National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Familial avascular necrosis of the femoral head


Other Names:
Familial osteonecrosis of the femoral head; Primary avascular necrosis of the femoral head
Categories:
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. 
Last updated: 2/4/2019
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]
Last updated: 2/4/2019

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.

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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
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Last updated: 7/1/2020
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.   


Last updated: 2/4/2019
Most cases of avascular necrosis of the femoral head (ANFH) are not inherited in families. In a few rare families, ANFH is inherited in an autosomal dominant pattern.[1] All individuals inherit two copies of each gene. In inherited ANFH, an individual has a disease-causing mutation in only one copy of the gene that causes the person to have the disease. The mutation can be inherited from either parent. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this.

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the mutation and the condition. Offspring who inherit the mutation will have the condition, although they could be more or less severely affected than their parent.   

Last updated: 2/4/2019
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.
Last updated: 2/4/2019

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.
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]
Last updated: 2/4/2019
The long-term outlook for avascular necrosis of the femoral head depends on the stage that it is diagnosed. Most people with this condition will end up having arthritis in the joint as well as hip collapse. Children diagnosed with this condition have a better long term outlook than adults. [2] 
Last updated: 2/4/2019

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Familial avascular necrosis of the femoral head. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Le Merrer M. Familial avascular necrosis of femoral head. Orphanet. May 2008; http://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/.