Tian Fengyan, Dong Xiao, Yuan Ruyue, Hou Xiaohan, Qing Jing, Li Yani
Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Pediatr. 2024 Jul 15;12:1428513. doi: 10.3389/fped.2024.1428513. eCollection 2024.
Acromelic dysplasia caused by mutation includes acromicric dysplasia (AD), geleophysic dysplasia 2 (GD2), and Weill-Marchesani syndrome 2 (WMS2). All three diseases share severe short stature and brachydactyly. Besides phenotypic similarity, there is a molecular genetic overlap among them, as identical gene mutations have been identified in patients with AD, GD2, and WMS2. However, no family with different acromelic dysplasia phenotypes due to the same variant has been described in English reports.
The proband presented with typical facial features, severe short stature, short limbs, stubby hands and feet and radiological abnormalities. Her elder sister and mother had similar physical features. In addition, her elder sister was found to have aortic valve stenosis by echocardiography. Mutation analysis demonstrated a heterozygous missense mutation, c.5179C>T (p.Arg1727Trp) in exon 42 of the . The proband and her mother were diagnosed with AD, and her elder sister with GD2. The proband was treated with recombinant human growth hormone (rhGH) and had a body length gain of 0.72 SDS in half a year.
These findings expand the phenotypic spectrum of gene mutations and highlight that identical genotypes can result in different phenotypes of acromelic dysplasia in a family. The efficacy of rhGH therapy in patients with acromelic dysplasia is controversial. More follow-up is needed on the long-term efficacy of rhGH therapy.
由基因突变引起的肢端发育异常包括肢端短小发育异常（AD）、脂肪代谢障碍性发育异常2型（GD2）和魏尔-马歇沙尼综合征2型（WMS2）。这三种疾病均有严重身材矮小和短指（趾）畸形。除了表型相似外，它们之间还存在分子遗传学重叠，因为在AD、GD2和WMS2患者中已鉴定出相同的基因突变。然而，英文报道中尚未描述因同一变异导致不同肢端发育异常表型的家系。
先证者表现出典型的面部特征、严重身材矮小、四肢短小、手脚粗短及影像学异常。她的姐姐和母亲有相似的身体特征。此外，通过超声心动图发现她的姐姐有主动脉瓣狭窄。突变分析显示在该基因第42外显子中有一个杂合错义突变，c.5179C>T（p.Arg1727Trp）。先证者和她的母亲被诊断为AD，她的姐姐被诊断为GD2。先证者接受了重组人生长激素（rhGH）治疗，半年内身高增长了0.72 SDS。
这些发现扩展了该基因突变的表型谱，并强调相同的基因型可导致一个家系中出现不同的肢端发育异常表型。rhGH治疗肢端发育异常患者的疗效存在争议。需要对rhGH治疗的长期疗效进行更多随访。
