Congenital muscular dystrophy

Gene: MCOLN1

Red List (low evidence)

Comment on list classification: Assigned red rating as the phenotype is suggestive of a muscle myopathy and is not confirmed dystrophy.

In addition, as this is a syndromic condition, with intellectual disability and ophthalmologic abnormalities being the most consistently reported phenotypes, with myopathy/dystrophy being a less consistently reported secondary feature, it is more appropriate for this gene to be tested through the Paediatric disorders superpanel as per National Genomic Test Directory recommendations (TD v9). The gene is already green on both the Intellectual disability and Likely inborn error of metabolism panels which are components of the the Paediatric disorders superpanel. The gene is also green on the Lysosomal storage disorder panel.

Created: 18 Jun 2026, 10:22 p.m. | Last Modified: 25 Jun 2026, 3:17 p.m.

Panel Version: 7.26

Comment on phenotypes: OMIM phenotype accessed on 18th June 2026

Created: 18 Jun 2026, 10:21 p.m. | Last Modified: 18 Jun 2026, 10:21 p.m.

Panel Version: 7.20

Mucolipidosis IV (ML4) is an autosomal recessive neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmologic abnormalities (OMIM:605248)                                                                                                          

PMID: 33454187 Zambon et al 2021 - Bangladeshi boy with consanguineous parents presented with delayed motor milestones, hypotonia and an elevated creatine kinase (CK) at 2.5 yo. Electromyography revealed a myopathy with no evidence of peripheral neuropathy. Muscle biopsy showed evidence of lysosomal storage with mild degeneration/regeneration, but no overt dystrophic changes. WGS found a homozygous null variant in MCOLN1 c.514C>T; p.(Arg172Ter). Both parents were heterozygous carriers of this variant.
The authors note that MCOLN1 analysis may not be included in congenital muscular dystrophy gene panels due to the lack of recognition of the clinical overlap.

Two other publications report cases with elevated creatine kinase in patients with homozygous variants in MCOLN1 and a myopathy, or suspected myopathy phenotype PMID:32604955 and PMID:42037965. Muscular dystrophy not mentioned in these cases.

Created: 16 Jun 2026, 9:58 p.m. | Last Modified: 18 Jun 2026, 10:20 p.m.

Panel Version: 7.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mucolipidosis IV, OMIM:252650; mucolipidosis type IV, MONDO:0009653

Publications

• 33454187

Green List (high evidence)

lysosomal diseases, raised CK clinically overlapping phenotype with CM/CMD

Created: 22 May 2026, 1:49 p.m. | Last Modified: 22 May 2026, 1:49 p.m.

Panel Version: 7.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 33454187