Presence of the clinical features described above.
Rett Syndrome with infantile epilepsy - CDKL5
Clinical Features
Children with mutation in the CDKL5 gene suffer infantile epilepsy within the first 3 months of life. In addition to epilepsy, these children also have muscle hypotonia and little eye contact. In this early stage, inter-ictal EEG can be normal.
The development of epilepsy in children with a CDKL5 gene mutation manifests itself in the following stages:
- Stage I: early epilepsy
Tonic-clonic seizures; often brief episodes lasting less than a minute; on average 2 to 5 times per day, often with normal EEG readings
- Stage II: epileptic encephalopathy
Tonic seizures along with infantile spasms. EEG readings are pathologic. The children are severely retarded, have severe hypotonia, and show no signs of linguistic or visual interaction. Advances in development are also absent. Drug therapy can improve the spasms and/or seizures in some patients and can also help with the developmental delay.
- Stage III: late multifocal and myoclonic epilepsy
At this stage, two groups of patients can be differentiated: those cases in which drug therapy reduces the frequency of the seizures and improves EEG results, and those more unfortunate cases displaying resistance to therapy and multifocal and myoclonic epilepsy.
In the early literature, children with mutation in the CDKL5 gene were classified with the clinical features of Rett Syndrome. Now we know that the pattern of epilepsy is different from that of Rett patients. Of the latter, only 50 to 80% of cases are accompanied by epilepsy, most often beginning in the pseudostationary stage (between ages 3 and 10). Motor problems such as tremor, twitching, laughing or hyperventilating are not observed in children with CDKL5 mutations.
Only children with the Hanefeld variant of Rett Syndrome suffer epilepsy similar to that of CDKL5.
Genetic Information
The CDKL5 gene is located on the short arm of the X chromosome (Xp22) and consists of 20 coding and 3 non-coding exons. Functionally, it possibly participates in regulating the MECP2 gene. In most of the cases described in the literature, affected patients are girls. It is thus safe to assume an X chromosomal pattern of inheritance.
Diagnostic
Indication
Method
All exons as well as their flanking regions are analysed using DNA sequencing. Deletions and duplications of one or more exons are detected using MLPA.
Sample Requirement
2 - 4 ml of EDTA blood
Duration
3 - 4 weeks