Merosin缺乏性先天性肌营养不良1A型1例报告

Merosin-deficient congenital muscular dystrophy type 1A:a case report and literature review

目的探讨LAMA2基因突变致先天性肌营养不良的临床特点及诊断方法。方法回顾分析1例merosin缺乏性先天性肌营养不良1A型(MDC1A)患儿的临床资料。结果患儿男性,2岁2个月首次就诊。临床表现为精神运动发育迟缓,不能站立、行走,口齿不清。肌酸激酶显著升高;头颅磁共振提示双侧脑室前角、后角周围及半卵圆中心深部白质呈长T1长T2、FLAIR序列大片高信号影。基因检测显示患儿有分别源自父亲的剪接突变(c.4718-1G>A)、源自母亲的移码突变(c.4529delC),为复合杂合突变。查阅既往文献及数据库未见报道。根据ACMG指南,两种变异均判定为致病性变异,确诊为MDC1A。结论MDC1A为LAMA2基因突变所致,肌肉活检及LAMA2基因检测可明确诊断。本次发现的基因突变为首次报道,扩充了先天性肌营养不良的基因突变谱。

Objectives To explore the clinical characteristics and diagnostic methods of congenital muscular dystrophy caused by LAMA2 gene mutation. Methods The clinical data of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) in a child were retrospectively analyzed. Results The boy first visited the hospital at 2 years and 2 months of age. His clinical manifestations were psychomotor retardation, inability to stand and walk, and slurred speech. The levels of creatine kinase were significantly increased. MRI indicated that the white matter around the anterior and posterior horn of bilateral ventricles and the deep center of the centrum semiovale showed long T1, long T2 and FLAIR sequence high signal. Genetic testing revealed that the child had a complex heterozygous mutation which was splicing mutation derived from the father (c.4718- 1G>A) and frameshift mutation derived from the mother (c.4529delC). No such reports have been found in the literature and databases. According to the ACMG guidelines, both variants were considered pathogenic, and the child was diagnosed with MDC1A. Conclusions MDC1A is caused by LAMA2 gene mutation. Muscle biopsy and LAMA2 gene detection can make a definite diagnosis. The genetic mutations found in this study are reported for the first time and it expands the gene mutation spectrum of congenital muscular dystrophy.