New VOUS in CASK Gene Correlating with the MICPCH Phenotype.

We present the case of a three-year-old girl with normal family history who was admitted to our hospital for medical recovery. The patient had microcephaly, pontocerebellar hypoplasia, slight facial dysmorphism, axial hypotonia, epileptic seizures, absent walking skills and severe speech delay. Genetic testing identified a heterozygous intronic variant in the CASK gene, namely CASK c.278 + 5G>A, which has never been reported in the medical literature or in other databases (gnomAD, ClinVar, HGMD). In mammals as well as more distant species, the G nucleotide is fully conserved at this position, suggesting it may not tolerate variation. In silico tools predict the substitution to be deleterious. Pathogenic mutations of these gene are responsible of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome, which overlaps completely with our patient's phenotype.