Acromicric dysplasia with stiff skin syndrome‐like severe cutaneous presentation in an 8‐year‐old boy with a missense FBN1 mutation: Case report and literature review

Abstract

BackgroundAcromicric 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.MethodsBy 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.ResultsThe 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.ConclusionThis 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.

A Case of Syncope in a Child due to the Large Segment of Myocardial Bridge

“…The result revealed a missense c.3525A to G (p.Ile1175Met) variant in the exon 29 of FBN1 gene, which was unreported previously. The occurrence of pathogenic variants in the FBN1 gene can cause Geleophysic dysplasia type 2, 9) Acromicric dysplasia, 10) Weill-Marchesani syndrome type 2, 11) Marfan syndrome, 12,13) and stiff skin syndrome 10) are all inherited in an autosomal dominant manner. Bioinformatics analysis suggested that the variant can cause amino acid replacement and affect the structure and function of fibrillin-1.…”

Separation in genetic pathogenesis of mutations in FBN1‐TB5 region between autosomal dominant acromelic dysplasia and Marfan syndrome

“…The rhGH treatment received by two of our patients confirmed its limited efficacy (de Bruin et al, 2016; Jin et al, 2017). Although the subtypes of acromelic dysplasia have been divided according to major disease‐specific symptoms such as ectopia lentis in WMS and cardiac valvular stenosis in GD, recent studies have shown that FBN1 mutations can lead to a mixed phenotype of both GD and AD (Cheng et al, 2017; Moey, Flaherty, & Zankl, 2019; Wang et al, 2020). Moreover, as these cases are identified during childhood, it could be too early to observe the full clinical spectrum (Marzin, Cormier‐Daire, & Dysplasia, 1993).…”

Classification and rising medication therapy in stiff skin syndrome: A case report and literature review

“…Attempted pharmacotherapy should be carefully performed, while LST and MPA may help to delay the progression of widespread SSS. Entities which ought not to be diagnosed as genuine SSS Parana hard-skin syndrome with visceral involvement, 28 FBN1 mutations presenting as Acromicric dysplasia combined with SSS-like features, 29 Marfan syndrome with SSS-like features, 14 and so forth Abbreviation: SSS, stiff skin syndrome.…”