Familial Lennox-Gastaut syndrome in male siblings with a novel DCX mutation and anterior pachygyria.
Lennox-Gastaut syndrome (LGS) has numerous causes,but only rarely has familial recurrence been observed. We studied a family in which three male members had severe epilepsy and intellectual disability. The proband had seizure onset at 7 years of age with atonic, myoclonic, atypical absence, and tonic seizures with slow spike-wave on electroencephalography (EEG). One living sibling had a similar clinical pattern. One deceased sibling was known to have had seizures with intellectual disability. Neuroimaging revealed anterior predominant pachygyria. DNA sequencing of the gene doublecortin (DCX) on the X chromosome revealed a novel missense mutation in the two living affected male siblings. The occurrence of three affected male family members with proven or suspected LGS in this family was puzzling and only solved by a combination of magnetic resonance (MR) and molecular genetics evaluations. This finding provided essential information for genetic counseling.
Lawrence
Kate M
KM
Epilepsy Research Centre, Austin Health and University of Melbourne, Melbourne, Australia.
Mei
Davide
D
Newton
Mark R
MR
Leventer
Richard J
RJ
Guerrini
Renzo
R
Berkovic
Samuel F
SF
D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000175:diagnosis; D005190:Family; D005260:Female; D006801:Humans; D054082:Lissencephaly / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D035781:Siblings; D013577:Syndrome
C118925:ADGRG1 protein, human; C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled