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Léri-Weill dyschondrosteosis (SHOX deficiency)

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A 10-year-old girl with short stature has mesomelic limb shortening (forearms and lower legs) and a visible wrist deformity (Madelung deformity).

Pseudoautosomal dominant; SHOX gene (PAR1 region)

  • Haploinsufficiency
  • Also contributes to short stature in Turner syndrome
  • Mesomelic short stature (middle segments shortened)
  • Madelung deformity (dorsal bowing of radius, triangular carpals)
  • More severe in females
  • Homozygous variants → Langer mesomelic dysplasia (more severe)
  • Clinical: disproportionate mesomelic short stature with Madelung deformity, often more pronounced in females
  • Radiographs of the wrist: dorsal bowing of the radius, triangularized distal radial epiphysis, and pyramidal/triangular carpal arrangement (Madelung deformity)
  • SHOX deletion/duplication analysis (most cases are deletions of SHOX or its enhancers) plus sequencing confirms
  • Consider in girls evaluated for short stature; exclude Turner syndrome with a karyotype when clinically indicated
  • Growth hormone therapy can improve height outcomes in SHOX deficiency
  • Orthopedic referral for symptomatic Madelung deformity; surgical correction (for example, dome osteotomy) for pain or functional limitation
  • Monitor growth and skeletal proportions through childhood and adolescence

The SHOX gene is located in pseudoautosomal region 1 (PAR1) and is found on both the X and Y chromosomes. SHOX haploinsufficiency contributes to short stature in both LWD and Turner syndrome.

SHOX gene location in pseudoautosomal region 1 (PAR1) on both X and Y chromosomes, with PAR2 shown for comparison
SHOX gene location in pseudoautosomal region 1 (PAR1) on both X and Y chromosomes, with PAR2 shown for comparison

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