Two unrelated patients with autosomal dominant omodysplasia and FRIZZLED2 mutations

Abstract

Presented are two patients with autosomal dominant omodysplasia and mutations in the FZD2 gene. The mutations identified have been recently reported, suggesting the possibility of recurrent mutations. The phenotypes of these patients overlap with what has been previously reported, though intellectual disability as seen in our patient is not typical.

Keywords: FRIZZLED2; omodysplasia; rhizomelia.

Figure 1

Patient 1 at age 52 years (left) and Patient 2 at 55 years (right top) and 63 years (right bottom). Note shortened upper extremities in both patients. Facial features of Patient 2 included a broad forehead, flat midface, broad nose with flat tip, anteverted nares, thick alae nasi, broad mouth, full lips, and broad chin. Palpebral fissures were narrow, upslanting, and hyperteloric. Interpupillary distance at age 57 years was measured at 7.5 cm (>97th centile). Subtle signs of midline clefting were noted including vertical furrowing in the glabellar region, a cleft in the chin, and a bifid tongue

Figure 2

A, The calvaria is thickened. B, C1 is hypoplastic and the odontoid process of C2 is partially bifid. C, Spinal stenosis is noted. D, The iliac wings are hypoplastic and the femoral necks are in mild valgus position. E, The humerus is short and proximally expanded with a distorted distal end and subluxed radial head. F, There is marked mesomelic shortness due to a short, club‐shaped ulna with a bowed radius. An osseous bridge connects the proximal ends of radius and ulna. G, The metacarpals are mildly short and plump. The proximal carpal bones small and deformed.