Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common.
MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.
MECP2 mutations in females lead to Rett syndrome, a neurological disorder characterized by developmental stagnation and regression, loss of purposeful hand movements and speech, stereotypic hand movements, deceleration of brain growth, autonomic dysfunction and seizures.
Although the phenotype of CDKL5 mutation is similar to Rett syndrome caused by MECP2 mutation, the former is characterized by early-onset seizures and association with West syndrome.
Because most cases of RTT are caused by mutations in the MECP2 gene it is reasonable to assume that convulsions are based on common pathogenetic mechanisms and thus should have a similar response to antiepileptic drugs.
In this study we screened several cohorts of children for CDKL5 mutations, totaling 316 patients, including individuals with a clinical diagnosis of RTT but who were negative forMECP2 mutations (n=102), males with X-linked mental retardation (n=9), patients with West syndrome (n=52), patients with autism (n=59), patients with epileptic encephalopathy (n=33), patients with Aicardi syndrome (n=7) and other patients with intellectual disability with or without seizures (n=54).
Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome.
Mutations of the MECP2 gene should be considered early in males with hypotonia, developmental delay, profound intellectual impairment, and seizures, associated with a mother with psychosocial, cognitive, and gastrointestinal impairments.
The clinical sensitivity of CDKL5 mutation screening among females with Rett-like features and negative MECP2 screening was 7.8% while the clinical sensitivity among females having cryptogenic intractable seizures with an onset before the ages of 12, 6 and 3 months were 4.7, 11.6 and 14.3%, respectively.