Abstracts

Mutations in the cyclin-dependent kinase-like 5 gene ([italic]CDKL5[/italic]) have been detected in girls with the atypical Rett syndrome variant (MIM 312750) that is characterized by early-onset infantile spasms and severe neurodevelopmental retardation. We present a young boy with early-onset infantile spasms, severe encephalopathy, tetralogy of Fallot, and bilateral cataract, in whom a deletion at Xp22 comprising the Nance Horan Syndrome ([italic]NHS[/italic]) gene and [italic]CDKL5[/italic] gene was detected by array-CGH., Brain MRI, video EEG, metabolic and infectious work-up, karyotype, subtelomeric screening, and array-CGH were carried out in the proband., The boy was diagnosed shortly after birth with a Tetralogy of Fallot, mild facial dysmorphism, extreme hypotonia, and bilateral microphthalmia with microcornea and congenital nucleocortical cataract. At age 7 weeks he developed myoclonic seizures, occurring most frequently post-prandial or during drowsiness. EEGs during wakefulness and sleep were normal. At age 4 months, the seizure pattern was consistent with infantile spasms, but no hypsarrhythmia was seen on EEG. At age 5 months, he developed tonic spasms, sometimes preceded by crying or accompanied by laughter or oral automatisms. A video EEG at age 6 months showed multiple myoclonic jerks without EEG correlate, as well as several tonic spasms characterized by sudden onset low voltage rhythmic diffuse 15 Hz activity followed by generalized slowing. No typical epileptiform activity was seen. Seizures were resistant to treatment with valproic acid, vigabatrine, topiramate, phenobarbital and levetiracetam. At age 10 months, he is severely retarded with no reaction to light stimuli, severe axial hypotonia, and absent midline organization. Additional investigations were normal, except for a [italic]de novo[/italic] deletion of approximately 2.8 Mb at Xp22 including 16 genes of which the only known disease-associated genes are the [italic]NHS[/italic] gene that causes the ophthalmologic abnormalities and the [italic]CDKL5[/italic] gene that is responsible for the severe epileptic encephalopathy., This is the first description of a male patient with a deletion of the [italic]NHS[/italic] and [italic]CDKL5[/italic] genes, showing the involvement of [italic]CDKL5[/italic] in severe epileptic encephalopathy in males. The epilepsy phenotype was characterized by drug-resistant early-onset infantile spasms, tonic spasms and myoclonic jerks, without clear epileptiform EEG correlate., (Supported by: H.V.E. is a post-doctoral researcher of the FWO-Vlaanderen. M.B. is a doctoral student of the IWT-Vlaanderen. This work was supported by a research grant G-0229-01 of the FWO-Vlaanderen, Belgium.)