Adult onset hereditary spastic paraplegia

Gene: GJA1

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.

Panel Version: 1.95

Green List (high evidence)

Progressive neurological symptoms are occasionally seen in ODDD due to degeneration of the white matter tracts and can include spastic paraplegia. Gait disturbances due to spasticity can be a presenting feature for which patients initially seek medical attention. Typically signs of spasticity arise in adulthood (PMID: 18660473; 22214631; 29927410; 31023660; 33190326; 33612672); however, several adolescent onset cases (PMID: 18660473; 31023660) have also been described and I could only find a single childhood-onset case with spasticity arising at age 8 (PMID: 29927410).

Overall there is enough evidence to rate as Green on the adult-onset HSP panel (>10 unrelated families reported in literature). I will seek further clinical opinion with regard to inclusion on the childhood-onset panel given the implications of carrier status being found incidentally for this primarily adult-onset condition.

Created: 1 Sep 2021, 10:50 a.m. | Last Modified: 1 Sep 2021, 11:10 a.m.

Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Oculodentodigital dysplasia, OMIM:164200

Publications

• 18660473
• 22214631
• 29927410
• 31023660
• 33190326
• 33612672

Green List (high evidence)

8 individuals from 5 families with oculodentodigital dysplasia presenting in adulthood with onset of spastic paraplegia and white matter changes on imaging.
Sources: Expert list

Created: 20 Sep 2020, 8:35 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hereditary spastic paraplegia; Oculodentodigital dysplasia, MIM#164200

Publications

• 31023660

Variants in this GENE are reported as part of current diagnostic practice