Paternal germline mosaicism of a SCN2A mutation results in Ohtahara syndrome in half siblings

Ayelet Zerem, Dorit Lev, Lubov Blumkin, Hadassa Goldberg-Stern, Yael Michaeli-Yossef, Ayelet Halevy, Sara Kivity, Kazuyuki Nakamura, Naomichi Matsumoto, Esther Leshinsky-Silver, Hirotomo Saitsu, Tally Lerman-Sagie

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31 Scopus citations


Ohtahara syndrome is a devastating early infantile epileptic encephalopathy caused by mutations in different genes. We describe a patient with Ohtahara syndrome who presented on the first day of life with refractory tonic seizures and a suppression-burst pattern on EEG. The patient developed severe microcephaly, and never achieved any developmental milestones. He died at the age of 5 years. A de novo missense mutation (c. 4007C>A, p.S1336Y) in SCN2A was found. Interestingly, the father has another son with Ohtahara syndrome from a different mother. The half brother carries the same SCN2A mutation, strongly suggesting paternal gonadal mosaicism of the mutation. The broad clinical spectrum of SCN2A mutations now includes Ohtahara syndrome. This is the first report of familial Ohtahara syndrome due to a germline mosaic SCN2A mutation. Somatic mosaicism, including germline, has been described in several epileptic encephalopathies such as Dravet syndrome, KCNQ2 neonatal epileptic encephalopathy, SCN8A epileptic encephalopathy and STXBP1 related Ohtahara syndrome. Mosaicism should be considered as one of the important inheritance patterns when counseling parents with a child with these devastating diseases.

Original languageEnglish
Pages (from-to)567-571
Number of pages5
JournalEuropean Journal of Paediatric Neurology
Issue number5
StatePublished - Sep 2014
Externally publishedYes


FundersFunder number
Japan Society for the Promotion of Science26860781


    • Channelopathies
    • Early infantile epileptic encephalopathy
    • Genetic counseling
    • Mosaic mutation
    • Suppression-burst


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