Phenotype and genotype analysis of 2 cases of congenital muscular dystrophy with carly rigid spine caused by SEPN1 mutation

Objective To analyze the clinical features of congenital muscular dystrophy with early rigid spine(rigid spine with muscular dystrophy type 1, RSMD1), and study the gene mutation. Methods Clinical data of the probands and the parents of 2 cases RSMD1 were collected.Skeletal muscle biopsies were performed on the probands for pathological diagnosis.Genomic DNA was extracted from peripheral blood leucocytes, and the virulence gene was detected by exon trapping and next generation sequencing technology to determine the gene mutation and confirm the pathogenicity. Results Two patients were presented with delayed motor development, a myopathic face, high palatine arches, and muscle weakness, hypotonia, with normal or mildly increased serum creatine kinase(CK) level.Case 1 was a 4 years old girl.She had neck extensor weakness, koilosternia, lordosis, repeat pulmonary infection, slightly high serum CK level, muscle MRI presented diffuse involvement and muscle biopsy had less significant pathological changes.Case 2 was a 13-year-old boy.He had scoliosis and respiratory insufficiency.His muscle biopsy indicated chronic myopathic changes with normal serum CK level.SEPN1 gene analysis results showed they had unreported compound heterozygote mutations, c.7_8insGGGCC(p.Arg5Glyfs), c.1167delC(p.His389fs) and c. 233delC(p.Ser78fs), c.1384T>C(p.Sec462Arg) respectively.The mutations in 2 patients were inherited from their parents respectively, and all were unreported novel mutations. Conclusions Two cases of RSMD1 are genetically identified and genetic counseling of the family can be possible.Patients, who have delay in motor milestone with cervicoaxial weakness early in life, spinal stiffness without limb joint contractures, progressive respiratory insufficiency, early nocturnal hypoventilation in a person who is still ambulatory, should be considered to detect SEPN1 mutation.Genetic analysis is the most reliable method for diagnosing RSMD1. Key words: Congenital muscular dystrophy with early rigid spine; Spinal rigidity; SEPN1 gene; Selenoprotein N