Opsismodysplasia resulting from an insertion mutation in the SH2 domain, which destabilizes INPPL1.

Abstract

Opsismodysplasia (OMIM258480) is a rare, autosomal recessive skeletal dysplasia with delayed bone maturation. It was first described in 1977 by Zonana et al. and named opsismodysplasia by Maroteaux et al. in 1984 [Maroteaux et al., 1982; Maroteaux et al., 1984]. The clinical features include micromelia with extremely short hands and feet, as well as facial dysmorphism including prominent eyebrows, large open fontanels, depressed nasal bridge, short anteverted nose and relatively long philtrum. Some patients were also reported as having severe renal phosphate wasting [Below et al., 2013]. The characteristic radiographic features include severe platyspondyly, shortened long bones with dramatically delayed epiphyseal ossification, and characteristic hands with markedly delayed carpal ossification, short squared metacarpals and phalanges, and metaphyseal cupping [Beemer and Kozlowski 1994; Cormier-Daire et al., 2003; Maroteaux et al., 1984; Santos and Saraiva 1995; Tyler et al., 1999; Zonana et al., 1977]. The mortality is highly variable, ranging from death secondary to respiratory failure during the first few years of life to survival into adulthood.