What Is Jansen Metaphyseal Chondrodysplasia?
Jansen-type metaphyseal chondrodysplasia is a sporadic progressive disorder characterized by abnormal development of the portions of the arms and legs with unusual cartilage formations, which subsequently leads to abnormal bone formation at the bulbous end portions (metaphyses) of these long bones (metaphyseal chondrodysplasia). As a result, the individuals affected with this condition have unusually short arms and legs and are shortly built (short-limbed dwarfism), which typically becomes apparent during early childhood. Abnormal cartilage and bone development may also affect other body bones, particularly the hands, and feet. Infants with this condition may also exhibit characteristic facial abnormalities and additional skeletal defects. In addition, there might be the eventual development of abnormally hardened (sclerotic) bones in adults, particularly at the back of the head (cranial bones), which, in some cases, may cause blindness and/or deafness. They might also have abnormally high calcium levels in the blood (hypercalcemia). The range and seriousness of symptoms may vary from person to person. Most cases of Jansen-type metaphyseal chondrodysplasia occur randomly due to a spontaneous change in a gene (a new genetic mutation).
What Are the Signs and Symptoms of Jansen Metaphyseal Chondrodysplasia?
Since this is a progressive disorder, with the increased age of the affected individuals, abnormal cartilage formations in affected areas may stiffen into large rounded (bulbous) masses of bone, which may get prominent.
Symptoms of characteristic facial abnormalities seen in most infants with Jansen-type metaphyseal chondrodysplasia that are present at birth (congenital) include the following:
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A tiny jaw (micrognathia).
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Receding chin.
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High-arched palate.
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Extensive fibrous joints between skull bones (cranial sutures).
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Prominent, wide-spaced eyes (ocular hypertelorism).
Some additional skeletal abnormalities that may become apparent during childhood include the following:
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Unusually short, clubbed fingers (brachydactyly) with permanent fixation of the little (pinky) finger in a bent position (clinodactyly).
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An abnormally tiny lower rib cage.
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Fractured ribs.
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Spine and pelvic malformations.
As affected children age, they may eventually develop the following symptoms-
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Abnormal front-to-back and side-to-side spine curvature (kyphoscoliosis).
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Bowing of the legs.
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Short stature is more evident.
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Longer torso.
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Disproportionate arms and legs.
Children with Jansen-type metaphyseal chondrodysplasia may also have reduced muscle mass and progressive swelling of certain joints, especially the knees and hips. Affected joints may stiffen and become painful, leading to certain limited movements, particularly bending (flexion). Most affected children develop an unusual “waddling” walk (gait) and a semi-squatting stance. Eventually, certain joints may get permanently fixed in a bent position (joint contractures).
Some adults with this condition may eventually exhibit bony overgrowth above the eyes and forehead (supraorbital and frontonasal hyperplasia), an unusual thickening at the skull base, and abnormal hardening (sclerosis) of certain cranial bones. This sclerosis may eventually lead to blindness and/or deafness in some patients. Affected adults may also show other joint contractures. In addition, affected individuals have abnormally elevated calcium levels in the blood (hypercalcemia). The degree of hypercalcemia may vary.
What Causes Jansen Metaphyseal Chondrodysplasia?
The gene involved in most cases of Jansen metaphyseal chondrodysplasia is most probably located on the short arm (p) of chromosome 3 (3p21.1-p22). Chromosomes carry each individual's genetic information and are found in the cell's nucleus. Human chromosome pairs are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm, “p,” and a long arm, “q.” Jansen metaphyseal chondrodysplasia is caused by an alteration (mutation) in a gene that encodes for a specific protein. Most cases occur randomly due to a spontaneous gene mutation.
Inheritance is autosomal dominant, meaning a single copy of an abnormal gene from either parent is required to cause a particular disease or can result from a mutated gene in the affected individual. The risk of passing the abnormal gene is 50 percent for each pregnancy. The risk is equal for males and females.
How Is Jansen Metaphyseal Chondrodysplasia Diagnosed?
The diagnosis of Jansen-type metaphyseal chondrodysplasia may be detected during infancy or early childhood. A thorough clinical evaluation may confirm the diagnosis, identification of characteristic physical findings, and various specialized tests, particularly advanced imaging techniques. These techniques involve X-ray studies that may show abnormal development of the prominent (bulbous) ends (metaphyses) of certain bones of the body, particularly those of the arms and legs. In addition, laboratory tests that detect abnormal elevation of calcium levels in the urine (hypercalciuria) and blood (hypercalcemia) help confirm the diagnosis.
How Is Jansen Metaphyseal Chondrodysplasia Treated?
The treatment of Jansen-type metaphyseal chondrodysplasia is directed to manage specific symptoms. Therefore, treatment may require the coordinated efforts of a team of specialists. Orthopedic surgeons, dental specialists, pediatricians, speech pathologists, physical therapists, specialists who assess and treat hearing problems (audiologists), and other health care professionals may need to comprehensively and systematically plan a child’s treatment.
Physical therapy or orthopedic surgery may help to correct specific symptoms such as deformities of the joints.
Early intervention is essential to ensure that children affected with Jansen-type metaphyseal chondrodysplasia reach their highest potential. Special services that may benefit include speech therapy, exceptional social support, physical therapy, and other medical and vocational services.
Genetic counseling is also recommended. Researchers are studying the use of bisphosphonates to treat individuals with Jansen-type metaphyseal chondrodysplasia. Extensive research is required to determine bisphosphonates' long-term safety and effectiveness as a potential treatment option for this disorder.
Conclusion:
Jansen metaphyseal chondrodysplasia is an extremely rare disorder that causes severe skeletal abnormalities in children and adults. It is an inherited disorder and holds equal risk for both males and females. A team of specialists from various specialties is required for effective and comprehensive treatment, especially for children.
