Hereditary neuropathy or pain disorder

Gene: SOD1

Green List (high evidence)

Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous SOD1 variants and hereditary neuropathy (motor and/ or sensory), often diagnosed as CMT disease. Sensory neuropathy may precede classical motor symptoms of ALS. Hence, SOD1 should be promoted to Green on Hereditary neuropathy or pain disorder at the next GMS update.

Created: 12 Mar 2026, 12:23 p.m. | Last Modified: 12 Mar 2026, 12:24 p.m.

Panel Version: 7.43

PMID: 39932579 Ando et al., 2025
17 Japanese patients with 10 different missense SOD1 variants and peripheral neuropathy with avg onset at 47 years. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy. Distal muscle weakness was noted in 9/13 patients, asymmetric muscle weakness and atrophy in 10/14, mild sensory disturbances observed in 8 patients, with some showing hyperreflexia and abnormal reflexes.

PMID: 36316849 Luo et al., 2022
Case report: 50yo female patient with hereditary motor and sensory neuropathy (CMT diagnosis). Presented with weakness of lower extremities. Heterozygous SOD1 c.140A>G, p(.His47Arg) was detected. Father with similar disease progression starting at age 50, not genotyped (deceased).

PMID: 22475618 Østern et al., 2012
Large Norwegian pedigree with hereditary neuropathy (diagnosis of CMT type 2), segregating with SOD1 c.140A>G, p.His47Arg variant.

PMID: 37610446 Bombaci et al., 2023 - literature review of ALS cases
Many authors reported an overlap of both sensory and motor symptoms in ALS patients. 20/29 ALS patients from case reports had sensory symptoms - common in spinal onset ALS. If sensory neuropathy precedes ALS there is usually a delay in ALS diagnosis.

SOD1 is linked to AD, AR Amyotrophic lateral sclerosis 1, OMIM:105400 & AR Spastic tetraplegia and axial hypotonia, progressive, OMIM:618598 (OMIM accessed 12th Mar 2026).
Sources: Literature

Created: 12 Mar 2026, 12:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Charcot-Marie-Tooth disease, MONDO:0015626; Amyotrophic lateral sclerosis 1, OMIM:105400

Publications

• 22475618
• 36316849
• 39932579