Clin Neurophysiol. 2005 Nov 30; [Epub ahead of print]
Myoclonic encephalopathy in the CDKL5 gene mutation
Buoni S, Zannolli R, Colamaria V, Macucci F, di Bartolo RM, Corbini L, Orsi A, Zappella M, Hayek J.
Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Pediatrics, University of Siena, Siena, Italy.
Abstract
OBJECTIVE: Epilepsy with mutation of the CDKL5 gene causes early seizures and is a variant of Rett syndrome (MIM (312750), which is reported typically as infantile spasms. The purpose of this study was to analyze the epileptic histories and EEGs of patients with the CDKL5 mutation. METHODS: We reviewed the epilepsy histories and electroclinical analyses of three girls aged 9.5, 7.4, and 9.4 years, each with a mutation of the CDKL5 gene. RESULTS: We revealed the presence of an encephalopathy that started by 1.5 months of age. At first, seizures involved tonic spasms or complex partial seizures, and were complicated by the later appearance of complex partial, tonic, and unexpectedly, myoclonic seizures. This form of epilepsy was drug resistant. Routine and prolonged video EEGs both displayed a homogeneous electroclinical pattern consisting of (a) unique background with diffuse high voltage sharp waves of 6-7Hz, and absence of the typical rhythmic frontal-central theta activity present in Rett syndrome; (b) unique awake and sleep background, with diffuse, high voltage, continuous sharp waves with multifocal and diffuse spikes; (c) rhythmic, diffuse, 15Hz activity accompanied clinically by tonic seizures; (d) intercritical pattern with pseudoperiodic, diffuse, sharp waves or pseudoperiodic, diffuse spike and polyspike or wave discharges; and (e) diffuse, spike, polyspike and wave discharges accompanied by massive or focal myoclonias or both. CONCLUSIONS: Patients with the CDKL5 mutation have an early onset, epileptic encephalopathy in infancy that evolves into myoclonic seizures in childhood with a unique EEG pattern. SIGNIFICANCE: Recognizing this type of encephalopathy could be useful in prompting clinicians to proceed further with their diagnostic work in patients not fitting the criteria of classical Rett syndrome.
Lay Summary
Mutations in CDKL5 are often accompanied with epilepsy, and are considered an atypical form of Rett Syndrome. In this case report, the authors retrospectively document the epileptic histories and the analyses of the electrical activity of the brain activity (EEGs, or electroencephalograms) of three girls (aged 9.5, 7.4, and 9.4 years), each with a CDKL5 mutation. It was realized that all three girls had a measurable brain disorder by 1.5 months of age, which ultimately developed into drug-resistant seizures. The authors go on to describe the unique clinical features of the measured brain activity, as a tool for future clinical diagnoses. Indeed, this paper encourages the early recognition of this type of alteration in brain activity pattern by clinicians, thus clearly aiding in the diagnoses of girls with atypical Rett Syndrome