Severe intellectual disability, absence of language, epilepsy, microcephaly and progressive cerebellar atrophy related to the recurrent de novo variant p.(P139L) of the CAMK2B gene: A case report and brief review

The CAMK2B gene encodes the β-subunit of calcium/calmodulin-dependent protein kinase II (CAMK2), an enzyme that has crucial roles in synaptic plasticity, especially in hippocampal and cerebellar neurons. Heterozygous variants in CAMK2B cause a rare neurodevelopmental disorder, with 40% of the reported cases sharing the same variant: c.416C>T, p.(P139L). This case report describes a 22-year-old patient with this recurrent variant, who presents with severe intellectual disability, absence of language, hypotonia, microcephaly, dysmorphic features, epilepsy, behavioral abnormalities, motor stereotypies, optic atrophy, and progressive cerebellar atrophy. Notably, this patient is the oldest reported so far and allows us to better delineate the clinical phenotype associated with this variant, adding clinical aspects never described before, such as epilepsy, optic atrophy, scoliosis, and neuroradiological changes characterized by progressive cerebellar atrophy.