Congenital muscular dystrophy and congenital myopathy

Gene: RYR1

Emma Clement (Great Ormond Street Hospital)\ reviewing this gene on the old GMS Congenital muscular dystrophy panel (rated Red) notes: more typically a myopathy presentation but there are several reports of RYR1 mutations in CMD like presentations so should probably be included. early scoliosis facial weakness +/- ophthalmoplegia

Created: 6 Feb 2023, 10:57 a.m. | Last Modified: 6 Feb 2023, 10:57 a.m.

Panel Version: 0.132

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
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000; Malignant hyperthermia susceptibility 1 145600

Publications

• 26799446

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000; Malignant hyperthermia susceptibility 1 145600

Publications

• 26799446

Green List (high evidence)

Comment when marking as ready: Clear evidence of causation. AD and AR inheritance

Created: 3 Feb 2017, 11:18 a.m.

Comment on mode of inheritance: Caution re malignant hyperthermia susceptibility (even in unaffected carriers). Potentially actionable

Created: 3 Feb 2017, 11:17 a.m.

Comment on list classification: RYR1 a recognised cause of central core disease. Tagged as pharmacogenetic / treatable in view of the need to highlight risk of MHS (malignant hyperthermia susceptibility) in affected individuals and potentially unaffected carriers

Created: 3 Feb 2017, 11:16 a.m.

Well established causal role with congenital myopathy associated with central cores. AR or AD inheritance. Important to recognise that phenotype of RYR1 mutations can also include Malignant Hyperthermia susceptibility, which could also be of clinical relevance to healthy carriers where AR inheritance is relevant within the family.

Created: 30 Jan 2017, 11:27 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000

Publications

• PMID 26799446