Congenital muscular dystrophy and congenital myopathy

Gene: ACTN2

Green List (high evidence)

As reviewed by Zornitza Stark (Australian Genomics), there is only one case with evidence of congenital onset of myopathy. But, we should note that the onset of symptoms in some congenital myopathies can be in childhood, even in late childhood. Hence, there are two unrelated cases and supporting functional evidence available to support the Green rating for this gene.

The biallelic cases are reported with distal myopathy (MIM #618655). Hence, the MOI should still remain as monoallelic in this panel.

Created: 26 Dec 2023, 4:44 p.m. | Last Modified: 26 Dec 2023, 4:44 p.m.

Panel Version: 0.218

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital myopathy 8, OMIM:618654

Publications

• 30701273

Now also report of three families with bialellic variants.

Created: 28 Nov 2021, 1:43 p.m. | Last Modified: 28 Nov 2021, 1:43 p.m.

Panel Version: 2.68

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• PMID: 34471957

I don't know

Gene causes a number of phenotypes. Evidence for congenital onset of myopathy is limited to one family. Second family proband described as having onset in childhood with physical difference noticed at 7 years old, later progressing to muscle atrophy and facial weakness at 40 years old. More recent report of another three families, but all with adult onset disease.

Created: 10 Jun 2020, 8:37 p.m. | Last Modified: 10 Jun 2020, 8:37 p.m.

Panel Version: 2.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, congenital with structured cores and Z-line abnormalities 618654; Myopathy, distal, 6, adult onset 618655

Publications

• 30701273
• 30900782

Green List (high evidence)

2 variants in this gene found in 2 unrelated families were presented as oral communication the World Muscle society meeting in Argentina. the functional data presented would suggest that variants in this gene are disease causing. this result is now published Acta Neuropathol. 2019 Mar;137(3):501-519.

Created: 30 May 2019, 4:32 p.m.

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

Publications

• 30701273

I don't know

Comment on list classification: Upgraded from Amber to Green. Appropriate phenotypes, sufficient cases (with functional work), and external review comment all support gene-disease association.

Created: 17 Oct 2019, 1:25 p.m. | Last Modified: 17 Oct 2019, 1:25 p.m.

Panel Version: 1.181

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.

I don't know

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

Phenotypes
Multiple structured Core Disease

Publications

• 24692096

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