Muscular dystrophy and myopathy_Paediatric
Gene: CACNA1S
At least 5 families with biallelic variants and 3 families with monoallelic missense variants (mainly de novo) with congenital myopathy. A decrease in protein level and a major impairment of Ca2+ release induced by depolarization in cultured myotubes was identified in both the dominant and recessive families. Thus, loss of function is the mechanism of disease for CACNA1S-related congenital myopathy.
Sources: Expert listCreated: 10 May 2023, 2:27 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Congenital myopathy MONDO:0019952
Publications
Variants in this GENE are reported as part of current diagnostic practice
11 patients from 7 families reported with perinatal hypotonia and weakness. AR / AD inheritance observed, PMID 28012042Created: 15 Jun 2020, 8:51 a.m. | Last Modified: 15 Jun 2020, 8:51 a.m.
Panel Version: 0.185
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Myopathy, congenital, due to dihydropyridine receptor defect, MIM# 620246
Publications
PMID: 32104981 - 1 Japanese family with consistent childhood onset hypokalemic periodic paralysis. The proband manifested symptoms at 6 years old and her children at 4- and 2 years of age. Motor and language development normal.
PMID: 19118277 - Arg mutations within the S4 segments are enriched in this gene, including recurring mutations p.Arg528Gly, p.Arg528His, p.Arg1239Gly and p.Arg1239His. One patient with a novel missense was specifically noted as having onset "in the second decade".
PMID: 31380823 - 1 patient with onset at 14 years old following vigorous exercise
PMID: 30325262 - 5 patients with adult onset myopathy (60-80 years old). Some have reported skeletal muscle defects.
PMID: 30319441 - describes both LOF and GOF mechanisms for this gene
Summary: a wide age of onset but multiple paediatric reports.
Sources: Expert listCreated: 15 Jun 2020, 3:47 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Hypokalemic periodic paralysis, type 1 170400
Publications
Mode of pathogenicity
Other
Gene: cacna1s has been classified as Green List (High Evidence).
Gene: cacna1s has been classified as Green List (High Evidence).
gene: CACNA1S was added gene: CACNA1S was added to Muscular dystrophy_Paediatric. Sources: Expert list Mode of inheritance for gene: CACNA1S was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CACNA1S were set to 28012042; 31227654; 33060286 Phenotypes for gene: CACNA1S were set to Congenital myopathy MONDO:0019952 Review for gene: CACNA1S was set to GREEN gene: CACNA1S was marked as current diagnostic