Neurodegenerative disorders, adult onset

Gene: PLEKHG5

I don't know

PLEKHG5 is associated with Charcot-Marie-Tooth disease, recessive intermediate C (OMIM:615376) and Neuronopathy, distal hereditary motor, autosomal recessive 4 (OMIM:611067) (accessed 10/ 2026).

As reviewed by Oliver Ziff, PLEKHG5-related disease can present in adulthood and/ or may enter an adult lower motor (LMN) disease or progressive muscular atrophy (PMA) diagnostic pathway because of overlapping clinical presentation, though review of the literature primarily supported a childhood-onset-PMA-like clinical presentation (PMID:17564964; 33275839). NHS England review is ongoing to determine whether PLEKHG5 falls within the intended scope of the adult-onset neurodegenerative disorders panel, based on potential diagnostic utility rather than a definitive association with adult-onset LMN/ PMA.

Created: 6 Oct 2026, 11:18 a.m. | Last Modified: 6 Oct 2026, 11:18 a.m.

Panel Version: 9.22

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Charcot-Marie-Tooth disease, recessive intermediate C (OMIM:615376; Neuronopathy, distal hereditary motor, autosomal recessive 4 (OMIM:611067)

Publications

• 17564964
• 33275839

Causes a late-onset distal hereditary motor neuropathy and SMA with progressive LMN signs that mimic PMA. Inclusion prevents sequential WGS reanalysis on R460.1 requests.
Sources: Expert Review, Literature

Created: 22 May 2026, 1:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Charcot Marie Tooth disease, recessive intermediate C, 615376; Spinal muscular atrophy, distal, autosomal recessive, 4, 611067

Publications

• 23844677
• 17564964

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments