Congenital myopathy

Gene: MCOLN1

I don't know

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

Created: 18 Jun 2026, 10:11 p.m. | Last Modified: 18 Jun 2026, 10:11 p.m.

Panel Version: 7.73

Comment on list classification: Rating amber based on 1 case with a confirmed myopathy and 2 further cases with elevated creatine kinase and myopathy features.

In addition, as this is a syndromic condition, with intellectual disability and ophthalmologic abnormalities being the most consistently reported phenotypes, with myopathy being 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, 10:10 p.m. | Last Modified: 25 Jun 2026, 3:13 p.m.

Panel Version: 7.77

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

1 case ( Zambon et al 2021) reported of a young child with ML4 and elevated creatine kinase, a myopathy confirmed by electromyography and a homogyzous truncating variant in MCOLN1. 2 other cases with elevated creatine kinase reported.

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

Other publications that mention a myopathy phenotype in ML4 patients:

PMID:32604955 Jezela-Stanek et al 2020
Report 2 Pakistani patients both with homozygous MCOLN1 c.[1256G>C];p.(Arg419Pro), elevated creatine kinase and myopathy (no biopsy reported) as part of their clinical features. One with congenital myopathy, other with no age of onset given but text suggests adult onset. Unclear if related or not.

PMID:42037965 Alsahlawi et al 2026
10-year-old boy from Bahrain with ML4 who presented with global developmental delay, spastic quadriparesis, severe visual impairment, gastrointestinal manifestations, and persistent elevation of creatine kinase (CK) suggestive of potential secondary myopathic involvement. No muscle biopsy reported. CK level first measured above normal at 1 year 3 months. WES identified a homozygous MCOLN1 variant (c.1336G>A; p.Val446Met). Parents were both heterozygous.

Created: 16 Jun 2026, 10:16 p.m. | Last Modified: 18 Jun 2026, 10:08 p.m.

Panel Version: 7.70

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: 7.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 33454187