Congenital muscular dystrophy and congenital myopathy

Gene: MYH3

Green List (high evidence)

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 3:45 p.m. | Last Modified: 2 May 2024, 4 p.m.

Panel Version: 0.229

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

Comment on mode of inheritance: As reviewed by Anna Sarkozy, there is sufficient evidence for updating the MOI of this gene from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.

Created: 22 Dec 2023, 10:29 a.m. | Last Modified: 22 Dec 2023, 10:29 a.m.

Panel Version: 0.213

PMID:29805041 reported six patients from four unrelated families with compound heterozygous variants in MYH3 manifesting contractures in addition to the symptoms of Spondylocarpotarsal synostosis syndrome (SCTS).

PMID:32902138 reported four patients from two unrelated families with compounds heterozygous variants in MYH3 gene presenting with multiple pterygia, mild flexion contractures of several joints, and vertebral anomalies.

In addition, recessive variants in this gene has been associated with phenotypes in both OMIM (MIM #618469) and Gene2Phenotype.

All these evidences suggest that the MOI of this gene should be changed to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal".

Created: 22 Dec 2023, 10:28 a.m. | Last Modified: 22 Dec 2023, 10:28 a.m.

Panel Version: 0.210

Anna Sarkozy (Great Ormond Street Hospital) editing her previous review on this gene on the old GMS Congenital myopathy panel on 24 Mar 2023 notes (rated Green): 'Recessive MYH3 variants reported in patients with multiple pterygia and this disease entity is designated as "Contractures, pterygia, and variable skeletal fusions syndrome 1B," in OMIM.'

Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal

Phenotypes: Arthrogryposis, distal, type 2A 193700; Arthrogryposis, distal, type 2B 601680; Arthrogryposis, distal, type 8 178110; ontractures, pterygia, and variable skeletal fusions syndrome 1B

Publications: 18695058; 26578207; 32902138

Created: 22 Dec 2023, 10:27 a.m. | Last Modified: 22 Dec 2023, 10:27 a.m.

Panel Version: 0.210

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469

Publications

• 29805041
• 32902138

I don't know

Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.

Created: 30 Apr 2019, 10:09 a.m.

Green List (high evidence)

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

Phenotypes
Arthrogryposis, distal, type 2A 193700; Arthrogryposis, distal, type 2B 601680; Arthrogryposis, distal, type 8 178110

Publications

• 18695058
• 26578207

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

Green List (high evidence)

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

Phenotypes
Arthrogryposis, distal, type 2A 193700; Arthrogryposis, distal, type 2B 601680; Arthrogryposis, distal, type 8 178110

Publications

• 18695058
• 26578207

I don't know

Comment when marking as ready: Weakness is reported as part of the phenotype in some cases therefore appropriate to include.

Created: 22 Feb 2017, 11:09 a.m.

Comment on list classification: On reflection, although cases present with arthrogryposis, some of them had weakness and therefore the phenotype would be appropriate for inclusion. Discussed with Arianna Tucci for a second opinion who agrees.

Created: 22 Feb 2017, 11:08 a.m.

Comment when marking as ready: Sufficient unrelated families for causation, however, presentation is of arthrogryposis with or without myopathy. I cannot find evidence of myopathy in isolation and therefore considered more appropriate for arthrogryposis panel (green there already)

Created: 3 Feb 2017, 2:23 p.m.

Comment on list classification: Sufficient unrelated families for causation, however, presentation is of arthrogryposis with or without myopathy. I cannot find evidence of myopathy in isolation and therefore considered more appropriate for arthrogryposis panel.

Created: 3 Feb 2017, 2:20 p.m.

>4 unrelated families and therefore evidence of causation is satisfactory but main presentation is with arthrogryposis. However, some cases have been reported to have muscle weakness and delayed motor milestones.

Created: 31 Jan 2017, 11:05 a.m.

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

Phenotypes
Arthrogryposis, distal, type 2A 193700; Arthrogryposis, distal, type 2B 601680; Arthrogryposis, distal, type 8 178110

Publications

• PMID 18695058
• 26578207