Agenesis of the corpus callosum: What to tell expecting parents?

Abstract

Agenesis of the corpus callosum (ACC) is one of the most common brain malformations, with an incidence estimated to range from 0.5 to 70 in 10,000 among the general population. Prenatal diagnosis is made via ultrasound; however, fetal MRI is useful to confirm or exclude the presence of associated cerebral abnormalities–mostly cortical malformations–that may affect postnatal prognosis. When no additional central nervous system (CNS) or extra CNS anomalies are identified and no genetic cause is found, an isolated ACC is diagnosed. Overall, in cases of ACC, an underlying genetic cause can be identified in up to 12.5% with chromosomal microarray (CMA) and up to 47% with whole exome sequencing (WES). In cases where ACC is the only anomaly detected, the yield of WES is 30%. Postnatal outcomes are variable and depend on whether the condition is isolated or not. In truly isolated ACC, outcomes range from normal in 65% of cases through mild to severe neurodevelopmental impairments in 35% of cases. An interdisciplinary team of medical experts is key in guiding parents toward informed decision‐making in pregnancies complicated by ACC. Considering current and expected advancements in genetic testing and imaging technologies in upcoming years, we herein summarize current recommendations for the management and prenatal counseling of expecting parents of fetuses with ACC. Our review pertains primarily to expecting parents of fetuses with complete ACC.

Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly

“…However, higher expression was observed in the postmitotic neurons as early as E16.5 majorly in forebrain and midbrain, which supports potential role in cell migration and axonal guidance for the neurons to reach their functioning regions and connectivity points. These processes when interrupted cause morphogenesis related disorders such as agenesis of corpus callosum, microgyria, and agyria which ultimately lead to ID, microcephaly, developmental delays, poor muscle tone, and motor function 18 – 21 . We observed similar deficits in our cohort (Table 1 ).…”