Clinical and EEG data of 3 Italian boys (ages 3, 9, and 13 years) with severe earlyonset encephalopathy, mental retardation, facial dysmorphisms, and intractable epilepsy were found to carry missense mutations in the CDKL5 gene, in a report from Troina, Italy. Seizures were myoclonic, tonic, and partial or spasms, and the EEG abnormalities were multifocal epileptiform discharges while awake and pseudoperiodic bisynchronous dysrhythmia during sleep. Seizures were resistant to ACTH and antiepileptic drugs. Screening for these mutations is recommended in children with intractable seizures and global developmental delay. [1]

COMMENT. CDKL5 mutations are reported in girls with X-linked infantile spasms (Weaving LS et al, 2004) and in girls with atypical Rett syndrome (Evans JC et al, 2005). The association of CDKL5 mutations and seizures is rare in boys (Van Esch H et al, 2007). The recognition of this genetic diagnosis would be helpful in counseling concerning outcome.

The role of genetics in diagnosis and treatment of epilepsy was discussed at the First North American Regional Epilepsy Congress; 60th Annual Meeting of the American Epilepsy Society, Dec 1-5, 2006, San Diego, CA [2]. The nocturnal frontal lobe epilepsy gene, autosomal dominant with 75% penetrance, was one of the first identified. The gene mapped to chromosome 20q and the nicotinic receptor opened the door to the channelopathies. Voltage-gated ion channel subunits are involved in GEFS+, Dravet’s syndrome, and infantile seizures; potassium channels in neonatal seizures; and potassium and calcium channels in absence epilepsy. SCN1A gene controls the sodium channel subunit in Dravet’s syndrome, febrile seizures, febrile seizures plus, and myoclonic-astatic epilepsy. SCN1A mutations occur in 79% of severe myoclonic epilepsies of infancy (SMEI) and 69% of borderline cases [3, 2].