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   :
- 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
Despite having almost the same genetic constitution as 47,XXY Klinefelter syndrome, he was normally virilized, although slight elevation of serum gonadotropins indicated gonadal dysfunction. [ncbi.nlm.nih.gov]
Proportionate Short Stature
SHOX Specificity 100 % Genes 100 % Proportionate Short Stature/Small for Gestational Age: Sequencing and Deletion/Duplication Panel. By EGL Genetic Diagnostics Eurofins Clinical Diagnostics in United States. [mendelian.co]
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 . To confirm LWD, however, genetic testing for SHOX gene mutations should be performed .
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  .
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  . 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 .
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  .
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 .
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 . Mutations in the short stature homeobox containing gene (SHOX) located on X and Y chromosomes is thought to be the underlying cause , but in up to 40% of cases, SHOX mutations are not encountered and the etiology remains unknown . LWD is considered to be a rare disease with unknown incidence and prevalence rates and symptoms become evident in school-aged children . The diagnosis can be made based on clinical findings that are supported by radiographic and genetic studies . Recombinant human growth hormone (rhGH) may be used to promote growth .
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.
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