A CASE SERIES OF PHYLLOID HYPOMELANOSIS

THE PHYLLOID HYPOMELANOSIS is a defined as a distinct syndrome consisting of achromic phylloid skin lesions in combination with extracutaneous anomalies such as mental retardation , agenesis of corpus callosum , conductive hearing loss ,coloboma and various skeletal defects[1].

Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity

Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation (“handshake”), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.

Neurodevelopmental Outcome of Patients With Agenesis of Corpus Callosum

Background: Agenesis of Corpus Callosum (ACC) is a type of brain dysgenesis with various clinical manifestations. Objectives: This study aimed to investigate the clinical and neurodevelopmental outcomes of patients with ACC. Materials & Methods: In this cross-sectional study, the clinical and neurodevelopmental conditions of 62 patients with complete ACC referred to subspecialty clinics of pediatric neurology, Isfahan University of Medical Sciences, Isfahan, Iran, were investigated. Quantitative data were shown as Mean±SD, and qualitative data as frequency or percentage. In addition, the f Chi-square test was used to compare some data in SPSS version 22. Results: In this study, 62 patients, including 29 boys and 33 girls with a Mean±SD age of 4.99±5.07 years, were included. Among the patients examined, 54.4% were born of consanguineous marriage, 82% had developmental delays, 80.4% had mental retardation, 89.1% had a speech delay, 23.7% had nutritional problems, 42.4% had facial dysmorphic features, and 27.6% had abnormalities of muscle tone. Among the associated problems stated by the patients, 15.5% of them had heart diseases, 22.4% visual disorders, 5.2% hearing deficit, 25.8% behavioral problems, 50% seizures, and 53.3% had abnormal electroencephalogram. Interestingly, 12.9% of the patients had normal or near-normal development. Conclusion: The prevalence of developmental delays, speech and language disorders, mental retardation, facial deformities, seizures, and abnormal muscle tone were common in the patients with ACC.

Neurodevelopmental Outcomes following Prenatal Diagnosis of Isolated Corpus Callosum Agenesis: A Systematic Review

Abnormalities of corpus callosum are one of the most common brain anomalies. Fetuses with isolated corpus callosum agenesis (CCA) have a better prognosis than those with additional anomalies. However, unpredictable neurodevelopmental outcomes of truly isolated CCA make prenatal counseling a challenge. The aim of this review is to evaluate neurodevelopmental outcomes in children with prenatal diagnosis of isolated CCA. Controlled clinical trials published between May 23, 2009, and May 23, 2019, using the MeSH term “agenesis of corpus callosum” were reviewed. A total of 942 articles were identified, and 8 studies were included in the systematic review depending on the inclusion criteria. These studies included 217 fetuses with isolated CCA and no other anomalies at prenatal assessment. Neurodevelopmental outcome was reported to be normal in 83 children with a prenatal diagnosis of isolated CCA confirmed at birth within 128 completed assessments. About 45 children presented borderline, moderate, or severe neurodevelopmental outcome. In this review, neurodevelopment was favorable in two-thirds of the cases, but mild disabilities emerged in older children. Despite this, disabilities can occur later beyond school age and a low risk of severe cognitive impairment exists. Our study highlights the essential early diagnosis and proper supportive therapy.

A Case Report of a Prenatally Missed Mowat-Wilson Syndrome With Isolated Corpus Callosum Agenesis

Mowat–Wilson syndrome (MWS) is an autosomal dominant genetic disorder caused by ZEB2 gene mutations, manifesting with unique facial characteristics, moderate to severe intellectual problems, and congenital malformations as Hirschsprung disease, genital and ophthalmological anomalies, and congenital cardiac anomalies. Herein, a case of 1-year-old boy with isolated agenesis of corpus callosum (IACC) in the prenatal period is presented. He was admitted postnatally with Hirschsprung disease (HSCR), hypertelorism, uplifted earlobes, deeply set eyes, frontal bossing, oval-shaped nasal tip, ‘‘M’’ shaped upper lip, opened mouth and prominent chin, and developmental delay. Hence, MWS was primarily considered and confirmed by the ZEB2 gene mutation analysis. His karyotype was normal. He had a history of having a prenatally terminated brother with similar features. Antenatally detected IACC should prompt a detailed investigation including karyotype and microarray; even if they are normal then whole exome sequencing (WES) should be done.