Referenced in: none

Automatically associated channels: Kv7.2 , Nav1.6

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

Authors: 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

Journal, date & volume: Eur. J. Paediatr. Neurol., 2014 Sep , 18, 567-71

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24814476

Abstract
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.