Four individuals from unrelated consanguineous families, two of European origin, one of Khmer origin and one of Middle Eastern origin all presented with congenital myopathy with:
- neonatal hypotonia, difficulty sucking, cleft palate, club feet ;
- generalized weakness predominantly in the lower limbs;
- myopathic facies, bilateral ptosis, ophthalmoplegia and fatigability;
- muscle biopsy revealed a predominance of type 1 fibers, slightly reduced triads and sarcoplasmic reticulum abnormalities;
- genomic analysis revealed homozygous loss-of-function variants of the JPH1 gene, which encodes junctophilin 1, a protein that connects T-tubules and the sarcoplasmic reticulum to form triads.
