About jansen type metaphyseal chondrodysplasia

What is jansen type metaphyseal chondrodysplasia?

Jansen type metaphyseal chondrodysplasia is an extremely rare progressive disorder in which portions of the bones of the arms and legs develop abnormally with unusual cartilage formations and subsequent abnormal bone formation at the large (bulbous) end portions (metaphyses) of these long bones (metaphyseal chondrodysplasia). As a result, affected individuals exhibit unusually short arms and legs and short stature (short-limbed dwarfism), findings that typically become apparent during early childhood. Abnormal cartilage and bone development may also affect other bones of the body, particularly those of the hands and feet (i.e., metacarpals and metatarsals). Infants with Jansen type metaphyseal chondrodysplasia may also have characteristic facial abnormalities and additional skeletal malformations. During childhood, affected individuals may begin to exhibit progressive stiffening and swelling of many joints and/or an unusual "waddling gait" and squatting stance. In addition, affected adults may eventually develop abnormally hardened (sclerotic) bones especially in the back of the head (cranial bones), which, in some cases, may lead to blindness and/or deafness. In addition, affected individuals have abnormally high levels of calcium in the blood (hypercalcemia). The range and severity of symptoms may vary from case to case. Most cases of Jansen type metaphyseal chondrodysplasia occur randomly as the result of a spontaneous genetic change (i.e., new genetic mutation).

What are the symptoms for jansen type metaphyseal chondrodysplasia?

In Jansen type metaphyseal chondrodysplasia, an extremely rare progressive disorder, portions of the bones of the arms and legs develop abnormally with unusual cartilage formations and subsequent abnormal bone formation at the large (bulbous) end portions (metaphyses) of these long bones (metaphyseal chondrodysplasia). As a result, affected individuals exhibit unusually Short arms and legs and Short stature (short-limbed dwarfism), findings that typically become apparent during childhood. Abnormal cartilage development and bone formation may also affect other bones of the body, including those of the hands and feet (i.e., metacarpals and metatarsals). As affected individuals age, abnormal cartilage formations in affected areas may harden into rounded (bulbous) masses of bone, which may become prominent.

Most infants with Jansen type metaphyseal chondrodysplasia have characteristic facial abnormalities that are present at birth (congenital) including an unusually Small jaw (micrognathia); receding chin; highly-arched roof of the mouth (palate); unusually wide fibrous joints between bones of the skull (cranial sutures); and/or prominent, widely spaced eyes (ocular hypertelorism).

During childhood, it may become apparent that affected individuals have additional Skeletal abnormalities such as unusually short, clubbed fingers (brachydactyly) with permanent fixation of the fifth finger in a bent position (clinodactyly); an abnormally small lower rib cage; fractured ribs; and/or malformations of the spine and pelvis. As affected children age, they may eventually develop abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis) and/or bowing of the legs. In addition, Short stature becomes more obvious as affected children age; the torso grows longer, but the arms and legs do not grow proportionally.

Children with Jansen type metaphyseal chondrodysplasia may also experience diminished muscle mass and gradual Swelling of certain joints, particularly the hips and knees. Affected joints may become stiff and painful and certain movements, particularly bending (flexion), may become limited. Most affected children develop an unusual semi-squatting stance and a “waddling” walk (gait). Eventually, certain joints may become fixed in a permanently bent (flexed) position (joint contractures).

Intellectual disability and a delay in the acquisition of skills requiring coordination of muscular and mental activity (psychomotor retardation) have not been reported in patients with Jansen metaphyseal chondrodysplasia.

Some adults with Jansen type metaphyseal chondrodysplasia may eventually exhibit overgrowth of the bones above the eyes and those of the forehead (supraorbital and frontonasal hyperplasia), an unusually thickened base of the skull, and/or abnormal hardening (sclerosis) of certain cranial bones. In some patients, sclerosis of certain cranial bones may eventually result in Blindness and/or deafness. Affected adults may also exhibit additional joint contractures. In addition, affected individuals have abnormally high levels of calcium in the blood (hypercalcemia). The degree of hypercalcemia may vary in different patients. At least one mild form of Jansen type metaphyseal chondrodysplasia has been identified in which affected family members had less-pronounced skeletal abnormalities.

What are the causes for jansen type metaphyseal chondrodysplasia?

The gene that is probably involved in most cases of Jansen type metaphyseal chondrodysplasia associated with hypercalcemia is located on the short arm (p) of chromosome 3 (3p21.1-p22). Chromosomes 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 of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” In order for researchers to clearly refer to the thousands of genes that may be present on one chromosome, both the long arm and short arm of each chromosome are divided into many bands that are numbered.

Jansen type metaphyseal chondrodysplasia is caused by a change (mutation) in a gene that encodes for a specific protein (i.e., PTH/PTHrP receptor). Parathyroid hormone helps to regulate the levels of calcium in the blood.

Most cases of Jansen type metaphyseal chondrodysplasia occur randomly as the result of a spontaneous genetic change (i.e., new mutation). Inheritance is autosomal dominant. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

What are the treatments for jansen type metaphyseal chondrodysplasia?

The treatment of Jansen type metaphyseal chondrodysplasia 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, dental specialists, speech pathologists, specialists who assess and treat hearing problems (audiologists), 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 Jansen type metaphyseal chondrodysplasia, such as deformities of the joints.

Early intervention is important to ensure that children with Jansen type metaphyseal chondrodysplasia reach their highest 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.

Genetic counseling is recommended for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.

What are the risk factors for jansen type metaphyseal chondrodysplasia?

Jansen-type metaphyseal chondrodysplasia is a rare disorder of the bones that results in dwarfism, shortening and thickening of the limbs, and abnormal curvature of the spine. It is caused by mutations in a gene, which encodes dysferlin—a protein that plays an important role in cartilage formation.

The disease is characterized by delayed skeletal growth with short stature, shortening of the lower extremities relative to the upper extremities (known as "trident" deformity), pain in bones and joints, progressive spinal curvature due to vertebral malformation, and bowing of long bones.

The cause of JMCD is unknown. It appears to be inherited in an autosomal dominant manner, which means that having one changed gene from one parent is enough to cause the disorder. In some cases, two parents with the same mutation can have a child with JMCD.

The risk factors for Jansen-type metaphyseal chondrodysplasia include:

1. A family history of the disease or other conditions that affect bone growth, such as osteogenesis imperfecta and osteopetrosis.

2. Aging parents. While this is not a direct cause, it can increase the risk of passing on an abnormal gene to your child.

3. Exposure to radiation during pregnancy or in early childhood (this can cause mutations in certain genes).

4. Being born prematurely or small for gestational age

5. Having a low birth weight

Symptoms
Pain in the lower back or sacroiliac area,Pain on one side of the body,A limp when walking,Joints that are abnormally loose (hypermobility) or stiff (hypomobility)
Conditions
The joints, especially the knees and ankles, are often affected. The joint pain may be severe, but joint damage is rare,The bones will also feel brittle and weak, and will sometimes break easily,There may be muscle weakness in the legs and arms,Other symptoms include: short stature; short fingers or toes; high forehead; small jawbones; and large ears
Drugs
Dexamethasone,Prednisone,NSAIDs (Non-steroidal anti-inflammatory drugs),Corticosteroid injections,Bisphosphonates

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