NORD gratefully acknowledges Professor Michael Briggs, Acting Director, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, for assistance in the preparation of this report.
Metaphyseal chondrodysplasia, Schmid type (MCDS), is a very rare inherited disorder characterized by short stature with abnormally short arms and legs (short-limbed dwarfism) and bowed legs (genu varum). Other physical characteristics may include outward “flaring” of the bones of the lower rib cage, lumbar lordosis, pain in the legs, and/or hip deformities in which the thigh bone is angled toward the center of the body (coxa vara). Such abnormalities of the legs and hips typically result in an unusual “waddling” walk (gait). MCDS is transmitted as an autosomal dominant trait.
In MCDS, portions of the bones of the arms and legs develop abnormally with unusual cartilage formations and subsequent abnormal bone formation at the large end portions (metaphyses) of the long bones. Bone growth normally takes place at the metaphyses, but in individuals with MCDS, the growth plate does not function as well as normal and the bones of the leg bow. Consequently, affected individuals exhibit unusually short arms and legs and short stature (short-limbed dwarfism) that usually become apparent by the second year of life.
Symptoms of MCDS are usually noticed for the first time when an infant begins walking. The legs are bowed (genu varum) and a waddling gait is present. Moderate short stature becomes apparent as the child grows. Affected children may also exhibit a hip deformity in which the thigh bone is angled toward the center of the body (coxa vara), flaring of the bones of the lower rib cage, and/or a small chest (thorax).
Some affected children may experience pain in the legs, pain of the joints (arthritis), and joint stiffness. Joint pain may worsen with age.
MCDS is caused by a mutation of the gene for type X collagen called COL10A1. This gene has been mapped to chromosome 6q21-22.3. MCDS is transmitted as an autosomal dominant trait.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 6q21-22.3” refers to band 21-22.3 on the long arm of chromosome 6. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Metaphyseal chondrodysplasia Schmid type is a very rare bone disorder that affects males and females in equal numbers. Individuals of several large families (kindred) have been documented in the medical literature.
In most cases, the diagnosis of MCDS is suspected during early childhood, usually by the second or third year of life. The diagnosis may be confirmed by a thorough clinical evaluation, identification of characteristic physical findings, and a variety of specialized tests, particularly advanced imaging techniques. These techniques include x-ray studies that may reveal abnormal development of the large (bulbous) ends (metaphyses) of certain bones of the body, particularly those of the arms and legs, abnormal enlargement of the growing end of the upper portion of the thigh bone (capital femoral epiphysis).
Molecular genetic testing for the COL10A1 gene is available to confirm the diagnosis. This test involves sequence of DNA from the COL10A1 gene and should detect any disease causing mutations. Prenatal diagnosis is available if the specific COL10A1 mutation has been identified in the family.
MCDS is often mistaken for vitamin D deficiency rickets. It is important that proper diagnosis is made as to avoid unnecessary and potentially harmful vitamin D therapy.
The treatment of MCDS is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedic surgeons, physical therapists, and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.
Physical therapy and/or orthopedic surgery may help correct certain specific findings associated with metaphyseal chondrodysplasia, Schmid type, such as deformity of the hip.
Early intervention is important to ensure that children with MCDS reach their potential. Special services that may be beneficial to affected children may include speech therapy, special social support, physical therapy, and other medical, social, and/or vocational services.
Growth hormone therapy is not effective to increase final adult height.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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