Osteopetrosis

What causes osteopetrosis?

The various types of osteopetrosis are caused by genetic changes (mutations) in one of at least ten genes. There is nothing a parent can do before, during or after a pregnancy to cause osteopetrosis in a child.

The genes associated with osteopetrosis are involved in the development and/or function of osteoclasts, cells that break down bone tissue when old bone is being replaced by new bone (bone remodeling). This process is necessary to keep bones strong and healthy. Mutations in these genes can lead to abnormal osteoclasts, or having too few osteoclasts. If this happens, old bone cannot be broken down as new bone is formed, so bones become too dense and prone to breaking.

  • Mutations in the CLCN7 gene cause most cases of autosomal dominant osteopetrosis, 10-15% of cases of autosomal recessive osteopetrosis (the most severe form), and all known cases of intermediate autosomal osteopetrosis.
  • Mutations in the TCIRG1 gene cause about 50% of cases of autosomal recessive osteopetrosis.
  • Mutations in the IKBKG gene cause X-linked osteopetrosis.
  • Mutations in other genes are less common causes of osteopetrosis.
  • In about 30% percent of affected people, the cause is unknown.

People with questions about the specific cause of osteopetrosis in themselves or a family member are encouraged to speak with a genetics professional.

Last updated on 05-01-20

Is genetic testing available for osteopetrosis?

Yes. Genetic testing for the various subtypes of osteopetrosis is available. Genetic testing can be used to confirm the diagnosis and to differentiate between different subtypes of osteopetrosis. This may provide additional information regarding the long-term outlook (prognosis), likely response to treatment, and recurrence risks.

The Genetic Testing Registry (GTR) is a central online resource for information about genetic tests. The intended audience for the GTR is health care professionals and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. Click on the link above to view the information that the GTR provides about genetic testing for osteopetrosis.

Last updated on 05-01-20

How is osteopetrosis inherited?

Inheritance of the various subtypes of osteopetrosis can be autosomal dominant (most commonly), autosomal recessive, or X-linked recessive. The most severe forms are autosomal recessive.

  • In autosomal dominant inheritance, having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. Most people with autosomal dominant osteopetrosis inherit the condition from an affected parent. Each child of a person with this form has a 1 in 2 (50%) chance of being affected.
  • In autosomal recessive inheritance, in order to be affected a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
    • 25% (1 in 4) chance to be affected
    • 50% (1 in 2) chance to be an unaffected carrier like each parent
    • 25% chance to be unaffected and not be a carrier
  • X-linked recessive conditions usually occur in males, who only have one X chromosome (and one Y chromosome). Females have two X chromosomes, so if they have a gene mutation on one of them, they still have a normal copy on their other X chromosome. For this reason, females are typically unaffected. While females can have an X-linked recessive condition, it is very rare.

If a mother is a carrier of an X-linked recessive condition and the father is not, the risk to children depends on each child's sex.

* Each male child has a 50% chance to be unaffected, and a 50% chance to be affected
* Each daughter has a 50% chance to be unaffected, and a 50% chance to be an unaffected carrier

If a father has the condition and the mother is not a carrier, all sons will be unaffected, and all daughters will be unaffected carriers.

Last updated on 05-01-20

Will osteopetrosis affect my child?

The chance for a person with osteopetrosis to have an affected child depends on the type of osteopetrosis present and how it is inherited. For example, for those with the more common adult form (inherited in an autosomal dominant manner), there is a 50% chance to pass the disease-causing gene to each child.

People with personal questions about the chance to have an affected child are encouraged to speak with a genetic counselor or other genetics professional. A genetics professional can help by:

  • thoroughly evaluating the family history
  • addressing questions and concerns
  • assessing recurrence risks
  • facilitating genetic testing if desired
  • discussing reproductive options

Last updated on 05-01-20

How might future symptoms or complications associated with osteopetrosis be prevented?

Measures that may be taken to prevent signs and symptoms of osteopetrosis depend on the type of osteopetrosis a person has.

For people with autosomal recessive osteopetrosis, the most severe form, allogenic hematopoietic stem cell transplantation (HSCT) can cure the condition. Most signs and symptoms (bone sclerosis, bone marrow failure, and extramedullary hematopoiesis) can be prevented or reversed by HSCT. Secondary neurosensory impairments caused by nerve compression may be prevented by early HSCT, but not reversed when they are already present. The decision of whether a person is a candidate for HSCT is made on a case-by-case basis.

For people with autosomal dominant osteopetrosis, with onset usually in childhood or adulthood, good routine dental care and oral hygiene may help prevent osteomyelitis of the mandible (infection in the jaw bone).

People with personal questions about options for preventing symptoms or complications of osteopetrosis should speak with their health care professional.

Last updated on 05-01-20

Who should I speak with regarding my questions about the management of osteopetrosis?

A number of specialists may be needed to treat people with osteopetrosis. Medical management (aside from transplant) is usually done by an endocrinologist who is comfortable with, and knowledgeable of, metabolic bone disease. People with osteopetrosis who have scoliosis should see a spine specialist who is familiar with the condition. An orthopedic surgeon familiar with osteopetrosis should manage treatment for fractures and other problems with the bones and joints. It is also important to see an ophthalmologist (eye doctor) or neuro-ophthalmologist to follow or treat vision changes or vision loss.

The OsteoPETrosis Society website provides the names of several experts and a physician referral list for people with osteopetrosis looking for doctors with knowledge of the condition.

Last updated on 05-01-20

Are there specific diet recommendations for people with osteopetrosis?

There is little information in the medical literature about nutrition and dietary recommendations for people with osteopetrosis. We are not aware of any specific dietary guidelines that have been proposed.

Generally, nutritional support in childhood is important to improve growth. It also may enhance responsiveness to other treatments. A low-calcium and high-phosphate diet in conjunction with oral prednisone has led to improvement in anemia, thrombocytopenia, and bone density in a few patients. However, some people may need calcium if hypocalcemia or rickets becomes a problem. Vitamin D supplements may help by stimulating dormant osteoclasts, thus stimulating bone resorption.

Last updated on 05-01-20

What is the long-term outlook for people with osteopetrosis?

The long-term-outlook (prognosis) for people with osteopetrosis depends on the subtype and the severity of the condition in each person.

The severe infantile forms of osteopetrosis are associated with shortened life expectancy, with most untreated children not surviving past their first decade. Bone marrow transplantation seems to have cured some infants with early-onset disease. However, the long-term prognosis after transplantation is unknown. For those with onset in childhood or adolescence, the effect of the condition depends on the specific symptoms (including how fragile the bones are and how much pain is present). Life expectancy in the adult-onset forms is normal.

Last updated on 05-01-20

How might osteopetrosis be treated?

Treatment for osteopetrosis depends on the specific symptoms present and the severity in each person. Therefore, treatment options must be evaluated on an individual basis.

Nutritional support is important to improve growth and it also enhances responsiveness to other treatment options. A calcium-deficient diet has been beneficial for some affected people.

Treatment is necessary for the infantile form:

  • Vitamin D (calcitriol) appears to stimulate dormant osteoclasts, which stimulates bone resorption. Large doses of calcitriol with restricted calcium intake sometimes improves osteopetrosis dramatically, but the improvement seen with calcitrol is not sustained when therapy is stopped.
  • Gamma interferon can have long-term benefits. It improves white blood cell function (leading to fewer infections), decreases bone volume, and increases bone marrow volume.
  • Erythropoietin can be used for anemia, and corticosteroids can be used for anemia and to stimulate bone resorption.

Bone marrow transplantation (BMT) markedly improves some cases of severe, infantile osteopetrosis associated with bone marrow failure, and offers the best chance of longer-term survival for individuals with this type.

In pediatric (childhood) osteopetrosis, surgery is sometimes needed because of fractures.

Adult osteopetrosis typically does not require treatment, but complications of the condition may require intervention. Surgery may be needed for aesthetic or functional reasons (such as multiple fractures, deformity, and loss of function), or for severe degenerative joint disease.

Last updated on 05-01-20

Name: Osteopetrosis Support Trust Email: http://www.osteopetrosis-support-trust.org.uk/what-is-osteopetrosis/#contact Url: http://www.osteopetrosis-support-trust.org.uk/
Name: The OsteoPETrosis Society OPETS Phone: 980-292-3921 Email: osteopetrosispatient@gmail.com,janecastello.opets@gmail.com Url: http://www.osteopetrosis.org/ Facebook page: https://www.facebook.com/osteopetrosis

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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