Childhood onset dystonia, chorea or related movement disorder

Gene: SLC6A5

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants with hyperekplexia. As reviewed by Hannah Robinson, other hyperekplexia-causing genes (e.g. GLRA1 & GLRB) are rated green on this panel. Hence, this gene should be promoted to green rating in the next update.

Created: 23 Apr 2026, 11:59 a.m. | Last Modified: 23 Apr 2026, 11:59 a.m.

Panel Version: 7.23

PMID:16751771 (2006) reported seven patients from six unrelated families presenting with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnoea episodes. Of these, six patients from five families were identified with homozygous or compound heterozygous variants in SLC6A5 gene. The seventh patient was identified with a heterozygous variant in the same gene. There is also functional evidence available for the variants, showing that they result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites.

PMID:22753417 (2012) reported the identification of a new dominant SLC6A5 variant (p.Tyr705Cys) via single gene sequencing in eight individuals from three families in two cohorts of hyperekplexia patients. As well as classical hyperekplexia symptoms, certain individuals exhibited abnormal respiration, facial dysmorphism, delayed motor development, or intellectual disability. This may be due to a complex phenotype caused by the variant or to the presence of additional unknown variants. There is also functional evidence available for this variant.

Both monoallelic and biallelic variants are associated with hyperekplexia 3 (MIM #614618) in OMIM (last accessed 23 April 2026). But, only biallelic variants are associated with phenotypes in Gene2Phenotype and ClinGen.

Created: 23 Apr 2026, 11:54 a.m. | Last Modified: 23 Apr 2026, 11:54 a.m.

Panel Version: 7.20

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Hyperekplexia 3, OMIM:614618; hyperekplexia 3, MONDO:0013827

Publications

• 16751771
• 22753417

Green List (high evidence)

OMIM: 614618. Other hyperekplexia genes already included on the panel. Suitable for inclusion as a movement disorder.

Created: 16 Apr 2026, 7:58 a.m. | Last Modified: 16 Apr 2026, 7:58 a.m.

Panel Version: 7.20

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
hyperekplexia

Variants in this GENE are reported as part of current diagnostic practice

I don't know

?movement disorder

Created: 9 Jul 2019, 4:24 p.m. | Last Modified: 9 Jul 2019, 4:24 p.m.

Panel Version: 0.9