Congenital muscular dystrophy and congenital myopathy

Gene: EMD

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Additional comments from reviewing GLHs: 'Skewed X inactivation can mimic XLR so it is safer from an analytical perspective to have MOI as hemizygous mutation in males, monoallelic mutations in females may cause disease'

Created: 2 May 2024, 3:45 p.m. | Last Modified: 2 May 2024, 3:45 p.m.

Panel Version: 0.229

Green List (high evidence)

Eleanor Williams (Genomics England Curator) reviewing this gene on the old GMS Congenital muscular dystrophy panel notes: 'Added the expert review tag because OMIM has the mode of inheritance as XLR but the reviewer Anna Sarkozy has suggested X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease'.

Created: 21 Dec 2023, 7:40 p.m. | Last Modified: 21 Dec 2023, 7:40 p.m.

Panel Version: 0.195

Comment on list classification: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood. There is sufficient evidence (>3 cases) for this gene to be promoted to green in the next major review.

Created: 21 Dec 2023, 7:36 p.m. | Last Modified: 21 Dec 2023, 7:36 p.m.

Panel Version: 0.194

EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.

Created: 21 Dec 2023, 7:35 p.m. | Last Modified: 21 Dec 2023, 7:35 p.m.

Panel Version: 0.193

Anna Sarkozy (Great Ormond Street Hospital) reviewing this gene on the old GMS Congenital muscular dystrophy panel notes (rated Green): 'patients with pathogenic variants in EMD present symptoms from early childhood and symptoms can overlap those seen in patients with congenital onset muscular dystrophy with weakness and atrophy of muscle, contractures of joints in upper and lower limbs from early childhood, cardiomyopathy. in view of this we would recommend adding this gene into the R79 panel for CMD.'

Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes: Emery Dreifuss muscular dystrophy, X linked

Mode of pathogenicity: Other

Created: 21 Dec 2023, 7:33 p.m. | Last Modified: 21 Dec 2023, 7:33 p.m.

Panel Version: 0.193

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Emery-Dreifuss muscular dystrophy 1, X-linked, OMIM:310300

Publications

• 21697856
• 31645980
• 31802929
• 34026875

Red List (low evidence)

Typically causes later onset muscular dystrophy

Created: 26 Jan 2017, 3:57 p.m.

Comment on list classification: See reviewer comments - demoted to red as variants in this gene have not been reported for congenital muscular dystrophy.

Created: 27 Jan 2017, 1:55 p.m.

Comment on list classification: Demoted from green to amber due to reviewer's comment.

Created: 19 Dec 2016, 12:40 p.m.

I don't know

not convincing that this produces congenital phenotypes although undoubtedly causes later onset ones.

Created: 19 Dec 2016, 11:47 a.m.

Phenotypes
Emery-Dreifuss muscular dystrophy 1, X-linked, 310300