TRPS2

Related Terms

Autosomal dominant disorder, continuous gene deletion syndrome, exostoses, hereditary multiple exostoses type 1, Langer-Giedion syndrome, tricho-rhino-phalangeal syndrome type 1, trichorhinophalangeal syndrome, trichorhinophalangeal syndrome type II, TRPS2.

Background

Langer-Giedion syndrome (LGS) is a very rare genetic disorder that is characterized by distinct facial features and bone abnormalities, including thinly-growing hair, large nose and ears, and malformed fingers and toes.
LGS is caused by mutation, or damage, to genes along one section of one of the cell's chromosomes, which are the structures within each cell that control how that cell develops. The mutation that causes LGS removes a section of chromosome 8 that contains two genes, EXT1 and TRPS1.
The EXT1 gene provides the instructions for making a protein that is needed to form new blood vessels. Mutations in this gene cause a disease called hereditary multiple exostoses type 1. This disease is characterized by the growth of exostoses, which are bony growths on the ends of some bones, including those in the arms, legs, hips, and spine.
Mutations in TRPS1 cause a condition called tricho-rhino-phalangeal syndrome type 1, which is characterized by abnormal facial and head features, including sparse hair, ears that stick out, a large and round nose, and flat upper lip. People missing this gene also develop cone-shaped tips on the ends of some bones, commonly those in the hands and feet.
LGS is also called trichorhinophalangeal syndrome type II. This name refers to features that are affected by this syndrome: the hair (tricho), nose (rhino), and the fingers and toes (phalangeal).
There is currently no cure for Langer-Giedion syndrome. Treatment helps manage the symptoms, which are not life-threatening but can adversely affect the patient's quality of life.

Signs and symptoms

Facial features: A set of facial and bone symptoms are characteristic of Langer-Giedion syndrome (LGS). The most common deformities that affect the face and skull include sparse hair, large ears that stick out, a large and round nose, a missing indentation in the upper lip, and broad eyebrows.
Bone abnormalities: Bone deformities may include bony growths along the ends of bones (called exostoses) and abnormal, cone-shaped ends of certain bones, often in the hands and feet.
Exostoses become apparent during the first few years of life and increase in both number and size as the child grows. These abnormal growths may cause pain and interfere with a person's ability to bend at the joints. In some cases, exostoses may interfere with bone growth to the point that the bone does not reach normal adult length.
Other: Symptoms that may also be present include delayed mental development, smaller than normal-sized head, short stature, overly flexible joints, excessive skin folds (called "redundant" skin), hearing loss, poor muscle tone, and delayed speech development.

Diagnosis

Langer-Giedion syndrome (LGS) is usually diagnosed based on the patient's characteristic signs and symptoms. As with other genetic disorders, a blood test, performed at a laboratory that does genetic testing, can confirm the diagnosis.
Follow-up X-rays, CT scans, or magnetic resonance imaging (MRI) scans evaluate the presence and extent of bone abnormalities. This is important because, while bumps on bones near the surface are easily seen, periodic tests are needed to keep track of growths on interior bones.
The patient's physician will also note any problems that result from disrupted bone growth, including short stature, bowed arms or legs, or lack of normal movement in joints.
Additional testing may be needed to check for speech and/or hearing impairments, as well as possible mental development delays.

Complications

Arthritis: Pain and stiffness in affected elbows and ankles are common as patients get older, and early arthritis is a potential complication of the disorder.
Cancer: The risk of exostoses becoming cancerous is small. Potential warning signs, such as a marked increase in the size of an exostosis in an adult or increased pain from an exostosis in a child, both warrant a closer look. X-rays, CT scans, and MRIs may be used to periodically assess exostoses that are not visible on bone surfaces near the skin. However, it is not yet clear if the benefit of this form of surveillance outweighs the potential risks of exposure to irradiation. It is also not known how often this screening should occur.
Learning disabilities: Children with Langer-Giedion syndrome (LGS) commonly show mild to moderate delays in mental development.
Mobility and discomfort: Depending on their location, exostoses may interfere with normal movement, irritate the surrounding tissue, or pinch nearby nerves. In these cases, patients may opt for surgery to remove bony growths.

Treatment

General: There is currently no cure for Langer-Giedion syndrome (LGS). Instead, treatment focuses on providing relief of symptoms as well as support to the patient and family.
Cosmetic surgery: Cosmetic surgeries may be considered to correct some of the deformities affecting the face and head. Some options include otoplasty, which sets prominent ears closer to the head; rhinoplasty, which is done to improve the size and appearance of the nose; and blepharoplasty, which tightens droopy eyelids.
Orthopedic surgery: Orthopedic (bone) surgery may be an option in cases in which the growth of exostoses is causing pain or limiting mobility. It might also be considered to relieve the stress caused by the protruding growths on the skin and underlying tendons and nerves. Additionally, doctors may propose surgery if the presence of exostoses is causing the bones in one arm or leg to grow faster than the other or if the disorder is interfering with the ability of the hip bones to adequately balance body weight.
Physical therapy: Physical therapy may be needed to increase or maintain flexibility of affected limbs. The goal of physical therapy is to improve mobility, restore function, reduce pain, and prevent further injury by using a variety of methods, including exercises, stretches, traction, electrical stimulation, and massage.
Counseling: In addition, the patient and family may benefit from psychological counseling to deal with the life-long implications of this disorder.
Other therapies: Other services that may be required include evaluation and treatment of speech or hearing impairments and early childhood intervention programs to address developmental delays.

Integrative therapies

Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Langer-Giedion syndrome.

Prevention

There is currently no known way to prevent Langer-Giedion syndrome (LGS). If a person has a family history of LGS, genetic testing may be performed to determine if he/she carries the mutated gene. Parents who have LGS have a 50% chance of passing the disorder to their children.
Genetic testing commonly uses a blood sample or buccal smear (from cells inside the cheek) to look for changes in certain chromosomes, genes, or proteins. Prenatal genetic testing requires a sample of amniotic fluid, which is found in the sac that surrounds and protects a developing fetus. The benefit of testing should be weighed against the potential risk of complications, such as miscarriage, that may result from the procedure.
Before and after genetic testing, it is recommended that people meet with genetic counselors. A genetic counselor can explain the different types of genetic tests, including their potential risks and benefits. These counselors can help patients understand and interpret genetic test results.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

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Causes

General: Langer-Giedion syndrome (LGS) is a genetic disorder, and while researchers still do not know why it occurs, they do know how it occurs. A person inherits 23 pairs of chromosomes from each parent. These chromosomes, located inside the body's cells, contain a person's genetic makeup. Each gene is located in a particular place on a chromosome and each does a specific job in helping the body to develop and function normally. Each gene has two variations, called alleles. One allele is inherited from each parent.
Inheritance: LGS is an autosomal dominant disorder, meaning that only one affected allele, inherited from one parent, is enough to cause the disorder. This defect may be passed down from either the mother or father.
Random occurrence: In some cases, the genetic defect randomly occurs during the development of the embryo. In such cases, there is no family history of the disorder. Because LGS is a rare disorder, it is difficult to spot trends in when and in whom it is most likely to occur. It may run in some families, but it appears to affect males and females equally. It is not thought to affect one ethnic group more than another.

Risk factors

General: In some cases, the genetic defect randomly occurs during the development of the embryo. In such cases, there is no family history of the disorder. Because Langer-Giedion syndrome (LGS) is a rare disorder, it is difficult to spot trends in when and in whom it is most likely to occur. It may run in some families, but it appears to affect males and females equally. It is not thought to affect one ethnic group more than another.
Family history: Because LGS is a genetic disorder, people with family histories have an increased risk of developing the condition. A person with LGS has a 50% chance of passing on the damaged chromosome 8 to his/her children.