ESPE Abstracts

Background: Heterozygous alterations of SHOX and its regulatory region PAR1 are identified in approximately 70% of Léri-Weill dyschondrosteosis and 2–5% of idiopathic short stature cases. Identification of a SHOX mutation enables GH treatment to be offered to the patient.

Objective: To evaluate the clinical characteristics of seven patients with SHOX haploinsufficiency and their evolution.

Method: Retrospective analysis of patients with a genetic study of SHOX and the regulatory regions. Analysis of medical records.

Results: Seven patients: three girls, four boys. Average age at first visit 8.0 years (4.9–11.7). Referrals for short stature (seven). Personal history: SGA (two), preterm (one), obesity (one). Family history: short stature and alteration of body segments in parents (seven). Average target height −1.7 S.D.s (−1 to −2.1). Physical exam: mesomelic limb shortening (seven), Madelung deformity (two). Mean height at first consultation −2.75 S.D.s (−1.9 to −3.9). Radiological study: pathological in all patients. GH deficiency in three patients (two GH functional tests <10 ng/ml). GH treatment was initiated in four patients: mean inicial height −2.84 S.D.s (−2.1 to −4.1). Mean height after 1 year of treatment: −2.4 S.D.s (−1.75 to −3.28); mean increase 0.45 S.D.s (0.0 to 0.84); mean increase 7 cm/year (4–9.8). One patient, late onset: 12.3 years (bone age 13.0 and menarche a year earlier), increased 0.0 S.D.s and 4 cm in the 1st year. Mean height last consultation −2.36 S.D.s (−1.8 to −3.0). Genetic study: 3/7 presented with a heterozygous mutation, 1 stop mutation (c.79G>T (p.G27X)), two common 47.5 kb downstream enhancer deletions. Cosegregation of the mutation with the phenotype was confirmed when possible (two families).

Conclusion: The study of short stature should include a comprehensive physical examination to analyse body segments and skeletal dysplasias, requesting radiological study where appropriate. An early genetic study based on clinical suspicion (physical exam and family history) leads to early treatment with better response.