Distal myopathies

Gene: SPTAN1

Green List (high evidence)

Comment on list classification: 14 unrelated families with SPTAN1-related distal myopathy have been reported in literature, harbouring heterozygous LoF variants in SPTAN1. Myopathy of lower limbs was accompanied by gait disturbance and feet abnormalities. Based on available evidence, this gene should be promoted to Green at the next update.

Created: 10 Feb 2026, 1:52 p.m. | Last Modified: 10 Feb 2026, 1:52 p.m.

Panel Version: 6.16

PMID: 40023774 De Winter et al., 2025
Report of 14 families with heterozygous LoF SPTAN1 variants and early-onset distal myopathy (9x de novo and 5x dominantly inherited). Exome seq detected 9 frameshift, 4 nonsense, and 1 splice-acceptor variant in SPTAN1. Individuals presented with gait disturbance and foot abnormalities, including pes cavus and distal arthrogryposis. Muscle biopsy revealed myopathic changes in 7 patients.

PMID: 40999194 Van de Vondel et al., 2026
Report a family affected with childhood onset distal muscle weakness with a heterozygous chromosome 9q34 deletion encompassing the SPTAN1 gene (method: Exome seq). The deletion segregated with disease in 4 individuals, and was non-penetrant in two. Affected individuals presented with distal weakness in lower limbs (4/4) as well as pes cavus and hammer toes (2/4) or Distal arthrogryposis (2/4). Electromyography, muscle MRI and muscle biopsy showed myopathic disease.
The deletion encompasses SPTAN1, DYNC2I2, and a part of GLE1. Authors pose that SPTAN1 deletion is responsible for disease, as DYNC2I2 and GLE1 are not predicted to be dosage sensitive. However, the effect of other genes being deleted cannot be decoupled.

SPTAN1 is not yet associated with distal myopathy in OMIM (accessed 10th Feb 2026).
Sources: Literature

Created: 10 Feb 2026, 1:49 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
distal myopathy, MONDO:0018949

Publications

• 40023774
• 40999194