Novel Clinical and Radiological Findings in a Family with Autosomal Recessive Omodysplasia

Abstract

Autosomal recessive omodysplasia (GPC6-related) is a rare short-limb skeletal dysplasia caused by biallelic mutations in the GPC6 gene. Affected individuals manifest with rhizomelic short stature, decreased mobility of elbow and knee joints as well as craniofacial anomalies. Both upper and lower limbs are severely affected. These manifestations contrast with normal height and limb shortening restricted to the arms in autosomal dominant omodysplasia (FZD2-related). Here, we report 2 affected brothers of Pakistani descent from Denmark with GPC6-related omodysplasia, aiming to highlight the clinical and radiological findings. A homozygous deletion of exon 6 in the GPC6 gene was detected. The pathognomonic radiological findings were distally tapered humeri and femora as well as severe proximal radioulnar diastasis. On close observations, we identified a recurrent and not previously described type of abnormal patterning in all long bones.

Keywords: GPC6; Omodysplasia; Radiological feature; Recessive omodysplasia; Skeletal dysplasia.

Fig. 1

A-E Skeletal survey of patient 1 after birth showing characteristic features of AR omodysplasia. Features include a broad and short diaphysis and either a distal or a proximal tapering of all long bones. The spine and pelvis were unremarkable (C).

Fig. 2

A-D Skeletal survey of patient 1 at 3 years of age showing the same radiological pattern as that previously seen after birth.

Fig. 3

A-D Skeletal survey of patient 2 at 6 months of age showing the same pattern as that of patient 1. The proximal tibia showed megaepiphyses at this age (C, D).