Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Mol Genet Genomic Med. 2020 Jul;8(7):e1282. doi: 10.1002/mgg3.1282. Epub 2020 May 14.
Acromicric dysplasia is a rare heritable short-stature syndrome with joint stiffness and varying degrees of cutaneous hardness. Stiff skin syndrome is a rare connective tissue disorder characterized by diffusely thick and hard skin from the time of birth. Heterozygous point mutations in the FBN1 have been proposed as the predominant cause of both diseases.
By performing skin biopsy, X-ray imaging, electrocardiography, as well as whole-genome sequencing and Sanger sequencing, we diagnosed an 8-year-old Chinese boy as acromicric dysplasia with severe skin stiffness caused by a heterogeneous mutation in the FBN1.
The patient presented with skin tightness, wrist and ankle stiffness, short stature and limbs, several deformed joints in the extremities, cone-shaped epiphyses, and distinct facial features. He also had a patent foramen ovale and frequent respiratory infections. Skin biopsy showed thickened dermis and excessive collagen aggregation. Alcian blue staining indicated dermal mucopolysaccharide deposition. Mutation analysis revealed a heterozygous missense mutation, c.5243G>A (p.Cys1748Tyr), in exon 42 of the FBN1.
This is a report about acromicric dysplasia with stiff skin syndrome-like severe cutaneous presentation caused by a single hotspot mutation, further revealing the gene pleiotropy of FBN1.
肢端矮小症是一种罕见的遗传性身材矮小综合征，伴有关节僵硬和不同程度的皮肤硬化。硬皮病综合征是一种罕见的结缔组织疾病，其特征是从出生时起皮肤弥漫性增厚和变硬。FBN1 中的杂合点突变被认为是这两种疾病的主要原因。
通过皮肤活检、X 射线成像、心电图以及全基因组测序和 Sanger 测序，我们诊断了一名 8 岁的中国男孩患有肢端矮小症，其 FBN1 存在异质性突变，导致严重的皮肤僵硬。
患者表现为皮肤紧绷、腕关节和踝关节僵硬、身材矮小和四肢短小、四肢多个畸形关节、锥形骨骺、明显的面部特征。他还存在卵圆孔未闭和频繁的呼吸道感染。皮肤活检显示真皮增厚和胶原过度聚集。阿辛蓝染色显示真皮黏多糖沉积。突变分析显示 FBN1 外显子 42 中存在杂合错义突变 c.5243G>A（p.Cys1748Tyr）。
这是一例肢端矮小症伴硬皮病综合征样严重皮肤表现的病例报告，由单一热点突变引起，进一步揭示了 FBN1 的基因多效性。
