Short stature before puberty: which children should be screened for SHOX deficiency?

Horm Res Paediatr. 2013;80(4):273-80. doi: 10.1159/000354989. Epub 2013 Sep 18.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Extremities / pathology
  • Female
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / pathology
  • Genetic Diseases, Inborn / physiopathology
  • Growth Disorders / genetics*
  • Growth Disorders / pathology
  • Growth Disorders / physiopathology
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Organ Size / genetics
  • Point Mutation*
  • Puberty*
  • Short Stature Homeobox Protein

Substances

  • Homeodomain Proteins
  • SHOX protein, human
  • Short Stature Homeobox Protein