Childhood onset hereditary spastic paraplegia

Gene: SOD1

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Created: 17 Oct 2025, 11:38 a.m. | Last Modified: 17 Oct 2025, 11:38 a.m.

Panel Version: 8.22

At least 10 individuals from 7 unrelated families have been identified with biallelic variants in the SOD1 gene and progressive spastic tetraplegia with age of onset before 2 years old. A recurrent variant (c.335dupG, p.Cys112Trpfs*11) was found in four apparently unrelated families of Afghan or Lebanese descent, while the other three families carried other homozygous LOF variants (c.357_357+2delGGT, c.52_56del5ins154, c.369_371del). Variants are predicted to lead to a completely non-functional enzyme product. The phenotype comprises early-onset progressive neuromuscular and developmental degeneration, leading to spastic tetraplegia and axial hypotonia. Most patients display global developmental delay (ranging from mild to profound cognitive impairment) and cerebellar atrophy. (PMIDs: 31314961; 31332433; 34380534; 34788402; 36935613; 39629626)

This gene is associated with a relevant phenotype in OMIM - Spastic tetraplegia and axial hypotonia, progressive, OMIM:618598 (accessed on 17-10-2025)
Sources: Literature

Created: 17 Oct 2025, 11:35 a.m. | Last Modified: 17 Oct 2025, 11:36 a.m.

Panel Version: 8.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic tetraplegia and axial hypotonia, progressive, OMIM:618598

Publications

• 31314961
• 31332433
• 34380534
• 34788402
• 36935613
• 39629626