Puffenberger et al. (2012) reported 3 patients from 3 different Amish sibships in Pennsylvania with a lethal neonatal neurologic disorder. Episodic jerking was apparent in utero. At birth, affected individuals had small heads (1.5-2.0 SD below normal), overlapping ... Puffenberger et al. (2012) reported 3 patients from 3 different Amish sibships in Pennsylvania with a lethal neonatal neurologic disorder. Episodic jerking was apparent in utero. At birth, affected individuals had small heads (1.5-2.0 SD below normal), overlapping cranial sutures, small or absent fontanels, and depressed frontal bones. The hands were fisted and there was extreme axial and limb rigidity. The infants showed poorly responsive focal jerks of the tongue, face and arms in a nearly continuous sequence throughout life. Neuroimaging was normal or showed mild hypoplasia of the frontal lobes. Electroencephalograms were characterized by bilateral medium-high voltage spikes over the temporal and central regions, frequent multifocal seizures, background slowing, and no posterior rhythm. The infants made no developmental progress, and all died of cardiopulmonary arrest before age 4 months. Neuropathologic examination of the brain of 1 child showed neuronal loss with microglial reaction primarily in the striatum and cerebral cortex, consistent with corticobasal degeneration.
By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome, Puffenberger et al. (2012) identified a homozygous truncating mutation in the BRAT1 gene (614506.0001). Two unrelated Old ... By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome, Puffenberger et al. (2012) identified a homozygous truncating mutation in the BRAT1 gene (614506.0001). Two unrelated Old Order Amish infants from different demes in Wisconsin and Kentucky with a similar phenotype were found to carry the same homozygous mutation. Two heterozygous carriers of this mutation were found among 201 Old Order Amish control samples, yielding a population-specific allele frequency of 0.50%.