颅骨下颌骨皮肤发育不全(mandibuloacral dysplasia，MAD)是一种罕见的常染色体隐性遗传疾病，主要与LMNA及ZMPSTE24基因发生变异有关。本文报道了国内首例颅骨下颌骨皮肤发育不全B型患者，主要表现为特殊面容、喂养困难、体格生长明显落后、全面的发育迟缓伴牙齿和骨骼发育异常。全外显子组家系测序结果显示患者携带ZMPSTE24基因c.743C>T (p.Pro248Leu) (dbSNP: rs121908095)与1~10号外显子缺失的复合杂合突变，经Sanger测序与定量聚合酶链反应(real-time quantitative PCR, RT-qPCR)实验检测显示，两个突变分别遗传自其表型正常的母亲与父亲。通过总结分析该例病例特点及其家系遗传规律，对于临床上难以进行明确诊断的疾病，建议进行全外显子组家系测序，辅助疾病的诊断。该病例的发现提高了临床医师对MAD疾病的认识，也为该疾病后续的遗传学研究提供新的临床资料。

Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder, mainly caused by pathogenic variants of the LMNA and ZMPSTE24 genes. In this study, we reported the first case of a patient with type B cranial and mandibular dysplasia in China. The patient presented with distinctive facial features, feeding difficulties, significant physical retardation, and overall developmental delay with abnormal tooth and bone development. Trio-whole exome sequencing analysis showed that the patient carried compound heterozygous mutations of c.743C>T (p.Pro248Leu) (dbSNP: rs121908095) and the loss of exons 1-10 of the ZMPSTE24 gene. Sanger sequencing and real-time quantitative PCR (RT-qPCR) showed that these two mutations were inherited from the patient’s phenotypically normal mother and father, respectively. By summarizing and analyzing the characteristics of this case and the pedigree of the family, we suggested that trio-whole-exome sequencing could be performed to assist in the diagnosis of diseases that are difficult to be diagnosed definitively based on clinical phenotypes. The publication of this case has improved clinicians’ understanding of MAD disease and provide new clinical information for the subsequent genetic study of this disease.