Short stature before puberty: which children should be screened for SHOX deficiency?
OBJECTIVE
We studied the prevalence of deficiency in the short stature homeobox containing gene (SHOX) in prepubertal short-statured children and analyzed the clinical and radiological signs.


METHODS
Screening for SHOX deficiency was performed in 449 prepubertal short-statured children (54% females, aged 4-10 years) by direct sequencing and multiplex ligation probe-dependent amplification. Children with SHOX deficiency were compared to 1:2 age- and gender-matched prepubertal children without SHOX deficiency with respect to left-hand radiographs and anthropometrics including different ratios to height and proposed scores.


RESULTS
We identified 22 (4.9%) patients with SHOX deficiency (64% point mutations). Children with SHOX deficiency demonstrated a mesomelic shortening of extremities. Lower leg lengths but not forearm length was reduced in children <8 years with SHOX deficiency. 36% of all children and none of the children <8 years with SHOX deficiency demonstrated any typical radiologic sign. Increased sitting height-to-height ratio and decreased extremities-to-trunk ratio demonstrated the best positive and negative predictive values to identify SHOX deficiency.


CONCLUSIONS
Screening for SHOX deficiency seems rational, especially in children with increased sitting height-to-height ratio or decreased extremities-to-trunk ratio. These criteria were also valid in young children.
Department of Pediatric Endocrinology, Diabetes and Nutrition Medicine, Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, Datteln, Germany.
Barbara
B
Wolters
Nina
N
Lass
Rainer
R
Wunsch
Beatrix
B
Böckmann
Frank
F
Austrup
Thomas
T
Reinehr
D002648:Child; D002675:Child, Preschool; D005121:Extremities / Q000473:pathology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009929:Organ Size / Q000235:genetics; D017354:Point Mutation; D011627:Puberty; D000074122:Short Stature Homeobox Protein
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein