Familial Lennox‐Gastaut syndrome in male siblings with a novel DCX mutation and anterior pachygyria

• Published in: Epilepsia (Copenhagen) Vol. 51; no. 9; pp. 1902 - 1905
• Main Authors: Lawrence, Kate M., Mei, Davide, Newton, Mark R., Leventer, Richard J., Guerrini, Renzo, Berkovic, Samuel F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2010; Wiley-Blackwell
• Subjects: Age; Biological and medical sciences; Brain malformation; Complex syndromes; Diseases in Twins - genetics; DNA Mutational Analysis; DNA sequencing; Doublecortin; Doublecortin protein; EEG; Electroencephalography; Epilepsies, Myoclonic - diagnosis; Epilepsies, Myoclonic - genetics; Epilepsy; Epilepsy - diagnosis; Epilepsy - genetics; Epilepsy, Generalized - diagnosis; Family; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Lennox‐Gastaut syndrome; Lissencephaly - diagnosis; Lissencephaly - genetics; Male; Medical genetics; Medical sciences; Mental retardation; Microtubule-Associated Proteins - genetics; Middle Aged; Missense mutation; Mutation, Missense - genetics; N.M.R; Nervous system (semeiology, syndromes); Neuroimaging; Neurology; Neuropeptides - genetics; Pachygyria; Pedigree; Phosphoproteins - genetics; Receptors, G-Protein-Coupled - genetics; Seizures; Siblings; Syndrome; X chromosome; Lennox syndrome; Brain malformation; Nervous system diseases; Lennox-Gastaut syndrome; Doublecortin; Epilepsy; Central nervous system disease; Pachygyria; Sibling; Mutation; Congenital disease; Cerebral disorder
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2010.02694.x

Summary 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.