Two Siblings With a CDKL5 Mutation: Genotype and Phenotype Evaluation

Eveline E. O. Hagebeuk, Carlo L. Marcelis, Mariëlle Alders, Ageeth Kaspers, Al W. de Weerd

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This is the second report of a family with a recurrence of a CDKL5 mutation (c. 283-3_290del) in 2 sisters. Both parents tested negative for the mutation in all tissues, but germline mosaicism is likely. Clinically CDKL5 patients resemble those with Rett syndrome, caused by a MECP2 mutation, who experience a regression, after an initial normal development. Even though both siblings showed a typical CDKL5 phenotype, their presentation is different. From birth, the oldest daughter had a severe developmental delay, feeding problems, and hypotonia and experienced daily refractory seizures. The youngest daughter appeared to be normal until age 3 months. At that age seizures started, deterioration and regression became evident, and an epileptic encephalopathy developed. This report of familial recurrence, with suspected germline mosaicism in a healthy parent, has important consequences for genetic counseling. Although it is not possible to predict an exact recurrence risk, it is likely to be increased
Original languageEnglish
Pages (from-to)1515-1519
JournalJournal of Child Neurology
Issue number11
Publication statusPublished - 2015

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