Hereditary ataxia

Gene: SCN8A

Green List (high evidence)

Comment on list classification: Upgraded from Red to Green - there is now a sufficient number of unrelated cases (>3) presenting ataxia in association with variants in the gene, supported by an animal model.

Created: 21 Jun 2021, 1:05 p.m. | Last Modified: 21 Jun 2021, 1:05 p.m.

Panel Version: 1.227

SCN8A is associated with a range of phenotypes including epilepsy, neurodevelopmental defects, and movement disorders. Some individuals with deleterious SCN8A variants develop ataxia - at least 14 individuals with ataxia reported in literature (see publications list). Variable age of onset - mostly during childhood but adult-onset cases have also been described. Mouse Scn8a mutants exhibit movement disorders including ataxia, tremor and dystonia.

Created: 21 Jun 2021, 1:04 p.m. | Last Modified: 21 Jun 2021, 1:10 p.m.

Panel Version: 1.228

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cognitive impairment with or without cerebellar ataxia, OMIM:614306; Developmental and epileptic encephalopathy 13, OMIM:614558

Publications

• 16236810
• 22365152
• 25725044
• 28702509
• 31675620
• 31887642

Comment on list classification: Single case and with inconclusive evidence in OMIM

Created: 4 Feb 2016, 2:27 p.m.

Red List (low evidence)

Not convincing - only a single family since 2006. Not on our panel. Mode of pathogenicity: loss-of-function/haploinsufficiency.

Created: 24 Nov 2015, 4:57 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cognitive impairment with or without cerebellar ataxia, 614306