CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature.
Cyclin-dependent kinase-like 5 (CDKL5) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases ofCDKL5gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 ofCDKL5.All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact,CDKL5gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future.
Department of Neurology and Neurorehabilitation, Children's Clinic, Tartu University Hospital, Tartu, Estonia.
Stella
S
Lilles
Department of Neurology and Neurorehabilitation, Children's Clinic, Tartu University Hospital, Tartu, Estonia.
Inga
I
Talvik
Department of Neurology and Neurorehabilitation, Children's Clinic, Tartu University Hospital, Tartu, Estonia.
Klari
K
Noormets
Department of Neurology and Neurorehabilitation, Children's Clinic, Tartu University Hospital, Tartu, Estonia.
Ulvi
U
Vaher
Department of Pediatrics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
Katrin
K
Õunap
Department of Pediatrics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
Tiia
T
Reimand
Department of Neurology and Rehabilitation, Tallinn Children's Hospital, Tallinn, Estonia.
Valentin
V
Sander
Department of Radiology, Radiology Clinic, Tartu University Hospital, Tartu, Estonia.
Pilvi
P
Ilves
Department of Neurology and Neurorehabilitation, Children's Clinic, Tartu University Hospital, Tartu, Estonia.
Tiina
T
Talvik
D000293:Adolescent; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics*; D004957:Estonia; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013036:Spasms, Infantile / Q000235:genetics*
D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human