Bone Abstracts

Background: Weyers acrofacial dysostosis (WAD, OMIM 193530) is a rare autosomal dominant disease, characterized by mildly short stature, postaxial polydactyly, nail dystrophy and dental anomalies. WAD should be distinguished from Ellis-van Creveld syndrome (OMIM 225500), a similar but more severe disease, comprising chondrodysplasia, orofacial anomalies and, in a proportion of patients, cardiovascular malformations. Both diseases are caused by mutations in either EVC or EVC2^1,2. We report the case of a patient with WAD who presented altered bone metabolism and severe obesity.

Presenting problem: The patient came to our attention at age 6. He had presented postaxial hexadactyly of the hands and feet, surgically corrected when he was 2 years old. Other skeletal anomalies were short stature with short limbs, short terminal phalanges and mild retrognathia. Weight was above the 97th percentile. In addition, the patient had hypoplastic nails and dental anomalies (conical teeth, enamel hypoplasia, agenesis of permanent lower incisors). Electrocardiogram and echocardiography were normal. A previous array CGH was negative.

Clinical management: The phenotype was evocative of clinical spectrum of EVC-EVC2 mutations. Molecular analysis of EVC and EVC2 identified a heterozygous mutation in exon 22 of ECV2 gene (c.3805G>T). This mutation was not found in the child’s parents and it had been previously described in a single patient with WAD³. Therefore, the phenotype and the mutation were consistent with WAD. Regular endocrinological evaluations showed and confirmed altered bone quality (AD-SoS Z-score −3.99, BTT −2.80) and severe obesity with hyperinsulinism and insulin resistance.

Discussion: Our patient’s skeletal, nail and dental anomalies were typical of WAD. The mutation had been previously described in an Italian patient with WAD, whose clinical features were normal stature, postaxial polydactyly, hypoplastic nails, hypodontia, enamel hypoplasia, abnormally shaped teeth³. Altered bone density and severe obesity are not typical features in WAD and had not been described in the child with the same mutation. Our current finding expands the WAD clinical spectrum. Further studies are needed to demonstrate an association of altered bone density and severe obesity with the specific mutation of our patient.

Disclosure: The authors declared no competing interests.

References:
1. Online Mendelian Inheritance in Man, OMIM. Weyers acrofacial dysostosis; WAD. Number: 193530. Date last edited: 12/11/2014.

2. Ruiz-Perez VL, Goodship JA. Ellis–van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands. Am J Med Genet Part C Semin Med Genet 2009 151C 341–351.

3. D’Asdia MC, Torrente I, Consoli F et al. Novel and recurrent EVC and EVC2 mutations in Ellis-van Creveld syndrome and Weyers acrofacial dyostosis. European Journal of Medical Genetics. 2013 56 80–87.