Adult onset neurodegenerative disorder

Gene: SPTLC2

Green List (high evidence)

Comment on list classification: There are at least 10 unrelated patients reported with juvenile onset ALS with monoallelic variants in SPTLC2 (9 de novo, 1 familial case with demonstrated autosomal dominant inheritance). Based on the available evidence, this gene should be rated Green for Adult onset neurodegenerative disorder.

Created: 13 Oct 2025, 2:25 p.m. | Last Modified: 13 Oct 2025, 2:25 p.m.

Panel Version: 8.3

Monoallelic variants in SPTLC2 have been associated with juvenile-onset amyotrophic lateral sclerosis:

PMID: 38041679 Syeda 2024 - 6 unrelated patients with a recurrent de novo variant p.Glu260Lys - trio WES/WGS. Phenotype: early-childhood-onset spasticity, followed by rapidly progressive weakness involving upper and lower extremities, bulbar muscles, tongue fasciculations and eventual respiratory insufficiency. Onset: congenital - 4 years of age.

PMID: 38316966 Naruse 2024 - 2 unrelated Japanese families with early-onset ALS - p.Ala71Val, p.Met68Arg. Method: WES. Onset of symptoms: 22-31 years.

PMID: 38041684 Dohrn 2024 - 2 unrelated patients (one African American and one Turkish-Bulgarian) with the same de novo variant p.Met68Arg. Childhood onset. Method: WGS/WES +Sanger confirmation.

SPTLC2 is associated with Neuropathy, hereditary sensory and autonomic, type IC in OMIM (613640) - accessed 13th Oct 2025).

Created: 13 Oct 2025, 2:08 p.m. | Last Modified: 13 Oct 2025, 2:21 p.m.

Panel Version: 8.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neuropathy, hereditary sensory and autonomic, type IC, OMIM:613640; amyotrophic lateral sclerosis 27, juvenile, MONDO:0859529

Publications

• 38041684
• 38041679
• 38316966