MICrocephaly, disproportionate pontine and cerebellar hypoplasia syndrome: A clinico-radiologic phenotype linked to calcium/calmodulin-dependent serine protein kinase gene mutation
A 2-year-old Asian girl was referred to pediatric neurology service with global developmental delay and growth restriction. She could sit unaided and roll over, but was unable to stand without support. She could not speak clear meaningful words.\nShe was born at term by normal vaginal delivery to un-related healthy parents. Pregnancy was unremarkable for infection, exposure to known teratogens, polyhydramnios or decreased fetal movements. She did not require resuscitation at birth or admission to neonatal unit. Her head circumference at birth was below 0.4th centile. She was both breast and bottle fed. During the weaning period, she struggled with lumpy food and failed to gain weight beyond 6 months. Consequently, she was started on nasogastric tube feeding. Family history was unremarkable for developmental delay or microcephaly.\nClinical assessment revealed microcephaly, low weight (<0.4th centile), an open mouthed appearance with thickened alveolar ridges, prominent maxilla, bilateral epicanthic folds, short nose, long philtrum, large ears, hypoplastic 5th toe nails, delayed neurodevelopmental milestones, low axial tone, and slightly increased peripheral tone, more so in the lower limbs. Her audiological and ophthalmological assessments were unremarkable. Physiotherapy and Speech and Language Therapy, and dietetic inputs were in place.\nAs a part of her diagnostic work-up, she underwent extensive investigations. Magnetic resonance imaging (MRI) showed prominent lateral ventricles, mega cisterna magna, small cerebellum, and normal corpus callosum []. Neurometabolic investigations were normal and Toxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex (TORCH) studies were negative.\nShe was referred to clinical genetics team with a view to assigning a syndromic diagnosis. Conventional cytogenetic studies were reported normal. Subsequently, an a-CGH analysis was carried out, which revealed CASK gene duplication at Xp11.4.