Eur J Med Genet. 2025 Dec;78:105057. doi: 10.1016/j.ejmg.2025.105057. Epub 2025 Oct 25.
ABSTRACT
Myopathic Ehlers-Danlos syndrome (mEDS) is a rare connective tissue disorder caused by pathogenic variants in COL12A1. It is characterized by congenital muscle hypotonia, muscle atrophy, and age-related improvement. We report the first detailed adult patient of mEDS with a novel compound heterozygous COL12A1 variant, complicated by Chiari I malformation and hydrocephalus. The patient presented with neonatal hypotonia, delayed motor milestones, scoliosis, and joint hypermobility, yet achieved independent ambulation. Muscle biopsy and immunostaining revealed markedly decreased levels of collagen XII. RNA sequencing demonstrated near absence of the long isoform and residual expression of the short isoform, potentially underlying the patient's clinical improvement. This is the first report to clarify the mechanism of preserved motor function in mEDS using RNA sequencing and immunostaining. Chiari I malformations may help distinguish mEDS from COL6-related disorders.
PMID:42046911 | DOI:10.1016/j.ejmg.2025.105057