A Review of Three Chinese Cases of Acromicric/Geleophysic Dysplasia with FBN1 Mutations

Abstract

Objective: This study aims to explore the clinical features and molecular diagnosis of FBN1-related acromelic dysplasia in Chinese patients.

Methods: The clinical and genetic features of three FBN1-related acromicric dysplasia (AD)/geleophysic dysplasia (GD) Chinese patients from two families were reviewed, and comprehensive medical evaluations were performed. Targeted next-generation sequencing was used to detect genetic mutations associated with short statures, including FBN1. Sanger sequencing was used to determine the de novo mutation origin.

Results: Patient 1 presented with short stature, short and stubby hands and feet, mild facial dysmorphism, hepatomegaly, delayed bone age and beak-like femoral heads. Patient 2 and this patient's father merely presented with short stature, wide and short hands, and beak-like femoral heads. One novel mutation, c.5272G>T(p.D1758Y), and one known mutation, c.5183C>T(p.A1728V), were identified in these patients.

Conclusion: The clinical features varied among these patients. The variant c.5272G>T(p.D1758Y) is a novel mutation.

Keywords: FBN1; acromelic dysplasia; acromicric dysplasia; geleophysic dysplasia; short stature.

Figure 1

Clinical and radiological features of patient 1: (A) short stature and facial profile; (B) small hand and short fingers; (C) delayed bone age and cone shaped epiphysis; (D) beak-like femoral heads.

Figure 2

Clinical and radiological features of patient 2 and patient 3: (A–D) The presence of small hands, but without joint contracture; (E–G) The images of the left hand, pelvis and vertebral column of patient 2 revealed shortened tubular bones in the hands and beak-like femoral heads.

Figure 3

A novel heterozygous missense mutation in exon 42 of the FBN1 gene, c.5272G>T (p.D1758Y), was found in patient 1.

Figure 4

A heterozygous missense mutation, c.5183C>T (p.A1728V), was detected in exon 42 in patient 2 and the patient’s father patient 3.