Congenital myopathy

Gene: SPTAN1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of monoallelic SPTAN1 variants with early-onset distal myopathy. Hence, this gene can be promoted to green rating on this panel in the next GMS update.

Created: 9 Jun 2026, 7:40 p.m. | Last Modified: 9 Jun 2026, 7:40 p.m.

Panel Version: 7.52

PMID:40023774 (2025) reported 20 patients from 14 families with heterozygous LoF SPTAN1 variants and early-onset distal myopathy (9x de novo and 5x dominantly inherited). The age of onset was 0-5 years in 14 patients, 6-10 in two, 11-15 in one and not reported in three. Exome sequencing detected 9 frameshift, 4 nonsense, and 1 splice-acceptor variant in SPTAN1. All affected participants presented with early childhood onset of gait and foot abnormalities. In general, participants showed stable or very slowly progressive (9/20) distal muscle weakness involving the foot (19/20) and toe extensors (15/20). Muscle biopsy revealed myopathic changes in seven patients.

PMID:40999194 (2026) reported a family affected with childhood onset distal muscle weakness with a heterozygous chromosome 9q34 deletion encompassing the SPTAN1 gene, identified via exome sequencing. The deletion segregated with disease in four 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 09 June 2026).

Created: 9 Jun 2026, 7:38 p.m. | Last Modified: 11 Jun 2026, 2:58 p.m.

Panel Version: 7.61

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
distal myopathy, MONDO:0018949

Publications

• 40023774
• 40999194

Green List (high evidence)

multiple reports of (early) osnset distal myopathy

Created: 22 May 2026, 1:49 p.m. | Last Modified: 22 May 2026, 1:49 p.m.

Panel Version: 7.14

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 40999194
• 40023774