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Disease Profile

Familial avascular necrosis of the femoral head

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adult

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ICD-10

M87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Familial osteonecrosis of the femoral head; Primary avascular necrosis of the femoral head

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

Avascular necrosis of the femoral head (ANFH) is a degenerative condition which causes the upper ends of the thigh bones (femurs) to break down due to a disrupted blood supply and poor bone repair.[1] It can lead to pain and limping, hip collapse, and cause the legs to be of unequal length.[2] The development of ANFH is associated with steroid use, alcohol use, smoking, auto-immune disorders, and other medical conditions such as sickle cell anemia. Less commonly, ANFH can occur as the result of trauma to the hip, such as a hip fracture or hip surgery. Around 20,000-30,000 cases are reported each year in the United States. This condition mainly affects young, active adults, but can occur in children as well. In children, ANFH is known as Legg-Calves-Perthes disease. Most people with ANFH do not have a family history of this condition, but there are some very rare inherited forms of ANFH.[2][3]

ANFH is usually diagnosed by X-rays or an MRI. Treatment depends on how much damage is present in the bone, and may involve surgery.[4] Total hip replacement is an option for those with advanced ANFH. Early diagnosis is associated with a better outcome, but is difficult because ANFH doesn’t cause any symptoms in its earliest stages. 

Symptoms

In the early stages, avascular necrosis of the femoral head does not cause any symptoms. As the bone damage increases, people may have leg and hip pain, a limited ability to move the leg, and a limp. Some people may develop a difference in the length of their legs. Eventually, the hip joint breaks down and surgery may be required.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Groin pain
0031520
30%-79% of people have these symptoms
Flattened femoral head
Flat head of thigh bone
0008812
Hip osteoarthritis
0008843
Hip pain
0030838
Impairment of activities of daily living
0031058
Limited hip movement
0008800
Lower limb asymmetry
Left and right leg differ in length or width
0100559
Short stepped shuffling gait
Short stepped shuffling walk
0007311
5%-29% of people have these symptoms
Generalized osteoporosis
0040160
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Avascular necrosis of the capital femoral epiphysis
0005743

Cause

Although rare, there are some families that have an inherited form of ANFH.[1] Genetic changes in the type II collagen gene (COL2A1) cause ANFH in a few families.[5] This gene is responsible for making a protein that helps build cartilage. One other family was found to have a genetic change in the transient receptor potential vanilloid 4 gene (TRPV4).[6][7] This gene makes a protein that helps regulate blood flow.

In the non-inherited types of avascular necrosis of the femoral head, the cause is not clear. These are some of the factors have been associated with an increased chance to get ANFH:[2][6][1]

Steroid use
Alcohol use
Chemotherapy
Auto-immune disease
Medications that suppress the immune system
Sickle cell anemia and other disorders of the blood
Disorders that affect how the blood clots 
Too much fat in the bloodstream (hyperlipidemia

ANFH can also develop in a person who has had a hip injury (like a fracture or dislocation) or hip surgery.

Diagnosis

Avascular necrosis of the femoral head is diagnosed based the symptoms, and by using imaging, such as X-rays or MRI. A physical examination can be helpful as well.[3] People with the familial (inherited) form of ANFH may have other family members with the same condition.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment

Treatment for avascular necrosis of the femoral head may depend on how early it is diagnosed and the presence of an underlying condition. It is not clear if medications are helpful.[8] Surgery may help in some cases.[2][4] In the more advanced stages, total hip replacement is an option.[4]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Familial avascular necrosis of the femoral head. This website is maintained by the National Library of Medicine.

    In-Depth Information

    • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
    • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
    • PubMed is a searchable database of medical literature and lists journal articles that discuss Familial avascular necrosis of the femoral head. Click on the link to view a sample search on this topic.

      References

      1. Le Merrer M. Familial avascular necrosis of femoral head. Orphanet. May 2008; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86820.
      2. Wang T, Azeddine B, Mah W, Harvey EJ, Rosenblatt D, Seguin C.. Osteonecrosis of the femoral head: genetic basis.. Int’l Orthoped. Oct 17, 2018; 1-12. https://www.ncbi.nlm.nih.gov/pubmed/30328481.
      3. Choi HR, Steinberg ME, Y Cheng E. Osteonecrosis of the femoral head: diagnosis and classification systems. Curr Rev Musculoskelet Med. 2015; 8(3):210-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596207/.
      4. Chughtai M, Piuzzi NS, Khlopas A, Jones LC, Goodman SB, Mont MA. An evidence-based guide to the treatment of osteonecrosis of the femoral head. Bone Joint J. Oct 2017; 99-B(10):1267-1279. https://www.ncbi.nlm.nih.gov/pubmed/28963146.
      5. Avascular necrosis of the femoral head, primary 1; ANFH1. Online Mendelian Inheritance in Man (OMIM). Updated Mar 2, 2017; https://www.omim.org/entry/608805.
      6. Mah W, Sonkusare SK, Wang T, Azeddine B, Pupavac M, Carrot-Zhang J et al. Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head. J Med Genet. 2016; 53:705-709. https://www.ncbi.nlm.nih.gov/pubmed/27330106.
      7. Avascular necrosis of the femoral head, primary 2; ANFH2. Online Mendelian Inheritance in Man (OMIM). Mar 2, 2017; https://www.omim.org/entry/617383.
      8. Lee YJ, Cui Q, Koo KH. Is There a Role of Pharmacological Treatments in the Prevention or Treatment of Osteonecrosis of the Femoral Head?: A Systematic Review. J Bone Metab. Feb 2019; 26(1):13-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416144/.

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