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Léri-Weill dyschondrosteosis

Orpha number ORPHA240
Synonym(s) Léri-Weill syndrome
Prevalence Unknown
Inheritance
  • Autosomal dominant
Age of onset Neonatal/infancy
ICD-10
  • Q77.8
OMIM
UMLS
  • C0265309
MeSH
  • C537119
MedDRA -
SNOMED CT
  • 17818006

Summary

Léri-Weill dyschondrosteosis (LWD) is a skeletal dysplasia marked by disproportionate short stature and the characteristic Madelung wrist deformity (see this term).

Prevalence of LWD is unknown.

Short stature is present from birth with mesomelic shortening of the limbs (shortening of the middle segments of the forearms and lower legs). Madelung deformity may only be detected in puberty. The wrist deformity is bilateral and is characterized by shortened and bowed radii and ulnae leading to dorsal dislocation of the distal ulna and limited mobility of the wrist and elbow. Expression is variable but the clinical features are generally more severe in females. Male patients show an athletic body habitus due to muscular hypertrophy, without any underlying muscle disorder. Intelligence is normal.

In around 70 % of cases, LWD is caused by haploinsufficiency of the short stature homeobox (SHOX) gene, which maps to the pseudoautosomal region 1 (PAR1) of the sexual chromosomes (Xp22.33 and Yp11.32). Haploinsufficiency results from heterozygous mutations and deletions of SHOX, or of the downstream PAR1 (where SHOX enhancer elements are located). The molecular defect remains unknown in the remaining 30% of LWD cases. SHOX-associated LWD is part of a spectrum of disorders (ranging from the most severe Langer mesomelic dysplasia (LMD) to LWD, isolated Madelung deformity and so-called idiopathic short stature; see these terms), all associated with SHOX/PAR1 anomalies. The prevalence of SHOX/PAR1 mutations is estimated at 1/1000.

Diagnosis of LWD may be suspected on the basis of the clinical and radiologic findings and can be confirmed by molecular analysis (microsatellite marker analysis, FISH or, preferably, MLPA for PAR1 deletions, HRM, dHPLC and/or DNA sequencing for point mutations, small deletions and insertions of SHOX).

Differential diagnoses should include the other SHOX-related haploinsufficiency disorders and related conditions such as Turner syndrome and distal monosomy Xp (see these terms).

Prenatal testing is available but not common.

LWD is inherited in a pseudoautosomal dominant manner with each child of an affected individual having a 50% chance of inheriting the mutation. If both parents have LWD, the offspring will have a 50% chance of having LWD, a 25% chance of having LMD, and a 25% chance of having neither condition.

Management should include regular surveillance with biannual height evaluations and annual wrist radiographs. Treatment options include administration of recombinant human GH (rhGH) to improve final adult height; or concurrent use of rhGH and gonadotrophin-releasing hormone agonist (GnRHa) to prevent the blunted pubertal growth spurt caused by the presence of estrogen. Molecular genetic testing of at-risk family members ensures early treatment with rhGH therapy to improve growth. Wrist splints, supports and ergonomic devices may reduce wrist discomfort. In some cases, surgical intervention (physiolysis of the ulnar aspect of the distal radius and excision of the Vickers ligament) is required in mid-to-late childhood and may decrease pain and restore wrist function.

Expert reviewer(s)

  • Dr Karen HEATH

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Detailed information

Summary information
Guidance for genetic testing
  • EN (2012,pdf)
Clinical genetics review
  • EN (2008)
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