Ullrich先天性肌营养不良症合并多发骨折一例诊治研究及文献复习OA

Objective To analyse the clinical characteristics and pathogenic gene mutations in a rare case of Ull-rich congenital muscular dystrophy(UCMD)presenting from infancy with recurrent fractures under minimal force,scoliosis,muscle weakness and torticollis and to provide a reference for the diagnosis and treatment of this disease.Methods De-tailed clinical data were collected,including medical history and physical examination findings.Bone turnover markers and bone mineral density were measured and skeletal X-rays were used to assess bone deformity.Pathogenic gene mutations were validated via whole-exome sequencing,polymerase chain reaction(PCR),Sanger sequencing and bioinformatics analysis of variant pathogenicity.A review of relevant literature was conducted to summarize the genetic and phenotypic characteristics of UCMD patients.Results The patient was a 10-year-old girl who presented with recurrent fractures under minor trauma,joint laxity,congenital hip dislocation,hypotonia,torticollis and severe spinal deformity.Although bone turnover markers were normal,bone mineral density was markedly low.Radiographs revealed inter-sutural ossification and severe kyphotic spi-nal deformity.Genetic testing identified a heterozygous variant in the COL6A1 gene(c.904G＞A;p.Gly302Arg),confirming a diagnosis of UCMD with osteoporosis.Treatment with elemental calcium,calcitriol and denosumab for 28 months resulted in a significant reduction in bone resorption markers and an increase in bone mineral density.Subsequent scoliosis correction surgery resulted in an increase in the patient's height of 5.6 cm postoperatively.A literature review summarizing 74 cases of COL6A1 gene mutations revealed that the disease primarily presented with joint contractures(89.2%),joint laxity(81.1%),scoliosis(58.1%),hypotonia(56.8%),congenital hip dislocation(36.5%),delayed motor development(29.7%),respiratory insufficiency(21.6%)and congenital torticollis(9.5%).Genotype-phenotype correlation analysis revealed that missense mutations causing glycine substitution in type Ⅵ collagen was correlated with severe phenotypes.Conclusion As a rare hereditary disorder caused by COL6A1 gene mutations,UCMD primarily presents with joint contrac-tures,scoliosis and hypotonia,and is frequently accompanied by osteoporosis and multiple fractures.Detecting COL6A1 gene mutations helps to elucidate the molecular mechanisms of the disease,and denosumab could improve osteoporosis in UCMD patients.