下颌骨肢端发育不良伴A型脂肪代谢障碍一家系报告并文献复习

Mandibuloacral dysplasia type A: a familial report and literature review

目的探讨LMNA基因突变所致下颌骨肢端发育不良伴A型脂肪代谢障碍(MADA)的临床特征。方法回顾分析1例LMNA基因纯合突变患儿的临床资料及其家系基因检测结果,并复习相关文献。结果女性先证者,7岁,重度矮小,特殊面容(圆脸、双眼睑色素沉着、喙状细鼻、口裂小伴牙列拥挤、咬合不正、牙齿发育不全),骨骼畸形(小下颌、双侧锁骨发育不全、指/趾末端短棒状),头发稀疏、无光泽,皮肤色素沉着、弹性差,指/趾甲发育不良,肘膝关节僵硬活动受限、下蹲不全,四肢及躯干皮下脂肪菲薄,肌力无异常,学习成绩优秀。患儿父母、姐姐表型正常,弟弟表现与先证者类似,但程度较轻。高通量测序分析发现患儿及其弟弟LMNA基因(NM-170707.3)存在纯合错义变异c.1580G>A,p.Arg527His;其父亲与母亲均携带该位点的杂合变异。结论 MADA有特征性的临床表现,基因检测可进一步明确诊断。

Objective To explore the clinical features of mandibuloacral dysplasia type A (MADA) caused by LMNA gene mutation. Methods The clinical data of LMNA homozygous mutation in a child and the results of gene detection in the family were retrospectively analyzed, and the related literature was reviewed. Results A 7-year-old girl suffered from postnatal growth restriction, specific facial features (round face, double eyelid pigmentation, beak-shaped nose, crack with crowded dentition, malocclusion, tooth hypoplasia), skeletal deformities (micrognathia, bilateral clavicle hypoplasia, short rod-shaped finger/toe end), sparse and lusterless hair, pigmented skin with poor elasticity, poor finger/toenail development, limited movement and incomplete squats due to stiff elbows and knees, thin subcutaneous fat of limbs and trunk, normal muscle strength, and excellent academic performance. The parents and the older sister of the child had normal phenotypes, and the younger brother had similar but less severe clinical manifestations. High throughput sequencing analysis revealed homozygous missense mutation c.1580G>A, p.Arg527His in the LMNA gene (NM-170707.3) of both the child and her younger brother, and heterozygous mutation of this locus was carried by both her parents. Conclusion MADA has characteristic clinical manifestations, and genetic testing can further confirm the diagnosis.