Arthrogryposis

Gene: MYH3

Comment on mode of inheritance: MOI should be changed from 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' at the next GMS panel update.

Monoallelic variants are associated with distal arthrogryposis conditions including Freeman-Sheldon syndrome and Sheldon-Hall syndrome.

Monoallelic and biallelic variants also underlie Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterised by extensive bony abnormalities in addition to congenital contractures - a phenotype relevant to this panel.

At least 3 unrelated recessive CPSFS cases have been reported with multiple contractures (PMID: 29805041). Additionally, two sibs from one family have been reported with distal arthrogryposis without additional features of CPSFS, who harboured two homozygous ultra-rare MYH3 variants (PMID: 38856159). Overall this evidence supports an MOI of 'both mono- and biallelic' on this panel.

Created: 31 Jul 2025, 9:29 a.m. | Last Modified: 31 Jul 2025, 9:29 a.m.

Panel Version: 9.3

Green List (high evidence)

38856159 reports also biallelic MYH3 variants as a cause of arthrogryposis, so probably should be updated to the biallelic inheritance as well.

Created: 15 Sep 2024, 3:11 p.m. | Last Modified: 15 Sep 2024, 3:11 p.m.

Panel Version: 7.2

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
arthrogryposis

Publications

• 38856159

Green List (high evidence)

Comment on mode of inheritance: Confirmed in G2P and OMIM.

Created: 3 May 2016, 9:54 a.m.

Comment on list classification: One green review, and a confirmed DD gene for distal arthrogryposis type 2A and distal arthrogryposis type 2B.

Created: 3 May 2016, 9:54 a.m.