Neurodegenerative disorders, adult onset

Gene: MME

I don't know

MME is associated with a range of disorders including provisionally with autosomal dominant Spinocerebellar ataxia 43 (OMIM:617018) and autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease type 2T (CMT2T) (OMIM:617017) (accessed 10/2026).

Biallelic MME variants cause a late-onset distal hereditary motor neuropathy characterised by progressive distal motor weakness and wasting with minimal or absent sensory involvement (Hong et al. (2019), PMID 31429185), which, as reviewed by Oliver Ziff, could prompt consideration of an LMN-predominant MND phenotype. NHS England review is ongoing to determine whether MME falls within the intended scope of the adult-onset neurodegenerative disorders panel, based on its potential diagnostic utility as a lower-motor-neuron-variant MND mimic rather than an established association with adult-onset MND.

Created: 6 Oct 2026, 4:48 p.m. | Last Modified: 6 Oct 2026, 4:48 p.m.

Panel Version: 9.23

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
?Spinocerebellar ataxia 43 (OMIM:617018); Charcot-Marie-Tooth disease, axonal, type 2T (OMIM:617017)

Publications

• 31429185

Green List (high evidence)

MME variants frequently present as a late-onset >40 years motor-predominant axonal polyneuropathy. Because the clinical presentation features progressive distal lower motor neuron weakness and wasting in adulthood, it mimics Progressive Muscular Atrophy and LMN-variant MND. Adding it to the R460.1 panel is necessary to capture these mimics upfront and prevent sequential R78 WGS reanalysis for patients on the MND diagnostic pathway.
Sources: Expert Review, Literature

Created: 22 May 2026, 1:44 p.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Charcot-Marie-Tooth disease, axonal, type 2T, OMIM:617017

Publications

• 26924531

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

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