title: Two Siblings With a CDKL5 Mutation: Genotype and Phenotype Evaluation.
abstract: 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.
authors.affiliation: Department of Pediatric Neurology, Stichting Epilepsie Instellingen Nederland, Zwolle, Netherlands ehagebeuk@sein.nl.
authors.forename: Eveline E O
authors.initials: EE
authors.lastname: Hagebeuk
authors.affiliation: Department of Genetics, Radboud University Medical Centre, Nijmegen, Netherlands.
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Marcelis
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Mariëlle
authors.initials: M
authors.lastname: Alders
authors.affiliation: Department of Pediatrics, Medical Spectrum Twente, Enschede, Netherlands.
authors.forename: Ageeth
authors.initials: A
authors.lastname: Kaspers
authors.affiliation: Sleepcenter of Stichting Epilepsie Instellingen Nederland (SEIN), Zwolle, Netherlands.
authors.forename: Al W
authors.initials: AW
authors.lastname: de Weerd
mesh_terms: D001921:Brain / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012640:Seizures / Q000235:genetics / Q000503:physiopathology; D035781:Siblings
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human
keywords: CDKL5 disorder; clinical presentation; electroencephalography; familial presentation; genetic counseling; germline mosaicism; phenotype