Neurodegenerative disorders, adult onset

Gene: DYNC1H1

I don't know

DYNC1H1 is associated with a range of phenotypes including autosomal dominant axonal Charcot-Marie-Tooth disease type 2O (CMT2O, OMIM:614228) and autosomal dominant lower extremity-predominant spinal muscular atrophy-1 (SMALED1, OMIM:158600 (accessed 10/ 2026).

NHS England review is ongoing to determine whether DYNC1H1 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. To this end, although most reported CMT2O/SMALED1 cases have congenital, infantile or childhood manifestations, a biphasic disease course has been described across the broader DYNC1H1-related disorder spectrum, comprising developmental regression in the first decade, a period of relative stability and neurodegenerative progression after the second decade of life (Möller et al., 2024; PMID: 38848546).

Created: 6 Oct 2026, 4:35 p.m. | Last Modified: 6 Oct 2026, 4:35 p.m.

Panel Version: 9.23

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Charcot-Marie-Tooth disease, axonal, type 2O (OMIM:614228); Spinal muscular atrophy, lower extremity-predominant 1 (OMIM:158600)

Publications

• 38848546

Green List (high evidence)

Causes SMA-LED. While often childhood-onset, it can present or remain undiagnosed until adulthood, mimicking LMN-variant MND. Needs inclusion in R460.1 to avoid R78 reanalysis.

Created: 22 May 2026, 1:32 p.m. | Last Modified: 22 May 2026, 1:32 p.m.

Panel Version: 9.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Charcot Marie Tooth disease, axonal, type 20, 614228; Mental retardation, autosomal dominant 13, 614563; Spinal muscular atrophy, lower extremity predominant, AD, 158600

Publications

• 21820100
• 26392352

Mode of pathogenicity
Other

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

I don't know

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

Red List (low evidence)

Onset in early childhood

Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.

Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Charcot Marie Tooth, SMA, Intellectual disability