SHOX haploinsufficiency: lessons from clinical studies

Abstract

SHOX (s hort stature h omeobo x-containing gene) is the first gene that has been shown to be relevant to the development of specific features in Turner syndrome. Clinical studies in individuals with SHOX haploinsufficiency caused by intragenic mutations, pseudoautosomal microdeletions, and cytogenetically recognizable Xp deletions have shown that SHOX haploinsufficiency causes not only short stature but also Turner skeletal features such as cubitus valgus, short metacarpals, Madelung deformity, high arched palate, and short neck, and that expressivity of SHOX haploinsufficiency in the limb and faciocervical regions is primarily influenced by gonadal function status and the presence or absence of the lymphogenic gene, respectively. The prevalence of SHOX haploinsufficiency is estimated as approximately 2% for idiopathic short stature and 60 to 80% for Léri-Weill dyschondrosteosis (LWD) characterized by Madelung deformity. Individuals with LWD and/or mesomelic short stature and familial members of a proband with SHOX haploinsufficiency should be examined for SHOX haploinsufficiency. Growth hormone and gonadotropin-releasing hormone analog may provide effective treatment for individuals with SHOX haploinsufficiency.