Information on the following diseases can be found in the Related Disorders section of this report:

• McKusick Type Metaphyseal Chondrodysplasia (Cartilage-Hair Hypoplasia)
• Jansen Type Metaphyseal Chondrodysplasia
• Spahr Type Metaphyseal Chondrodysplasia
• Vitamin-D Deficiency Rickets
• .

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 shuts down prematurely 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).

In some cases, 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 COL XA1. 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.

Schmid Type Metaphyseal Chondrodysplasia 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.
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Symptoms of the following disorders can be similar to those of Schmid Type Metaphyseal Chondrodysplasia. Comparisons may be useful for differential diagnosis:

McKusick Type Metaphyseal Chondrodysplasia, also known as Cartilage-Hair Hypoplasia, is an extremely rare inherited disorder characterized by unusually fine, sparse hair and abnormal development of the cartilage and subsequent bone formation in the long bones of the arms and legs (metaphyseal chondrodysplasia), resulting in unusually short arms and legs and short stature (short-limbed dwarfism). Most affected individuals exhibit impairment of certain white blood cells (T-cells) that play an important role in helping the body's immune system fight certain infections (cellular immunodeficiency). In addition, affected individuals may also exhibit impaired absorption of certain necessary nutrients (malabsorption); abnormally low levels of certain white blood cells in the body (neutropenia and lymphocytopenia); low levels of circulating red blood cells (anemia); increased susceptibility to repeated infections, such as chickenpox; abnormalities of the teeth; and/or other physical findings. The range and severity of symptoms vary widely from case to case. McKusick Type Metaphyseal Chondrodysplasia is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "McKusick Type Metaphyseal Chondrodysplasia" as your search term in the Rare Disease Database.)

Jansen Type Metaphyseal Chondrodysplasia is an extremely rare inherited disorder characterized by severe short stature with abnormally short arms and legs (short-limbed dwarfism). Abnormally short arms and legs result from the improper formation of the cartilage at the end portions (metaphyses) of the long bones (metaphyseal chondrodysplasia). Improper cartilage development may also occur in the metaphyses of other bones of the body, particularly those of the hands and feet (i.e., metacarpals and metatarsals). Affected children may also exhibit malformation of certain bones of the skull; deformities of certain joints including swelling, pain, and stiffness; abnormally short fingers (brachydactyly); and/or abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis). In addition, affected children may have abnormally high levels of calcium in the blood (hypercalcemia). Jansen Type Metaphyseal Chondrodysplasia is thought to be inherited as an autosomal dominant genetic trait. (For more information on this disorder choose, "Jansen Type Metaphyseal Chondrodysplasia " as your search term in the Rare Disease Database.)

Spahr Type Metaphyseal Chondrodysplasia is an extremely rare inherited disorder characterized by abnormal development of the cartilage and subsequent bone formation in the long bones of the arms and legs (metaphyseal chondrodysplasia), resulting in severely bowed legs and short stature (short-limbed dwarfism). This disorder is very similar to Schmid Type Metaphyseal Chondrodysplasia except Spahr Type Metaphyseal Chondrodysplasia is thought to be inherited as an autosomal recessive genetic trait.

Vitamin D Deficiency Rickets is a rare inherited disorder characterized by skeletal abnormalities due, in most cases, to a deficiency in vitamin D levels (Type I) or inability to properly utilize vitamin D (Type II). Skeletal abnormalities may include bowed legs; abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis); malformations of the bones of the spine, pelvis, and legs; and/or, in severe cases, abnormal side-to-side (horizontal) depression of the lower portion of the chest cavity (Harrison Groove). In most cases, affected infants will exhibit abnormally low levels of calcium in the blood (hypocalcemia). (For more information on this disorder, choose "Rickets, Vitamin D Deficiency" as your search term in the Rare Disease Database.)
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Diagnosis
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 COL XA1 gene is available to confirm the diagnosis. Prenatal diagnosis is available if the specific COL XA1 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.

Treatment
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.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Savariarayan R. Schmid Metaphyseal Chondrodysplasia. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:248.

McKusick VA, ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Metaphyseal Chondrodysplasia, Schmid Type; MCDS. Entry Number; 156500: Last Edit Date; 9/11/1998.

McKusick VA, ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Collagen, Type X, Alpha-1; COL10A1. Entry Number; 120110: Last Edit Date; 11/18/2002.

TEXTBOOKS
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Jones KL. ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:382-86.

Royce PM, Steinmann B. Connective Tissue and Its Heritable Disorders. 2nd ed. Wiley-Liss, Inc., New York, NY. 2002:919-20.

REVIEW ARTICLE
Olsen BR. Mutations in collagen genes resulting in metaphyseal and epiphyseal dysplasias. Bone. 1995;17(2 Suppl):45S-49S.

JOURNAL ARTICLES
Kanazawa H, Tanaka H, Inoue M, et al. Efficacy of growth hormone therapy for patients with skeletal dysplasia. J Bone Miner Metab. 2003;21:307-10.

Nishimura G, Manabe N, Kosaki K, et al. Spondylar dysplasia in type X collagenopathy. Pediatr Radiol. 2001;31:76-80.

Savarirayan R, Cormier-Daire V, Lachman RS, et al. Schmid type metaphyseal chondrodysplasia: a spondylometaphyseal dysplasia identical to the “Japanese” type. Pediatr Radiol. 2000;30:460-63.

Matsui Y, Yasui N, Kawabata H, et al. A novel type X collagen gene mutation (G595R) associate with Schmid-type metaphyseal chondrodysplasia. J Hum Genet. 2000;45:105-08.

Ikegawa S, Nishimura G, Nagai T, et al. Mutation of the type X collagen gene (COL10A1) causes spondylometaphyseal dysplasia. Am J Hum Genet. 1998;63:1659-62.

FROM THE INTERNET
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www.biomed.man.ac.uk/staff/user.asp?id=382&item=Research

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Metaphyseal chondrodysplasia. Amersham Health. nd. 1pp.
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Metaphyseal chondrodysplasia, type schmid. Amersham Health. nd. 2pp.
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What is cartilage? Polychondritis Educational Society, Ltd. Last updated on: March 26, 2004.
www.polychondritis.com/WhatisCartilage.html

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