Unique deletion in exon 5 of SHOX gene in a patient with idiopathic short stature.
OBJECTIVE
It is known that haploinsufficiency for the SHOX gene (short-stature homeobox gene on the X chromosome) is responsible for short stature in Turner syndrome and Leri-Weill dyschondrogenesis, and it has been reported that it is responsible for upwards of 1 in 50 cases of idiopathic short stature. SHOX haploinsufficiency is also associated with various radiographic abnormalities, such as coarse trabecular pattern, short metacarpals/metatarsals with metaphyseal flaring, altered osseous alignment at the wrist, radial/tibial bowing, triangularization of the radial head, abnormal tuberosity of the humerus, and an abnormal femoral neck. Shortening and bowing of the radius and dorsal dislocation of the distal ulna characterize the Madelung deformity. These characteristic findings led us to do a study assessing the predictive value of certain radiographic features in association with genetic markers of idiopathic short stature.


METHODS
Here we describe a case of a Hispanic male with idiopathic short stature and Madelung deformity with a novel mutation in the SHOX gene.


RESULTS
Additional studies revealed a strong family history of short stature and the same SHOX mutation segregating from the mother.


CONCLUSIONS
This case resulted in the description of a novel mutation in exon 5 (M202delA) and suggests the importance of screening for SHOX mutations in patients with idiopathic short stature with subtle radiographic abnormalities, including the components of the Madelung deformity in their bone age films.
Shanske
Alan L
AL
Center for Craniofacial Disorders, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10467, USA. ashanske@montefiore.org
Puri
Mala
M
Marshall
Barbara
B
Saenger
Paul
P
D000293:Adolescent; D001827:Body Height / Q000235:genetics*; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006130:Growth Disorders / Q000188:drug therapy / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010009:Osteochondrodysplasias / Q000235:genetics; D011884:Radius / Q000002:abnormalities; D011994:Recombinant Proteins / Q000627:therapeutic use; D000074122:Short Stature Homeobox Protein; D014457:Ulna / Q000002:abnormalities
D018398:Homeodomain Proteins; D011994:Recombinant Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D019382:Human Growth Hormone