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

Abstract

Identification of a novel compound heterozygous of GNB5 in a patient with intellectual developmental disorder with cardiac arrhytmia (IDDCA), from non-consaguineous family. Three-dimensional modelling and in silico predictions suggest that GNB5 variants are causative of the phenotype, extending the number of IDDCA patients so far identified.

The epileptology of GNB5 encephalopathy

“…Homozygosity for the same missense variant has been seen in three families with nonepileptic, milder phenotypes, with either speech delay or mild intellectual disability. 3,5 In both cases there was significant developmental delay at 1 year of age. 1 Of interest, two recently reported children who were compound heterozygous for frameshift and missense variants had an intermediate phenotype.…”

“…1 Of interest, two recently reported children who were compound heterozygous for frameshift and missense variants had an intermediate phenotype. 3,5 In both cases there was significant developmental delay at 1 year of age. Neither child had seizures, but one had an abnormal EEG showing multifocal sharp waves.…”

“…1,4 Two siblings without seizures were homozygous for a variant that was predicted to affect splicing, but this was not proven in vitro. 3 Two of our nine cases had atypical seizure presentation: Patient 5 had a single episode of status epilepticus; | e127 POKE Et al. 3,5 In both cases there was significant developmental delay at 1 year of age.…”

“…Neither child had seizures, but one had an abnormal EEG showing multifocal sharp waves. 3 Two of our nine cases had atypical seizure presentation: Patient 5 had a single episode of status epilepticus; | e127 POKE Et al.…”

“…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. A milder cognitive phenotype without seizures is seen in individuals with nontruncating mutations.…”