Adult presentation of X-linked Conradi-Hünermann-Happle syndrome

Abstract

Conradi-Hünermann-Happle syndrome, or X-linked dominant chondrodysplasia punctata type 2 (CDPX2), is a genodermatosis caused by mutations in EBP. While typically lethal in males, females with CDPX2 generally manifest by infancy or childhood with variable features including congenital ichthyosiform erythroderma, chondrodysplasia punctata, asymmetric shortening of the long bones, and cataracts. We present a 36-year-old female with short stature, rhizomelic and asymmetric limb shortening, severe scoliosis, a sectorial cataract, and no family history of CDPX2. Whole exome sequencing (WES) revealed a p.Arg63del mutation in EBP, and biochemical studies confirmed a diagnosis of CDPX2. Short stature in combination with ichthyosis or alopecia, cataracts, and limb shortening in an adult should prompt consideration of a diagnosis of CDPX2. As in many genetic syndromes, the hallmark features of CDPX2 in pediatric patients are not readily identifiable in adults. This demonstrates the utility of WES as a diagnostic tool in the evaluation of adults with genetic disorders.

Keywords: EBP; cataract; chondrodysplasia punctata; ichthyosis.

Figure 1. Clinical phenotype of the patient

A. Asymmetric, rhizomelic limb shortening. B. Hypertelorism, upslanting palpebral fissures, midface hypoplasia. C. Ichthyosis of lower legs. D. Sectorial cataract of right eye. E. Frontal thoracic and lumbar spine radiograph, scoliosis. F. Lateral lumbar spine radiograph, posterior wedging of L4 vertebral body, presumed congenital. G. Lateral skull radiograph, midface hypoplasia. H. Frontal view of pelvis, shortening of femoral necks and greater trochanteric overgrowth (relatively large and cranially displaced greater trochanters). I. Frontal view of right hand, mild negative ulnar variance, no evidence of epiphyseal stippling.