Ilana Hanes1, Mariya Kozenko2, David J A Callen3. 1. McMaster University, Hamilton, Canada. 2. Division of Genetics, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, Canada. 3. Division of Pediatric Neurology, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, Canada. Electronic address: dcallen@mcmaster.ca.
Abstract
OBJECTIVE: Lethal neonatal rigidity and multifocal seizure syndrome is a newly recognized genetic disorder associated with early onset of rigidity, multifocal epilepsy, developmental arrest, and early death. It is an autosomal recessive condition resulting from a mutation in the BRAT1 (BRCA1 [breast cancer-1]-associated ataxia telangiectasia mutated activator 1) gene. There are few cases in the literature, and all patients have died before age 2 years, most within the first 6 months of life. The objective of this report is to expand the phenotypic spectrum of BRAT1 disorders and propose new nomenclature for this condition. RESULTS: We describe a child with compound heterozygosity for mutations in BRAT1. Her neonatal course was unremarkable. Over the first year of life she was noted to have progressive global developmental delay, visual impairment, microcephaly, hypertonia, hyperreflexia, and seizures. No epileptiform discharges were seen on electroencephalogram. Serial magnetic resonance imaging of the brain showed progressive cerebellar and brainstem atrophy. Unlike previously described patients, our patient has gained a number of developmental skills and, at this time, is 3 years and 8 months old. CONCLUSION: Despite the name of this disorder, patients with lethal neonatal rigidity and multifocal seizure syndrome may not present until after the neonatal period and may have a much longer life span than previously reported. We suggest renaming the condition "BRAT1-associated neurodegenerative disorder" to avoid the assumptions associated with the original nomenclature and to encourage clinicians to consider this condition outside the neonatal period.
OBJECTIVE:Lethal neonatal rigidity and multifocal seizure syndrome is a newly recognized genetic disorder associated with early onset of rigidity, multifocal epilepsy, developmental arrest, and early death. It is an autosomal recessive condition resulting from a mutation in the BRAT1 (BRCA1 [breast cancer-1]-associated ataxia telangiectasia mutated activator 1) gene. There are few cases in the literature, and all patients have died before age 2 years, most within the first 6 months of life. The objective of this report is to expand the phenotypic spectrum of BRAT1 disorders and propose new nomenclature for this condition. RESULTS: We describe a child with compound heterozygosity for mutations in BRAT1. Her neonatal course was unremarkable. Over the first year of life she was noted to have progressive global developmental delay, visual impairment, microcephaly, hypertonia, hyperreflexia, and seizures. No epileptiform discharges were seen on electroencephalogram. Serial magnetic resonance imaging of the brain showed progressive cerebellar and brainstem atrophy. Unlike previously described patients, our patient has gained a number of developmental skills and, at this time, is 3 years and 8 months old. CONCLUSION: Despite the name of this disorder, patients with lethal neonatal rigidity and multifocal seizure syndrome may not present until after the neonatal period and may have a much longer life span than previously reported. We suggest renaming the condition "BRAT1-associated neurodegenerative disorder" to avoid the assumptions associated with the original nomenclature and to encourage clinicians to consider this condition outside the neonatal period.
Authors: Siddharth Srivastava; Heather E Olson; Julie S Cohen; Cynthia S Gubbels; Sharyn Lincoln; Brigette Tippin Davis; Layla Shahmirzadi; Siddharth Gupta; Jonathan Picker; Timothy W Yu; David T Miller; Janet S Soul; Andrea Poretti; SakkuBai Naidu Journal: Am J Med Genet A Date: 2016-06-09 Impact factor: 2.802
Authors: Zuzana Cihlarova; Jan Kubovciak; Margarita Sobol; Katerina Krejcikova; Jana Sachova; Michal Kolar; David Stanek; Cyril Barinka; Grace Yoon; Keith W Caldecott; Hana Hanzlikova Journal: Nat Commun Date: 2022-08-26 Impact factor: 17.694