Molecular Genetics Rett Syndrome, Atypical, CDKL5, Sequencing

Aytpical Rett syndrome (also known as Epileptic Encephalopathy, Early Infantile, 2 (EIEE2);  Infantile Spasm Syndrome, X-Linked (ISSX2); and Rett Syndrome, Variant, with Infantile Spasms) is an X-linked, severe progressive neurodevelopmental disorder that generally presents in infancy with early onset seizures during the first weeks to months of life.  Infantile spasms and myoclonic jerks are the cardinal feature of this disorder, (with a unique EEG pattern) most frequently marked by hypotonia, poor eye contact, severe mental retardation and profound global developmental delay.  Usually there is no period of regression which is often seen in Rett syndrome, the hand movements are less notable but grasp is affected.   In the majority, growth is normal except head circumference is variably affected and autonomic disturbances are not noted. This presentation is far more frequent in females than in males although males can be affected. Variable clinical   presentation may occur with milder psychosocial phenotypes resembling autistic features and tactile hypersensitivities.  Atypical Rett syndrome presenting with early onset seizures may be associated with mutations and this would be a clear indication to consider CDKL5 testing.  Approximately 10% of patients with encephalopathy and early onset seizures carry an identified mutation in the CDKL5 gene, cyclin dependent kinase-like 5 gene (CDKL5) on chromosome Xp22.1.  

Reasons for Referral:

• Confirmation of clinical diagnosis in patients with atypical Rett, or suspicion based on infantile spasms AND with a negative MECP2 mutation screen.
• Carrier testing of family members of Atypical Rett patients, given previous CDKL5 mutation identified.
• Prenatal diagnosis, given previous CDKL5 mutation identified.

For detailed information and ordering instructions, please refer to Full Gene Analysis (1240). Genes may be added or removed from the list below if clinically indicated.