• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Leri-Weill Dyschondrosteosis


Last updated: February 18, 2020
Years published: 1992, 1999, 2002, 2016, 2020


NORD gratefully acknowledges Karen Heath, PhD, Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Spain, for assistance in the preparation of this report.

Disease Overview


Leri-Weill dyschondrosteosis (LWD) is a rare genetic disorder characterized by abnormal shortening of the forearms and lower legs, abnormal misalignment of the wrist (Madelung deformity of the wrist), and associated short stature, which is defined as a child who has a height below percentile 3 (P3) for age, gender and population. Additional symptoms can also occur. The specific symptoms that develop and their severity can vary greatly from one person to another, even among members of the same family. Intelligence is unaffected. LWD is caused by a change (mutation) in the SHOX gene or its regulatory elements (enhancers) located on the pseudoautosomal region 1 (PAR1) of the sex chromosomes (further details described later). It is inherited as a “pseudoautosomal” trait.


Leri-Weill dyschondrosteosis was first described in the medical literature in 1929 by doctors Léri and Weill. The disorder is a skeletal dysplasia and is associated with heterozygous mutations in the short stature homeobox-containing (SHOX) gene or its enhancers. Heterozygous means that an individual carries a single defective gene (i.e. a mutation in one SHOX gene, but not both). Additional disorders in the spectrum include the more severe skeletal dysplasia, Langer mesomelic dysplasia, which arises when there are two SHOX mutations, one on each chromosome (homozygous or compound heterozygous mutations), and in a small proportion (approximately 2.5%) of individuals with idiopathic short stature in which individuals only present with short stature.

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  • Leri-Weill disease
  • Leri-Weill syndrome
  • dyschondrosteosis
  • LWD
  • LWS
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Signs & Symptoms

The specific signs and symptoms associated with LWD can vary greatly from one person to another. Generally, females appear to be affected more severely than males. The classic findings of the disorder are mesomelic shortening of the limbs, short stature, and Madelung deformity. Some individuals do not develop Madelung deformity and/or may obtain normal height.

Mesomelic shortening of the limbs describes abnormal shortening of the middle portion of the arms and legs in relation to the upper (proximal) portions, which means that the forearms and lower legs are disproportionately shorter than the upper arms and legs. Consequently, the arms and legs are disproportionate to the trunk of the body. Sometimes, the shin bone (tibia) and the lower arm (radius and ulna) may be abnormally bowed. Less often, wrist, knee or ankle pain may occur. Mesomelia usually first becomes apparent in school-aged children and can increase in frequency and severity with age. In LWD, the degree of short stature can vary greatly from one person to another. Often, short stature is mild and final adult height is only slightly reduced.

Affected individuals may also have an abnormality of the wrist known as Madelung deformity that becomes more apparent around puberty. Madelung deformity is characterized by the bowing and shortening of the bones in the forearms (the radius and the ulna) and the dislocation of the ulna, resulting in the abnormal deviation or misalignment of the wrist. Generally, bilateral Madelung deformity is observed, i.e. both wrists are affected. Affected individuals may have a limited range of movements of the wrists and elbows and/or may experience wrist pain and visible changes in the appearance of the wrist.

Additional symptoms may include a highly arched roof of the mouth (palate), short, thick middle bones of the hand (metacarpals), abnormal sideways curvature of the spine (scoliosis), and overgrowth (hypertrophy) of the calf muscles.

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In most instances, LWD is caused by alterations (mutations) in or loss (deletion) of the short stature homeobox-containing (SHOX) gene or its regulatory regions. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.

The gene alterations that cause LWD are inherited in an autosomal or pseudoautosomal dominant manner. Pseudoautosomal inheritance is an extremely rare occurrence that involves a gene located both sex chromosomes, the X or Y chromosome.

Genes are found on chromosomes, which are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair that normally consists of an X and Y chromosome for males and two X chromosomes for females. Chromosomes 1 through 22 are known as autosomes; the X and Y chromosomes are known as sex chromosomes.

A gene on an autosome may be passed on to either a male or female child with equal likelihood. This is referred to as autosomal inheritance. However, the sex chromosomes (X and Y) are not passed on equally because a father transmits his X chromosome to his daughters and his Y chromosome to his sons. This is referred to as sex-linked inheritance. A key aspect of sex-linked inheritance is the lack of matched gene pairs between X and Y chromosomes. However, very small areas of the X and Y chromosome have matched genes. During the normal division of reproductive (sex) cells (meiosis), these areas pair up and “crossover”. The genes located in these areas transmit in a fashion similar to genes found on autosomes (pseudoautosomal inheritance). SHOX is one of those genes which is found on the tip of both the X and Y chromosomes.

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Affected populations

LWD is a rare disorder that can affect males or females. More cases of the disorder have been reported in the medical literature in females than in males by a 4:1 ratio. The prevalence is unknown, but often given as between 1 in 1000-2000 in the general population. However, many affected individuals may go misdiagnosed or undiagnosed, making it difficult to determine the true frequency of LWD in the general population.

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A diagnosis is based upon a thorough clinical examination and identification of characteristic physical findings. A diagnosis can be difficult because certain symptoms may not be apparent until puberty. X-ray studies (radiographs), in particular a wrist X-ray, can reveal characteristic changes to the affected bones.

Molecular genetic testing can confirm a diagnosis of LWD in approximately 70% of cases. Molecular genetic testing can detect genetic alterations in SHOX and/or its regulatory elements, known to cause the disorder.

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Standard Therapies

The treatment of LWD is symptomatic and supportive.

Growth hormone therapy may be recommended for children who have not reached puberty in order to improve their childhood and adult height. According to the medical literature, a benefit of 7 to 10 centimeters (approximately 3 to 4 inches) to final height can be achieved. The skeletal defects do not worsen with treatment.

Madelung deformity may not require any therapy or only conservative therapy such as wrist splints or supports, particularly during periods of increased discomfort. The use of ergonomic devices designed to help the wrist may be of benefit. If Madelung deformity causes pain or discomfort, activities that strain the wrist should be limited. Some individuals may have severe Madelung deformity and require orthopedic surgery to alleviate the pain and improve mobility.

Bone growth in individuals with LWD should be monitored regularly by a physician during the growth years.

Genetic counseling is recommended for affected individuals and their families.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For more information about clinical trials conducted in Europe, contact:

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Hisado-Oliva A, Garre-Vázquez AI, Santaolalla-Caballero F, et al. Heterozygous NPR2 Mutations Cause Disproportionate Short Stature, Similar to Léri-Weill Dyschondrosteosis. J Clin Endocrinol Metab. 2015;100(8):E1133-42. http://www.ncbi.nlm.nih.gov/pubmed/26075495

Blum WF, Ross JL, Zimmermann AG, et al. GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial. J Clin Endocrinol Metab. 2013;98(8):E1383-92. https://www.ncbi.nlm.nih.gov/pubmed/%2023720786

Benito-Sanz S, Royo JL, Barroso E, Paumard-Hernández B, Barreda-Bonis AC, Liu P, Gracía R, Lupski JR, Campos-Barros Á, Gómez-Skarmeta JL, Heath KE. Identification of the first recurrent PAR1 deletion in Léri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer. J Med Genet. 2012;49(7):442-50. https://www.ncbi.nlm.nih.gov/pubmed/22791839

Rosilio M, Huber-Lequesne C, Sapin H, et al. Genotypes and phenotypes of children with SHOX deficiency in France. J Clin Endocrinol Metab. 2012;97(7):E1257-65. http://www.ncbi.nlm.nih.gov/pubmed/22518848

Benito-Sanz S, Barroso E, Heine-Suñer D, Hisado-Oliva A, Romanelli V, Rosell J, Aragones A, Caimari M, Argente J, Ross JL, Zinn AR, Gracia R, Lapunzina P, Campos-Barros A, Heath KE.Clinical and molecular evaluation of SHOX/PAR1 duplications in Leri-Weill dyschondrosteosis (LWD) and idiopathic short stature (ISS). J Clin Endocrinol Metab. 2011;96(2):E404-12. https://www.ncbi.nlm.nih.gov/pubmed/21147883

Durand C, Bangs F, Signolet J, Decker E, Tickle C, Rappold G. Enhancer elements upstream of the SHOX gene are active in the developing limb. Eur J Hum Genet. 2010;18(5):527-32. https://www.ncbi.nlm.nih.gov/pubmed/19997128

Blum WF, Crowe BJ, Quigley CA, et al.; SHOX Study Group. Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: Two-year results of a randomized, controlled, multicenter trial. J Clin Endocrinol Metab. 2007;92(1):219-28. https://www.ncbi.nlm.nih.gov/pubmed/17047016

Rappold G, Blum WF, Shavrikova EP, Crowe BJ, Roeth R, Quigley CA, Ross JL, Niesler B.Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency. J Med Genet. 2007;44(5):306-13. https://www.ncbi.nlm.nih.gov/pubmed/17182655

Benito-Sanz S, Thomas NS, Huber C, Gorbenko del Blanco D, Aza-Carmona M, Crolla JA, Maloney V, Rappold G, Argente J, Campos-Barros A, Cormier-Daire V, Heath KE. A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis. Am J Hum Genet. 2005;77(4):533-44. https://www.ncbi.nlm.nih.gov/pubmed/16175500

Munns CP, Glass IA, LaBrom R, et al. Histopathological analysis of Leri-Weill dyschondrosteosis: disordered growth plate. Hand Surg. 2001;6:13-23. http://www.ncbi.nlm.nih.gov/pubmed/11677662

Belin V, Cusin V, Viot G, et al., SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nat Genet. 1998;19:67-69. http://www.ncbi.nlm.nih.gov/pubmed/9590292

Shears DJ, Vassal HJ, Goodman FR, et al. Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis. Nat Genet. 1998;19:70-73. http://www.ncbi.nlm.nih.gov/pubmed/9590293

Binder G, Rappold GA. SHOX Deficiency Disorders. 2005 Dec 12 [Updated 2018 Jun 28]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1215/ Accessed Nov 25, 2019.

Heath K. Leri-Weill Dyschondrosteosis. Orphanet. 2009Available at: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=240 Accessed Nov 25, 2019.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:127300; Last Update: 07/31/2019. Available at: http://omim.org/entry/127300 Accessed Nov 25, 2019.

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