Early onset seizures and Rett-like features associated with mutations in CDKL5.
Mutations in the CDKL5 gene (also known as STK9) have recently been shown to cause early onset epilepsy and severe mental retardation (ISSX or West syndrome). Patients with CDKL5 mutations sometimes also show features similar to those seen in Rett Syndrome (RTT). We have screened the CDKL5 gene in 94 patients with RTT or a RTT-like phenotype who had tested negative for MECP2 mutations (13 classical RTT female subjects, 25 atypical RTT female subjects, 40 RTT-like female and 16 RTT-like male subjects; 33 of the patients had early onset seizures). Novel pathogenic CDKL5 mutations were identified in three girls, two of whom had initially been diagnosed with the early onset seizure variant of RTT and the other with early onset seizures and some features of RTT. In addition, the 33 patients with early seizures were screened for the most common mutations in the ARX gene but none were found. Combining our three new cases with the previously published cases, 13/14 patients with CDKL5 mutations presented with seizures before the age of 3 months.
Evans
Julie C
JC
Department of Medical Genetics, Cardiff University, Heath Park, Cardiff, UK. evansjc6@cardiff.ac.uk
Archer
Hayley L
HL
Colley
James P
JP
Ravn
Kirstine
K
Nielsen
Jytte Bieber
JB
Kerr
Alison
A
Williams
Elizabeth
E
Christodoulou
John
J
Gécz
Jozef
J
Jardine
Philip E
PE
Wright
Michael J
MJ
Pilz
Daniela T
DT
Lazarou
Lazarus
L
Cooper
David N
DN
Sampson
Julian R
JR
Butler
Rachel
R
Whatley
Sharon D
SD
Clarke
Angus J
AJ
D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
C469264:ARX protein, human; D018398:Homeodomain Proteins; D022821:RNA Splice Sites; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human