Congenital myopathy

Gene: DNM2

The "watchlist_moi" tag is added to this gene to review the MOI in light of any new evidence as there is one family reported with biallelic inheritance.

Created: 3 Apr 2023, 6:14 p.m. | Last Modified: 3 Apr 2023, 6:14 p.m.

Panel Version: 4.18

Biallelic variants in DNM2 gene was only reported in three siblings, born of consanguineous Pakistani parents and not from any unrelated patients. These siblings presented with Lethal congenital contracture syndrome 5 (MIM #615368) characterised by akinesia, joint contractures, hypotonia, skeletal abnormalities, and brain and retinal hemorrhages. Muscle biopsy and EMG showed myopathic features. Therefore, the MOI should be left as "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" until more cases with biallelic variants are reported.

Created: 3 Apr 2023, 6:10 p.m. | Last Modified: 3 Apr 2023, 6:10 p.m.

Panel Version: 4.15

Phenotypes
Lethal congenital contracture syndrome 5, OMIM:615368

Publications

• 23092955

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
Myopathy, centronuclear, 160150; Charcot-Marie-Tooth disease, axonal, type 2M, 606482

Publications

• 22396310

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

Green List (high evidence)

biallelic DNM2 variants were also described in three consanguineous patients with lethal congenital syndrome caractherised by akinesia, joint contractures, hypotonia, skeletal abnormalities, and brain and retinal hemorrhages. muscle biopsy and EMG showed myopathic features. in particular, muscle biopsy of one patient showed small rounded fibers with some centralized nuclei, suggestive of a congenital myopathy whereas biopsy of a 2nd patient showed atrophic fibers without obvious centralization of nuclei.

Created: 24 Mar 2023, 11:39 a.m. | Last Modified: 24 Mar 2023, 11:39 a.m.

Panel Version: 4.2

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myopathy, centronuclear, 160150; Charcot-Marie-Tooth disease, axonal, type 2M, 606482; lethal congenital syndrome

Publications

• 22396310
• 23092955

Green List (high evidence)

Comment when marking as ready: Missense mutations reported in both phenotypes (centronuclear myopathy and CMT)

Created: 2 Feb 2017, 11:41 a.m.

Many reported families / mutations. Only missense in centronuclear myopathy but one frameshift found in relation to CMT presentation. The majority appear to present in childhood / early adulthood but specific mutations p.Ala618Thr and p.Ser619Trp/Leu present in neonatal phase therefore appropriate for congenital panel.

Created: 26 Jan 2017, 10:38 a.m.

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

Phenotypes
Myopathy, centronuclear 160150

Publications

• PMID 22396310