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Congenital myopathy v7.80 RYR3 Ida Ertmanska changed review comment from: PMID 29498452 Nilipour et al., 2018
Reported a 22yo female individual with nemaline myopathy and harboring two unique RYR3 missense variants. She presented at 5yo with muscle weakness. At 22yo she had facial weakness, mild scapular winging, proximal limb weakness, high arched palate, and micrognathia. Muscle strength was 4/5 and 5/5 in the limbs. EMG showed myopathic potentials. Muscle biopsy showed features consistent with nemaline myopathy.
WES identified comp het variants in RYR3: c.6208A>G, p.Met2070Val (MAF = 0.0007467 in gnomAD v4, no hmz) & c.8939G>T, p.Arg2980Leu (MAF=0.001644 in gnomAD v4, no hmz). Variants confirmed in trans, het parents unaffected.

PMID: 31230720 Pehlivan et al., 2019
Reported 3 unrelated individuals with biallelic RYR3 variants and arthrogryposis.
BAB7845 - homozygous for RYR3: c.2486G>A (p.Arg829His)
PAED187 - comp het for RYR3 c.2000A>G (p.Asp667Gly) & c.11164+1G>A
BAB8988 - homozygous for RYR3: c.8939G>T (p.Arg2980Leu)

Multiple other patients have been reported with mono- and bi-allelic RYR3 variants and developmental and epileptic encephalopathy (PMIDs:25262651; 29667327; 39220738; 39840699, and https://doi.org/10.1016/j.gendis.2026.102341). Partial phenotype overlap: some patients showed hypotonia, dystonia, motor dyspraxia (e.g., Xu et al., 2026).

Other studies reported RYR3 varians in patients with congenital heart disease: PMID: 39762984; PMID: 41022857.

The association between RYR3 and recessive congenital myopathy has been classified as Disputed in ClinGen in Oct 2025 (Congenital Myopathies Expert Panel). RYR3 is associated with AR Congenital myopathy 20, OMIM:620310 in OMIM (accessed 3rd Sept 2026).; to: PMID 29498452 Nilipour et al., 2018
Reported a 22yo female individual with nemaline myopathy and harboring two unique RYR3 missense variants. She presented at 5yo with muscle weakness. At 22yo she had facial weakness, mild scapular winging, proximal limb weakness, high arched palate, and micrognathia. Muscle strength was 4/5 and 5/5 in the limbs. EMG showed myopathic potentials. Muscle biopsy showed features consistent with nemaline myopathy.
WES identified comp het variants in RYR3: c.6208A>G, p.Met2070Val (MAF = 0.0007467 in gnomAD v4, no hmz) & c.8939G>T, p.Arg2980Leu (MAF=0.001644 in gnomAD v4, no hmz). Variants confirmed in trans, het parents unaffected.

PMID: 31230720 Pehlivan et al., 2019
Reported 3 unrelated individuals with biallelic RYR3 variants and arthrogryposis.
BAB7845 - homozygous for RYR3: c.2486G>A (p.Arg829His) - 6mo female with arthrogryposis multiplex congenita, hypotonia, facial dysmorphism. Comp het variants in MYO18B also detected.
PAED187 - comp het for RYR3 c.2000A>G (p.Asp667Gly) & c.11164+1G>A - female with bilateral clubfoot, finger contractures, GDD, enteropathy. She had repeated episodes resembling seizures around age 2 yrs - these resolved without treatment. No signs of muscle disease. CGH array detected a 144kb microdeletion in 6q22.31 of unknown significance.
BAB8988 - homozygous for RYR3: c.8939G>T (p.Arg2980Leu) - 15yo female with high arched palate, contractures, ulnar deviation, scoliosis. Parents are consanguineous.

Multiple other patients have been reported with mono- and bi-allelic RYR3 variants and developmental and epileptic encephalopathy (PMIDs:25262651; 29667327; 39220738; 39840699, and https://doi.org/10.1016/j.gendis.2026.102341). Partial phenotype overlap: some patients showed hypotonia, dystonia, motor dyspraxia (e.g., Xu et al., 2026).

Other studies reported RYR3 varians in patients with congenital heart disease: PMID: 39762984; PMID: 41022857.

The association between RYR3 and recessive congenital myopathy has been classified as Disputed in ClinGen in Oct 2025 (Congenital Myopathies Expert Panel). RYR3 is associated with AR Congenital myopathy 20, OMIM:620310 in OMIM (accessed 3rd Sept 2026).
Congenital myopathy v3.75 MYO18B Arina Puzriakova Phenotypes for gene: MYO18B were changed from Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549; Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, MONDO:0014689 to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549
Congenital myopathy v2.59 MYO18B Arina Puzriakova Publications for gene: MYO18B were set to 27879346; 27858739; 25748484; 32637634
Congenital myopathy v2.59 MYO18B Arina Puzriakova Publications for gene: MYO18B were set to 27879346; 27858739; 25748484
Congenital myopathy v2.28 MYO18B Arina Puzriakova Phenotypes for gene: MYO18B were changed from KLIPPEL-FEIL SYNDROME 4, AUTOSOMAL RECESSIVE, WITH NEMALINE MYOPATHY AND FACIAL DYSMORPHISM to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549; Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, MONDO:0014689
Congenital myopathy v1.120 MYO18B Rachael Mein edited their review of gene: MYO18B: Changed publications: 27879346, 27858739, 25748484; Changed phenotypes: KLIPPEL-FEIL SYNDROME 4, AUTOSOMAL RECESSIVE, WITH NEMALINE MYOPATHY AND FACIAL DYSMORPHISM
Congenital myopathy v1.76 MYO18B Louise Daugherty reviewed gene: MYO18B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v1.75 MYO18B Rachael Mein reviewed gene: MYO18B: Rating: GREEN; Mode of pathogenicity: ; Publications: 15322983; Phenotypes: Laing Distal Myopathy, 160500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital myopathy v1.74 MYO18B Louise Daugherty Source NHS GMS was added to MYO18B.
Congenital myopathy v1.73 MYO18B Louise Daugherty Source London South GLH was added to MYO18B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Congenital myopathy MYO18B Helen Brittain marked MYO18B as ready
Congenital myopathy MYO18B Helen Brittain commented on MYO18B
Congenital myopathy MYO18B Helen Brittain classified MYO18B as green
Congenital myopathy MYO18B Anna Sarkozy reviewed MYO18B