Congenital Muscular Dystrophy Type 1A:a Case Report And Literature Review

Objective Congenital muscular dystrophy type 1A(CMD1A)is an autosomal recessive disorder caused by biallelic mutations of LAMA2 gene encoding laminin-?2(merosin).As a genetic neuromuscular disease in children with high disability rate,this condition is rarely reported in China thus far.The purpose of this study was to explore the clinical and genetic characteristics of pediatric patients with CMD1 A and to provide references for the diagnosis and treatment of this disease.Subjects and methods Clinical data of a pediatric patient suspected to have CMD1 A were collected,summarized and analyzed.Peripheral anticoagulant blood samples from the patient,his parents and two brothers were collected.Genomic DNA was extracted,and genes related to congenital myopathy were analyzed by high-throughput sequencing technology.Then the positive variants were confirmed by Sanger sequencing.Following that,the key words "Congenital muscular dystrophy type 1A(CMD1A)","LAMA2 gene","Laminin alpha 2(merosin)" were retrieved in the literature databases Wanfang,How Net,Weipu,Medline and Pub Med,to find the relevant reports published in the past 10 years,and then the clinical data of the CMD1 A patients with detailed clinical and genetic information were systematically reviewed.Results The sick child in this study was a male aged 19 months,with the clinical manifestations of delayed motor development and significantly increased serum levels of creatinine creatinase,transaminases and lactate dehydrogenase.Genetic analysis revealed compound heterozygous LAMA2 mutations,with c.7147C>T(p.ala2383Ter)from the mother being a reported nonsense variant while c.8551?8552ins AA(p.Ile2852 Argfs Ter2)from the father,an unreported frameshift mutation.A total of 46 pediatric cases with CMD1 A with detailed clinical data were collected by literature review,all showing motor development retardation and increased creatine kinase levels.In most cases,brain MRI showed abnormal paraventricular and subcortical white matter with high intensity on T1 and T2 imaging,but intelligence impairment and epileptic attacks were negative.On follow-up,most patients were found to have poor prognoses with sustained motor retardation,and a patient even died due to respiratory muscular atrophy when growing older.A total of 66 LAMA2 variants were detected in the 46 patients,andnull mutations such as nonsense,frameshift,exon deletion and slpice-site accounted for 86.4%of all the variants.Conclusions In this study,a pediatric patient with CMD1 A was diagnosed by clinical and genetic analysis.The identification of the novel variant c.8551?8552ins AA(p.Ile2852 Argfs Ter2)expanded the LAMA2 mutation spectrum and provided a genetic basis for the definite diagnosis of the disease.Literature review revealed that CMD1 A patients usually had early onset within 6months after birth,and was characterized by severe motor development retardation with elevated serum creatine kinase as well as paraventricular and subcortical white matter impairment on MRI;The causative LAMA2 variants demonstrated remarkable heterogeneity,but the majority were null variants;Without specific treatment,CMD1 A patients usually had poor long-term prognoses.