated by threatened abortion; decreased fetal movements and low estriol serum levels were reported during the last trimester. The boy was referred to us at the age of 13years. He presented with aggressive and hyperactive behavior. He had dry hair, a flat face, bilateral lens opacities, a small nose with hypoplastic tip, alae nasi and nares, a high-arched palate with a very small cleft, mixed dentition with 7 unerupted permanent teeth, left sensorineural and right mixed hearing loss with a calcified plaque of the tympanic membrane, marked shortness of terminal phalanges of hands and feet, ichthyosis of trunk and limbs. The genomic interval between AFM248th5 and KAL1 was investigated. PCR analysis showed a deletion in Xp22.3, with the distal breakpoint between the marker AFM248th5 and PABX and the proximal one between DXS278 and KAL1. Array-CGH and FISH analysis confirmed the interstitial deletion (of about 5.5Mb) and refined the breakpoints. We discuss the phenotype of our patient in relationship to the deleted segment and the possibility of mental retardation and ADHD genes in the region. [Copyright &y& Elsevier]

Kozlowski K, Basel D, Beighton P. Chondrodysplasia punctata in siblings and maternal lupus erythematosus.Chondrodysplasia punctata (CDP) was diagnosed clinically and radiographically in a male child born in Cape Town in 1991. His only sibling, a brother born in 2000 was similarly but more severely affected. The boys' mother had longstanding disseminated lupus erythematosus and epilepsy, for which she had been treated with chloraquine and other therapeutic agents during both pregnancies. The parents were non-consanguineous, and the family history was unremarkable.In addition to these affected brothers, seven previous instances of the association of CDP and maternal lupus erythematosus (MLE) have been reported. On this basis, MLE must be regarded as yet another causative factor in CDP. [ABSTRACT FROM AUTHOR]