Different skeletal phenotypes in a mother and two daughters with short stature homeobox-containing haploinsufficiency

Haploinsufficiency of the short stature homeobox-containing (SHOX) gene causes Turner skeletal features such as short metacarpals, cubitus valgus, and Madelung deformity. We report the clinical findings of a Japanese family consisting of two daughters with SHOX haploinsufficiency (46, X, del(X) (p.22.3)) and their mother with 45,X [9]/ 46, X, del(X) (p22.3) [11] karyotype. Physical and auxological examinations revealed a mesomelic appearance, cubitus valgus, a short neck and short stature in the daughters, but on the other hand, only a short neck and short stature in the mother. Radiological studies indicated markedly curved radii in the daughters, but only mild curvature of the radii in the mother. Regular menstruation had taken place since the age of 12 yr in the elder daughter, but the mother had irregular menstruation and she had received fertility treatment for pregnancy. The different skeletal phenotypes of the mother and her daughters with SHOX haploinsufficiency might be due to the mild gonadal estrogen deficiency found in the mother, which was caused by mosaic Turner syndrome, and the phenotypic variability of SHOX haploinsufficiency.