Adult onset hereditary spastic paraplegia
Gene: GJA1The 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
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
8 individuals from 5 families with oculodentodigital dysplasia presenting in adulthood with onset of spastic paraplegia and white matter changes on imaging.
Sources: Expert listCreated: 20 Sep 2020, 8:35 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hereditary spastic paraplegia; Oculodentodigital dysplasia, MIM#164200
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_21_rating was removed from gene: GJA1.
Source Expert Review Green was added to GJA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: gja1 has been classified as Amber List (Moderate Evidence).
Tag Q3_21_rating tag was added to gene: GJA1.
Mode of inheritance for gene: GJA1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GJA1 were changed from Hereditary spastic paraplegia; Oculodentodigital dysplasia, MIM#164200 to Oculodentodigital dysplasia, OMIM:164200; Spastic paraplegia
Publications for gene: GJA1 were set to 31023660
gene: GJA1 was added gene: GJA1 was added to Hereditary spastic paraplegia - adult onset. Sources: Expert list Mode of inheritance for gene: GJA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GJA1 were set to 31023660 Phenotypes for gene: GJA1 were set to Hereditary spastic paraplegia; Oculodentodigital dysplasia, MIM#164200 Review for gene: GJA1 was set to GREEN gene: GJA1 was marked as current diagnostic