Lethal neonatal rigidity and multifocal seizure syndrome--report of another family with a BRAT1 mutation

Eur J Paediatr Neurol. 2015 Mar;19(2):240-2. doi: 10.1016/j.ejpn.2014.11.004.

Rachel Straussberg ¹, Esther Ganelin-Cohen ², Hadassah Goldberg-Stern ³, Shay Tzur ⁴, Doron M Behar ⁵, Pola Smirin-Yosef ⁶, Mali Salmon-Divon ⁷, Lina Basel-Vanagaite ⁸

Affiliations

1 Neurgenetics Clinic, Department of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: [email protected].
2 Neurgenetics Clinic, Department of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
3 Neurgenetics Clinic, Department of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
4 Molecular Medicine Laboratory, Rambam Health Care Campus, Haifa, Israel.
5 Raphael Recanati Genetics Institute, Rabin Medical Center, Petach Tikva, Israel; Molecular Medicine Laboratory, Rambam Health Care Campus, Haifa, Israel.
6 Felsenstein Medical Research Center, Petach Tikva, Israel; Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
7 Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
8 Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Raphael Recanati Genetics Institute, Rabin Medical Center, Petach Tikva, Israel; Felsenstein Medical Research Center, Petach Tikva, Israel.

PMID: 25500575 DOI: 10.1016/j.ejpn.2014.11.004

Abstract

We describe two siblings born to consanguineous Arab-Muslim parents who presented in early infancy with myoclonic seizures, hypertonia and contractures, arrested head growth, inability to swallow, and bouts of apnea-bradycardia, culminating in cardiac arrest and death. Whole-genome sequencing yielded a c.1173delG mutation in the BRAT1 gene. Three recent reports identified mutations in the same gene in three infants from three Amish sibships, one Mexican neonate and two Japanese siblings with similar clinical manifestations. The authors speculated that the destabilization of the encoded protein may underlie the catastrophic epilepsy and corticobasal neuronal degeneration. We suggest that BRAT1 be added to the growing list of genes that are related to severe early infantile (neonatal) epileptic encephalopathy.

Keywords

Apnea; Bradycardia; Epilepsy; Hypertonicity; Infancy; Seizures.

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