To describe a rare etiology of microcephaly and pontocerebellar hypoplasia (PCH) in a male patient.

PCH is a diverse group of disorders, phenotypically characterized by neurodevelopmental delay with or without early degeneration of the cerebellum and brainstem. Genotypic classification of PCH has been insightful in subtyping its different forms. Of these, loss of function variants in the CASK (calcium/calmodulin-dependent serine protein) kinase have been associated with microcephaly with pontine and cerebellar hypoplasia (MICPCH) and X-linked intellectual disability. While there have been several cases of females with MICPCH reported; only a few affected males have been described. 

Case report and review of literature.

A 3-day-old term infant with a prenatal diagnosis of intra-uterine growth retardation and “extremely small cerebellum and mega cisterna magna” presented to our facility for further evaluation. Family history was pertinent for a 14-month-old sister with developmental delay. He had poor respiratory effort at birth and required assistive ventilation for the same. Initial physical exam was pertinent for large posterior rotated ears, microcephaly with prominent occiput, abnormal posture of upper extremities and lack of response to needle sticks. The patient was below the third percentile for weight, height and head circumference for his age. MRI Brain confirmed pontocerebellar hypoplasia. Chromosomal microarray analysis was relevant for loss on Xp11.4, an inactivating mutation involving exon 5 of CASK gene. He also had a loss at 2q11.2 including part of VWA3B indicating he was likely a carrier for autosomal recessive spinocerebellar ataxia 22. 

His post-natal course was complicated by laryngomalacia, chronic respiratory failure, obstructive sleep apnea, seizures, global developmental delay and failure to thrive requiring recurrent hospitalizations. At 10 months of age, the patient passed away after a cardio-respiratory arrest. 

CASK-related MICPCH is a rare etiology of PCH presenting with a much more severe phenotype in males compared to females.