SHOX haploinsufficiency and its modifying factors.

SHOX (short stature homeobox-containing gene) is the first gene that has been shown to be relevant to the development of specific features in Turner's syndrome. This article reviews clinical findings in patients with SHOX haploinsufficiency caused by intragenic mutations, pseudoautosomal submicroscopic deletions, and cytogenetically recognizable Xp deletions. SHOX haploinsufficiency can result in not only short stature but also Turner skeletal features, such as cubitus valgus, short metacarpals, Madelung deformity, Léri-Weill dyschondrosteosis, high arched palate, and short neck. Rare Turner skeletal features such as Madelung deformity and Léri-Weill dyschondrosteosis are primarily facilitated by the bone-maturing effect of gonadal estrogens. Common Turner skeletal features such as short metacarpals, cubitus valgus, and various craniofacial and cervical skeletal stigmata are largely caused by a compressive effect of distended lymphatics and lymphedema on the developing skeletal tissues.