Teaching Video NeuroImage: <i>CASK</i> -Related Pontocerebellar Hypoplasia With Complex Movement Disorder

A 16-year-old adolescent girl with intellectual disability and atypical Rett-like features (language delay, midline hand stereotypies, and microcephaly) developed psychomotor regression and seizures (bilateral tonic-clonic seizures and head drops) at age 10.Initial examination revealed dysmorphism (broad forehead/nose, hypertelorism, and exotropia), spastic quadriparesis, and chorea involving predominantly the face and left upper and lower limbs, with superimposed dystonia (Video 1-segment A).An intercurrent febrile illness at age 15 precipitated worsening of movements, with focal myoclonus in the left hand and jaw-opening and truncal dystonia (no EEG correlate) (Video 1-segments B and C).MRI brain showed moderate asymmetric cerebellar hypoplasia with mild pontine hypoplasia (Figure).Whole-exome sequencing identified a likely pathogenic heterozygous (X-linked dominant) missense variant (c.1322T>C, p.Leu441Pro) in exon 15 of the calcium/calmodulin-dependent serine protein kinase (CASK) gene.Although CASK-related disorders typically cause diverse phenotypes including pontocerebellar hypoplasia, neurodevelopmental disorders, and epileptic encephalopathy, our case highlights the presentation of a complex movement disorder, expanding the clinical spectrum. 1,2