About dyschondrosteosis

What is dyschondrosteosis?

Dyschondrosteosis is a very rare inherited disorder characterized by unusually shortened, bowed bones in the forearms (radius and ulna), abnormal deviation of the wrist toward the thumb side of the hand due to shortening of the radius and dislocation of the end portion of the ulna (Madelung deformity), unusually short lower legs, and associated short stature (mesomelic dwarfism). Affected individuals may also exhibit abnormalities of the large bone of the upper arm (humerus); abnormal bony growths projecting outward from the surface of the shin bones (exostoses of the tibia); unusually short, broad bones in the fingers and toes; and/or abnormalities of the hipbone (i.e., coxa valga). Dyschondrosteosis appears to affect females more severely than males. The disorder is inherited as an autosomal dominant or "pseudoautosomal" trait.

What are the symptoms for dyschondrosteosis?

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.

What are the causes for dyschondrosteosis?

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.

What are the treatments for dyschondrosteosis?

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.

What are the risk factors for dyschondrosteosis?

Dyschondrosteosis is a genetic disorder that causes abnormal bone growth. It can affect the shape of your bones, including your pelvis and spine. People with this condition may have short stature and have difficulty breathing due to an abnormally shaped chest.

People with dyschondrosteosis typically have short arms and legs, a wide gap between their neck and trunk, an unusually shaped spine, an unusually curved pelvis, and a narrow rib cage. The ribs may be flattened or buckled. People with this condition also tend to have weak muscles that make it difficult for them to walk.

1. Dyschondrosteosis is caused by changes in specific genes involved in bone formation (bone morphogenetic proteins or BMPs).
2. These genes tell cells when it's time to grow new bone tissue and when they should stop growing new bone tissue.
3. In people with dyschondrosteosis, these genes don't work properly so they keep making more bone tissue than normal which leads to abnormal bone growth.
4. In addition, if you have another type of dwarfism, such as pseudoachondroplasia (a form of dwarfism caused by a genetic mutation), then you may be at an even higher risk for developing dyschondrosteosis later in life.

Other risk factors include:

1. Being male
2. Having a family member who has dyschondrosteosis
3. Suffering from any other disease that affects the growth plates, such as osteoporosis or rickets.
4. Having a genetic mutation that affects the growth plates, such as Marfan syndrome or Loeys-Dietz syndrome

Short stature,Dwarfism,Shortening of the long bones in the arms and legs,Unequal length of the arms and legs (asymmetrical growth),Flat feet or excess skin on the back of the neck and upper back (humpback)
Bone deformities,Loss of height,Pain,Inability to walk or stand for long periods of time,Congenital elbow dislocation,Hypermobility of the elbow joint.
Glucocorticoids,Corticosteroid,Vitamin D analogues,Bisphosphonates

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