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.
Presentation
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.
Entire Body System
- Short Stature
FOR Advances in the field of genetics have estimated that about 2% of idiopathic short stature is related to haploinsufficiency of the Short stature homeobox (SHOX) gene, which is found on the short arm of the X and Y chromosomes in the pseudoautosomal [sajr.org.za]
Patients present with short stature because of shortening of the forelegs (tibia/fibula defects) and forearms (with Madelung deformity). There is a higher prevalence in females 4. [radiopaedia.org]
Advances in the field of genetics have estimated that about 2% of idiopathic short stature is related to haplo-insufficiency of the short stature homeobox (SHOX) gene, which is found on the short arm of the X and Y chromosomes in the pseudo-autosomal [go.gale.com]
Keywords: Leri-Weill dyschondrosteosis, Madelung deformity, idiopathic short stature [pediatrics.or.kr]
One of the most common causes of short stature is a defect of the short stature homeobox-containing (SHOX) gene, which is located in pseudoautosomal region 1 on the distal end of the short arm of chromosomes Xp22.33 and Yp11.32. [joms.org]
- Pain
Surgery: Orthopedic surgery is needed for patients having severe Madelung deformity to reduce pain and improve mobility. [epainassist.com]
The typical clinical presentation of Madelung deformity is progressive deformity during late childhood or early adolescence decreased grip strength and wrist pain due to ulnocarpal impaction. [eurorad.org]
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Abnormality of the wrist Abnormality of the wrist, the structure connecting the hand and the forearm. [rarediseases.oscar.ncsu.edu]
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. [rarediseases.org]
Leri Weill Dyschondrosteosis: Image Credit – Hinsdale, Copyright Pr-P-J Weiller In addition, the patient may complain of pain in various joints. [boneandspine.com]
- Fishing
Our case is the youngest patient in literature documented by FISH analysis to have an X to Y chromosome transfer and the first of these patients diagnosed prior to onset of short stature or Madelung deformity. [academiccommons.columbia.edu]
MLPA detected an intragenic deletion involving exons IV-VIa, which was not detected by FISH and microsatellite analysis. [ncbi.nlm.nih.gov]
We report the youngest patient in literature documented by FISH analysis to have an X to Y chromosome transfer of an originally X-located SHOX deletion. [ijpeonline.biomedcentral.com]
- Surgical Procedure
Conclusions Knowledge of this condition has therapeutic implications, given the favourable progress with growth hormone treatment, as well as possible surgical procedures and genetic counselling, due to its autosomal dominant hereditary character. [dialnet.unirioja.es]
procedures 12 Tx of Madelung deformity Splint NSAID Osteotomy of the distal radius ulnar recession E/F with radius osteotomy lengthening Epiphyseodesis Epiphysiolysis with fat interposition Distal radioulnar joint arthrodesis with distal ulnar pseudoarthrosis [powershow.com]
- Falling
Events Top Hyperscale Data Centers & Storage Systems Workshop Date : Tuesday, May 1st, 2018 Venue : DTC Walter Library 402 Spring CRIS Industry Advisory Board Meeting Date : Wednesday and Thursday, May 2 - 3, 2018 Venue : UMN, Minneapolis, MN Fall CRIS [cris.cs.umn.edu]
Makayla got her positive diagnosis right around the same time she started falling off the growth chart (she’s currently hovering around the 2-3 percentile). We’ve recently started seeing Dr. [thriving.childrenshospital.org]
Musculoskeletal
- Coxa Valga
References Growth Adult height 135cm to normal Female preponderance Madelung deformity more frequent and more severe in females Short stature Limbs Abnormality Altered osseous alignment at wrist Bowing of radius Coxa valga Dislocated ulna Dislocation [datagenno.com]
Pelvic bones showed coxa valga and iliac–ischial dysplasia due to defective ossification of the ischial rami (B). [mdpi.com]
valga Genu varum, ankle valgus 14 Leri-Weill dyschondrosteosis SHOX (short stature homeobox-containing gene) SHOX plays a role in chondrocyte function in the growth plate Deletions point mutations lead to haploinsufficiency Autosomal dominant inherited [powershow.com]
- Wrist Pain
pain and decreased grip strength. [eurorad.org]
Wrist pain when lifting object. Forearms shorter with respect to hands and upper arm; distal ulna dorsal dislocation; dislocation easily reduced but unstable. Limited motion of elbows and wrists; legs shorter with respect to thighs. [whonamedit.com]
Patients with Madelung deformity have a limited range of motion of the elbows and wrists and/or can also suffer from wrist pain and changes in the appearance of the wrist. [epainassist.com]
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. [rarediseases.org]
- Severe Short Stature
Both had severe short stature and evidence of rhizomelia and mesomelia as well as other phenotypic features of their individual genetic disorders. [ncbi.nlm.nih.gov]
Individuals with two nonfunctional copies of the SHOX gene have Langer mesomelic dysplasia, a more severe bone dysplasia characterized by severe short stature and an underdevelopment or absence of the ulna and fibula. [crd.york.ac.uk]
Individuals with LMD have problems associated with their severe short stature and severely shortened arms. The documents contained in this web site are presented for information purposes only. [orpha.net]
- Short Forearm
[…] of ulna at wrist elbow or both Distal hypoplasia of the dorsally dislocated ulna leading to a widened gap between radius and ulna Increased carrying angle Limitation of movement Short forearm Show images https://www.datagenno.com/utils/files/images/1098 [datagenno.com]
Abstract In 1929 Léri and Weill (16) described aI case of dwarfism in a young woman with very short forearms and Madelung-like wrist deformities. [pubs.rsna.org]
Physical and auxological examinations revealed mesomelic appearance, ulnarly deviated hands, and borderline micrognathia in the infant, and relatively short forearms and lower legs in the mother. [ncbi.nlm.nih.gov]
forearms and legs (mesomelic dwarfism) and a bayonet-like deformity of the forearms (Madelung's deformity).[1] Causes[edit] It is caused by mutations in the short-stature homeobox gene found in the pseudoautosomal region PAR1 of the X and Y chromosomes [en.wikipedia.org]
Leri Weill dyschondrosteosis is characterized by Variable short stature Short forearms, Tibial/fibular shortening. The height of these patients is usually is less than the 25th percentile. [boneandspine.com]
- Short Extremities
ABSTRACT Background: Léri-Weill dyschondrosteosis, bone dysplasia of genetic origin that affects the mesomelic region with shortening of the extremities, causes short stature with short extremities with Madelung deformity.This disease shows an autosomal [medigraphic.com]
Face, Head & Neck
- 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]
Presence of muscular hypertrophy, cubital valgus, short neck, increased body mass index and decreased arm span height ratio are some further clues to the diagnosis (Rappold et al., 2007). [iamg.in]
[…] of the carpus, being able to find cubitus. valgus, short neck. [mathewsopenaccess.com]
Psychiatrical
- Suggestibility
Want to suggest a symptom? Please send suggestions to RareGuru! [rareguru.com]
[…] involves shortening of the middle segment of the extremities (mesomelia), leading to a moderate degree of dwarfism. 4 Involvement of the lower extremity is common and the presence of body disproportion in an individual with Madelung deformities strongly suggests [appliedradiology.com]
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]
Workup
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].
X-Ray
- X-Ray Abnormal
The association of short stature with typical X ray abnormalities with SHOX deletion suggested the diagnosis of Leri Weill dyschondrosteosis. [iamg.in]
Treatment
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].
Prognosis
Deformities associated with LWD can significantly impact the quality of life of children and the degree of impairment depends on the severity of symptoms.
Etiology
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].
Epidemiology
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].
Pathophysiology
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].
Prevention
Current prevention strategies do not exist, as the exact event that leads to SHOX mutations is yet to be revealed.
Summary
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.
References
- 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.
- 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.
- 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.
- Munns CF, Glass IA, LaBrom R, et al. Histopathological analysis of Leri-Weill dyschondrosteosis: disordered growth plate. Hand Surg. 2001;6(1):13-23.
- 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.
- 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.