Brain malformation, neurodevelopmental disorder and epilepsy in a case of two rare genetic diseases: overlapping...

In most cases there is a single etiological factor causing neuromotor developmental delay and epilepsy while sometimes more than one gene may be involved. These include the autosomal recessive inherited CAMSAP1 gene, which is associated with cortical developmental malformations such as pachygyria and lissencephaly and the autosomal dominant inherited NBEA gene, which plays crucial roles in vesicle trafficking as well as synapse structure and function. Loss of function of both genes together is a well-known disease mechanism. We report a 7-year-old girl with early-onset epilepsy, severe neuromotor developmental delay and brain malformation. Whole exome analysis of the patient revealed c.1153C > T p.Gln385* nonsense homozygous likely pathogenic variant in CAMSAP1 gene and c.6867G > A p.Trp2289* nonsense heterozygous pathogenic de novo variant in NBEA gene. A small number of cases associated with these genes have been reported. We report the 8th case reported in the CAMSAP1 gene and the overlapping phenotype in these two genes.