Osteogenesis imperfecta type III/Ehlers-Danlos overlap syndrome in a Chinese man

Abstract

Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are rare genetic disorders that are typically inherited in an autosomal dominant manner. Few cases of OI/EDS overlap syndrome have been documented. Described here is a 30-year-old Chinese male with OI type III and EDS. Sequencing of genomic DNA revealed a heterozygous COL1A1 mutation (c.671G>A, p.Gly224Asp) that affected the N-anchor domain of the alpha 1 chain of collagen type I. Ultrastructural analysis of a skin biopsy specimen revealed thin collagen fibers with irregular alignment of collagen fibers. These findings have expanded the genotypic spectrum of the OI/EDS overlap syndrome.

Keywords: Ehlers-Danlos syndrome; collagen type I; osteogenesis imperfecta; transmission electron microscopy.

Figure 1.

Clinical and radiographic features of the patient. (A), The patient presented with an oval face, protuberant eyes, a short thorax, distinctive thoracic asymmetry, and dislocation of both radial heads; (B), Severe kyphoscoliosis; (C), Skin hyperextensibility; (D), Dislocation of the interphalangeal joints; (E), The femoral neck was thick and short, both femoral shafts were irregular, and tibial and fibular shafts on both sides were slender with expanded ends; (F), Bone structures were thin on both sides of the elbow, with some expansion at the epiphysis. The olecranon process was small, and subluxation of the elbow was also present.

Figure 2.

COL1A1 gene mutation and the structure and diameter of collagen fibers. (A), There is a heterogeneous G>A mutation (p.Gly224Asp) of COL1A1 in the patient but not in healthy family members; (B), Pedigree map of the patient; (C), Irregular fibers in the patient; (D) Collagen fibers with significantly smaller diameters in the patient.