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Leri-Weill Dyschondrosteosis


Leri-Weill dyschondrosteosis is a rare genetic disease that induces short stature and limb abnormalities primarily due to to SHOX gene mutations. The diagnosis can be made by observing typical clinical findings and identification of specific genetic mutations. Growth hormone therapy may be an option, but there is no cure for this disorder and long-term symptomatic care is necessary.


The clinical presentation includes a triad of symptoms [1] [2] [5]:

  • Short stature - Growth failure and reduced height in early childhood is an essential feature of LWD.
  • Madelung deformity - Defined as deformity of the wrist and abnormal placement of radius and ulna, this anatomical malformation is most evident in later childhood and can cause significant movement restriction, limiting supination and pronation.
  • Mesomelia - Disproportionately shorter segments of the middle limb portion induces overall shortening of the extremities, leading to evidently abnormal limb anatomy.
  • MLPA detected an intragenic deletion involving exons IV-VIa, which was not detected by FISH and microsatellite analysis.[ncbi.nlm.nih.gov]
  • FISH analysis with specific probes for SHOX and SRY displayed no signal on the der(X), while one signal for SHOX was detected on the normal X chromosome in the mother, and one signal each for SHOX and SRY was detected on the normal Y chromosome in the[ncbi.nlm.nih.gov]
  • FISH analysis with SHOX and SRY gene probes was carried out. One copy of both SHOX and SRY was detected in interphase nuclei, clarifying the origin of LWD and the male phenotype.[ncbi.nlm.nih.gov]
  • METHODS: SHOX gene deletion was evaluated by fluorescence in situ hybridization (FISH), Southern blotting and segregation study of polymorphic marker. Point mutations were assessed by direct DNA sequencing.[ncbi.nlm.nih.gov]
  • We performed multiple ligation probe amplification (MLPA) assay in six Japanese LWD patients with apparently normal SHOX, followed by fluorescent in situ hybridization (FISH) analysis and sequencing for polymerase chain reaction (PCR) products encompassing[ncbi.nlm.nih.gov]
Short Disproportionate Stature
  • Methods and Results: We report a unique case of an 8-year-old girl who was successfully treated for acute lymphoblastic leukemia (pre-B ALL, intermediate risk) and was subsequently diagnosed with LWS due to characteristic clinical appearance (short disproportionate[biomed.papers.upol.cz]
High Arched Palate
  • In comparing the LWD and TS populations in the GeNeSIS sample, Madelung deformity, increased carrying angle, and scoliosis were more prevalent in the LWD population, whereas high arched palate was similarly prevalent in the two populations.[ncbi.nlm.nih.gov]
  • His mother had LWD plus additional findings of Turner syndrome (TS): high arched palate, bicuspid aortic valve, aortic stenosis, and premature ovarian failure. The proband's karyotype was 46,X,dic(X;Y)(p22.3;p11.32).[ncbi.nlm.nih.gov]
  • Other features of Leri Weill dyschondrosteosis can include increased muscle size, elbow abnormalities, scoliosis , high-arched palate, and exostoses . Intelligence is not affected by this condition.[globalgenes.org]
  • Short stature Shortening of lower limbs Abnormality of wrist Sometimes underdevelopment of jaw Increased muscle mass Bowing of lower leg Greater angling of elbow from body High arched palate *Please be aware, not all of the characteristics may be present[littlepeopleuk.org]
  • Other features of Leri Weill dyschondrosteosis can include increased muscle size, elbow abnormalities, scoliosis, high-arched palate, and exostoses. Intelligence is not affected by this condition.[resourcerepository.org]
  • This suggests either genetic heterogeneity or the presence of mutations in unanalyzed regions of SHOX, such as the upstream, intragenic, or downstream regulatory sequences.[ncbi.nlm.nih.gov]
  • The phenotypes of combined LWD and achondroplasia or hypochondroplasia appeared to be less than additive, suggesting that SHOX and FGFR3 act on overlapping pathways of bone growth and development. Copyright 2002 Wiley-Liss, Inc.[ncbi.nlm.nih.gov]
  • The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC).[ncbi.nlm.nih.gov]
  • The results, in conjunction with those reported by Flanagan et al. [2002], suggest that a cis-acting enhancer exists in the SHOX 3' region around DXYS233.[ncbi.nlm.nih.gov]
  • Molecular results suggested that the 45,X karyotype arose through two independent events. The first occurred at paternal meiosis leading to an unequal crossing over between the short arms of the X and Y chromosomes.[ncbi.nlm.nih.gov]
Short Neck
  • The physical examination showed dysmorphic aspect with shortening of arms and legs, small hands and feet, and short neck. Hypertension was not confirmed.[revistaseletronicas.pucrs.br]


A presumptive diagnosis can be made based on clinical findings during physical examination, but X-rays of the affected extremities can support clinical suspicion. Decreased length of ulna and radius, early fusion of the ulnar half of the distal epiphysis and dorsal subluxaton of the ulna are some of the most common radiological findings [1]. To confirm LWD, however, genetic testing for SHOX gene mutations should be performed [2].


Recombinant human growth hormone (rhGH) can be used in the attempt to promote growth, although symptomatic care of patients is the main form of therapy, as there is no cure for LWD [1] [6].


Deformities associated with LWD can significantly impact the quality of life of children and the degree of impairment depends on the severity of symptoms.


Mutations and deletions of one copy of the SHOX gene from the short arms of either X or Y chromosomes is presumed to be the underlying mechanism of LWD development [4] [5]. The disorder is transferred through a pseudoautosomal dominant pattern of inheritance, but in 40% of cases, SHOX mutations have not been confirmed and the underlying cause remains unknown [5].


Incidence and prevalence rates of LWD are unknown. Numerous reports have addressed its more frequent occurrence females, as well as its more severe clinical presentation, possibly due to the effects of estrogen on skeletal tissue [2] [5].

Sex distribution
Age distribution


Alterations in SHOX genes have shown to be important constituents of many conditions that result in short stature, including LWD. The pathogenesis model is still not completely understood, but normal chondrocyte differentiation and maturation is shown to be impaired, leading to premature fusion of the physis and earlier cessation of longitudinal bone growth [1].


Current prevention strategies do not exist, as the exact event that leads to SHOX mutations is yet to be revealed.


Leri-Weill dyschondrosteosis (LWD) is a pseudoautosomal dominant genetic disease that presents with a clinical triad of short stature, mesomelia (shortening of the middle portion of the limb in relation to the proximal portion) and abnormal anatomy of the radius, ulna and the carpal bones, known as Madelung deformity [1]. Mutations in the short stature homeobox containing gene (SHOX) located on X and Y chromosomes is thought to be the underlying cause [2], but in up to 40% of cases, SHOX mutations are not encountered and the etiology remains unknown [3]. LWD is considered to be a rare disease with unknown incidence and prevalence rates and symptoms become evident in school-aged children [1]. The diagnosis can be made based on clinical findings that are supported by radiographic and genetic studies [2]. Recombinant human growth hormone (rhGH) may be used to promote growth [2].

Patient Information

Leri-Weill dyschondrosteosis (LWD) is a rare genetic disease that causes short stature and limb abnormalities. In about 60% of cases, the disorder stems from mutations of short stature homeobox containing gene (SHOX) located on chromosomes X and Y (known as sex chromosomes). LWD is transmitted by an autosomal dominant pattern of inheritance, meaning that children have a 50% of contracting the disease if one parent carries a mutation. A triad of shot stature, reduced limb length (mesomelia) and displacement of bones in the forearm (Madelung deformity) appearing in school-aged children (more commonly female) is the hallmark of LWD and the initial diagnosis can be made based on identifying these findings. To confirm this rare inherited condition, however, genetic testing is necessary. Current therapy includes administration of recombinant human growth hormone to stimulate growth and symptomatic care, as LWD may have an impact on the quality of life in terms of limited mobility of the affected extremities and basic daily functions.



  1. Binder G, Rappold GA. SHOX Deficiency Disorders. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
  2. Choi WB, Seo SH, Yoo WH, Kim SY, Kwak MJ. A Leri-Weill dyschondrosteosis patient confirmed by mutation analysis of SHOX gene. Ann Pediatr Endocrinol Metab. 2015;20(3):162-165.
  3. Benito-Sanz S, Thomas NS, Huber C, et al. A Novel Class of Pseudoautosomal Region 1 Deletions Downstream of SHOX Is Associated with Léri-Weill Dyschondrosteosis. Am J Hum Genet. 2005;77(4):533-544.
  4. Munns CF, Glass IA, LaBrom R, et al. Histopathological analysis of Leri-Weill dyschondrosteosis: disordered growth plate. Hand Surg. 2001;6(1):13-23.
  5. Binder G, Renz A, Martinez A, et al. SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity. J Clin Endocrinol Metab. 2004;89(9):4403-4408.
  6. Salmon-Musial AS, Rosilio M, David M, et al. Clinical and radiological characteristics of 22 children with SHOX anomalies and familial short stature suggestive of Léri-Weill Dyschondrosteosis. Horm Res Paediatr. 2011;76(3):178-85.

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Last updated: 2019-07-11 20:18