GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability

The epileptology of GNB5 encephalopathy

“…7 We contacted clinicians of four previously reported patients with GNB5 pathogenic variants and epilepsy in whom there had been no or limited description of their epilepsy. 1 For each patient, we obtained a detailed seizure and medical history, examination findings, and magnetic resonance imaging (MRI) and electroencephalography (EEG) data. The New Zealand Health and Disability Ethics committee approved the study.…”

“…Eight children developed multiple seizure types including focal tonic (4), focal motor (3), tonic-clonic (3), focal autonomic (2), and tonic (1). Myoclonic, atonic, and absence seizures were not seen.…”

“…4 GNB5 knockout mice have impaired neurologic, cardiac, and retinal function. 1 Here we delineate the epileptology of GNB5 developmental and epileptic encephalopathy in five new and four previously reported patients, 1 enabling earlier recognition of GNB5 developmental and epileptic encephalopathy (DEE).…”

“…Biallelic pathogenic variants in GNB5 have recently been associated with an autosomal recessive neurodevelopmental disorder with sinus bradycardia and retinal dysfunction. 1 Twenty-two affected individuals from 10 families were reported in 2016-2018. [1][2][3][4][5] Homozygous and compound heterozygous truncating variants are found in a severe phenotype with hypotonia, visual loss, early onset sinus node dysfunction, epilepsy and profound impairment.…”

Intellectual developmental disorder with cardiac arrhythmia syndrome in a child with compound heterozygous GNB5 variants

“…3 Individuals at the milder and severe end of the GNB5-associated pathologies carry homozygous S81L and biallelic loss-of-function variants, respectively. [1][2][3] We describe a 2-year-old male proband compound heterozygote for GNB5 (NM_006578.…”