CDKL5 deficiency
CDKL5 deficiency is characterized by early-onset seizures, often presenting as infantile spasms and usually occurring within the first 3 months of life, global developmental delay, severely impaired gross motor function and cortical visual impairment. CDKL5 deficiency is caused by dominantly acting loss-of-function variants in the X-linked gene CDKL5 (cyclin-dependent kinase-like 5), which plays a crucial role in brain development. The incidence of CDKL5 deficiency is estimated at 1 in 40.000 to 60.000. The diagnosis of CDKL5 deficiency is increasing due to the growing awareness of the disorder and the inclusion of CDKL5 in routine genetic testing of early-onset epileptic encephalopathies. CDKL5 is often caused by de novo variants. Female patients with a clinical diagnosis of Rett syndrome, severe infantile seizures, or atypical Rett syndrome, may have a CDKL5 mutation.
