Neuropediatrics 2013; 44 - VS13_02
DOI: 10.1055/s-0033-1337702

A new heterozygote sequence variant of the CDKL5 Gene as the underlying cause of intractable early infantile epilepsy

S Heimering 1, A Abicht 2, A Fiedler 3
  • 1Klinik für Kinder und Jugendliche, Klinikum St. Marien, Amberg, Germany
  • 2Medizinisch-Genetisches Zentrum, München, Germany
  • 3Klinik für Kinder und Jugendliche, Amberg, Germany

We describe the case of a 5-month-old girl of nonconsanguineous parents.

At the age of 9 weeks, focal rapid generalizing epileptic seizures were realized. The seizures started with cloni of the left arm with fast generalization into tonic clonic episodes. In the ictal electroencephalogram (EEG), tonic pattern were found. The interictal EEG showed sharp waves of the frontal-precentral region were found.

The clinical course showed delay of motor and mental development with progressing muscular hypotonia after seizure manifestation. Magnetic resonance imaging (MRI) of the brain as well as neurometabolic work up were uneventful.

DNA sequencing showed a so far not described sequence variant in the CDKL5 gene. c.145G > A; p.Glu49Lys in a heterozygote pattern. This variant leads to loss of the Exon 4 on RNA level. Segregation analysis of the parents did not show this mutation.

Under combination therapy with carbamazepine, levetiracetam, and topiramate, the seizures are moderately controlled. The motor and mental development is still moderately disturbed but continuously progressing.

Conclusion: Our case underlines the relatively high incidence of associated CDKL5 mutations in girls with therapy refractory early infantile epilepsies.