Adult onset hereditary spastic paraplegia

Gene: SPTAN1

Comment on phenotypes: OMIM phenotypes accessed on 16-02-2026

Created: 16 Feb 2026, 2:21 p.m. | Last Modified: 16 Feb 2026, 2:21 p.m.

Panel Version: 6.7

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 5:08 p.m. | Last Modified: 10 Oct 2023, 5:08 p.m.

Panel Version: 3.19

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) reported with spastic paraplegia and supported by functional studies. Both autosomal dominant and autosomal recessive variants of this gene are implicated in spastic paraplegia and at least three cases are reported for both disorders.

Autosomal dominant disorder:

OMIM reports Developmental and epileptic encephalopathy 5 (OMIM #613477) as a phenotype for SPTAN1 variants. Spastic quadriplegia is one of the clinical manifestations that has been reported as part of this phenotype.

Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia, while it has also been reported in one year old male from PMID:22656320 and two patients from PMID:18065176. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (three families) were presented with complex HA/HSP, two were presented with complex HSP and one with pure HSP.

Autosomal recessive disorder:

PMID:31515523 reported two cases of juvenile/ adult-onset spastic paraplegia caused by compound heterozygous variants (p.Ala858Ser/ p.Ala1428Gly & p.Ala858Ser/ Met2330Ile). PMID:34526651 reported a female patient with juvenile/ adult-onset spastic paraplegia and was identified with homozygous missense variant p.Ile1388Val.
Sources: Literature

Created: 6 Feb 2023, 3:23 p.m. | Last Modified: 6 Feb 2023, 5:59 p.m.

Panel Version: 2.9

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064

Publications

• 18065176
• 20493457
• 22656320
• 31515523
• 34526651
• 35150594
• 36331550