A maternally inherited frameshift CDKL5 variant in a male with global developmental delay and late‐onset generalized epilepsy

Pathogenic CDKL5 variants cause an X‐linked dominant infantile epileptic encephalopathy, predominantly in females. This condition is characterized by an early‐onset severe mixed seizure disorder. We present a maternally inherited frameshift CDKL5 c.2809_2810insA p.(Cys937Ter) variant in a 13‐year‐old male with severe intellectual disability and late‐onset generalized epilepsy. Interestingly, the variant segregation in the family is consistent with an X‐linked recessive inheritance pattern, which has not previously been described with this gene. This variant is expected to result in truncation of some CDKL5 transcripts, which could potentially account for the later seizure onset and atypical inheritance pattern. Though the possibility of this variant not being causal cannot be completely excluded, this case adds to the variability of the documented phenotypic profile and to the debate around the role of C‐terminus variants in CDKL5‐related disease.

from Genetics via xlomafota13 on Inoreader http://bit.ly/2LYSfI7
via IFTTT