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Congenital myopathy v7.77 MCOLN1 Eleanor Williams changed review comment from: 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.

However, as this is a syndromic presentation, 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. ; to: 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.
Congenital myopathy v7.77 MCOLN1 Eleanor Williams changed review comment from: 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.; to: 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.

However, as this is a syndromic presentation, 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.
Congenital myopathy v7.73 MCOLN1 Eleanor Williams Added comment: Comment on phenotypes: OMIM phenotype accessed on 18th June 2026
Congenital myopathy v7.73 MCOLN1 Eleanor Williams Phenotypes for gene: MCOLN1 were changed from to Mucolipidosis IV, OMIM:252650; mucolipidosis type IV, MONDO:0009653
Congenital myopathy v7.72 MCOLN1 Eleanor Williams Publications for gene: MCOLN1 were set to
Congenital myopathy v7.71 MCOLN1 Eleanor Williams Classified gene: MCOLN1 as Amber List (moderate evidence)
Congenital myopathy v7.71 MCOLN1 Eleanor Williams Added comment: 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.
Congenital myopathy v7.71 MCOLN1 Eleanor Williams Gene: mcoln1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v7.70 MCOLN1 Eleanor Williams edited their review of gene: MCOLN1: Changed rating: AMBER
Congenital myopathy v7.70 MCOLN1 Eleanor Williams changed review comment from: 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

Other publications that mention a myopathy phenotype in ML4 patients:

PMID: 32604955 Jezela-Stanek et al 2020
Report 2 Pakistani patients with adult onset myopathy both with homozygous MCOLN1 c.[1256G>C];p.(Arg419Pro), elevated creatine kinase and myopathy (no biopsy).; to: 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.
Congenital myopathy v7.61 MCOLN1 Eleanor Williams reviewed gene: MCOLN1: Rating: RED; Mode of pathogenicity: None; Publications: 33454187; Phenotypes: Mucolipidosis IV, OMIM:252650, mucolipidosis type IV, MONDO:0009653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v7.14 MCOLN1 Anna Sarkozy reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 33454187; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v7.9 MCOLN1 Arina Puzriakova Classified gene: MCOLN1 as No list
Congenital myopathy v7.9 MCOLN1 Arina Puzriakova Gene: mcoln1 has been removed from the panel.
Congenital myopathy v7.8 MCOLN1 Arina Puzriakova gene: MCOLN1 was added
gene: MCOLN1 was added to Congenital myopathy. Sources: NHS GMS
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal