Ataxia - paediatric

Gene: RORA

Green List (high evidence)

11 unrelated individuals with syndromic intellectual disability and de novo variants in this gene. Severity varied from mild borderline intellectual disability with mild speech delay or normal speech, through to severe cognitive impairment with poor or absent speech. Most had ataxia, hypotonia, poor coordination, and/or mild tremor, suggesting cerebellar dysfunction. Three individuals had documented cerebellar hypoplasia or pontocerebellar atrophy on brain imaging. Seven had seizures of variable types, including neonatal myoclonic, tonic-clonic, multifocal, generalized, and absence. Five were diagnosed with autism spectrum disorder. More variable features included strabismus, esotropia, nystagmus, and oculomotor apraxia.

Postulated that some variants exert dominant-negative effect resulting in a more severe phenotype than the LoF variants.

Created: 12 Sep 2020, 7:32 a.m. | Last Modified: 12 Sep 2020, 7:33 a.m.

Panel Version: 0.251

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM# 618060

Publications

• 29656859