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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Orthopedics · Familial Avascular Necrosis of the Femoral Head

Symptoms, Biology, and Genetics of FANFH

At a Glance

Familial Avascular Necrosis of the Femoral Head (FANFH) is caused by a mutation in the COL2A1 gene that weakens type II collagen, leading to bone death in the hips. Because this collagen is found throughout the body, patients should get immediate baseline eye and hearing exams to check for related conditions.

While Familial Avascular Necrosis of the Femoral Head (FANFH) is centered in the hip, the condition is rooted in a fundamental building block of the human body: type II collagen. Understanding how a single genetic change affects this protein helps explain why the hip joint fails and why other parts of the body might also be affected.

The Role of the COL2A1 Gene

The primary driver of FANFH is a mutation in the COL2A1 gene [1]. This gene is the instruction manual for making type II collagen, a sturdy, rope-like protein that acts as the primary “scaffolding” for cartilage and bone [2][3].

In a healthy hip, this collagen scaffolding is strong enough to withstand the immense pressure of walking and jumping. In FANFH, the mutation often causes a glycine substitution—where a crucial amino acid is replaced by a different one [4][5]. This “typo” in the genetic code makes the collagen strands unstable and prone to structural failure [6][7]. Over time, this weakness compromises the blood vessels inside the bone, leading to the bone death known as osteonecrosis [1][8].

How FANFH is Inherited

FANFH follows an autosomal dominant inheritance pattern [1][9].

  • Autosomal: The gene is located on a non-sex chromosome, meaning it affects males and females equally.
  • Dominant: You only need to inherit one copy of the mutated gene from one parent to develop the condition.

If a parent carries this mutation, there is a 50% chance with each pregnancy that the child will inherit the gene [1]. It is important to note that even family members with the exact same mutation may experience different levels of severity; some may have severe hip pain as teenagers, while others may only develop mild stiffness later in life [10][11].

Beyond the Hip: Type II Collagenopathies

Because type II collagen is used in several parts of the body, FANFH is sometimes considered part of a broader group of disorders called type II collagenopathies [12]. This means that a mutation in the COL2A1 gene can sometimes cause symptoms beyond the hip joint.

Because some of these conditions require urgent medical attention, doctors highly recommend getting baseline eye and hearing exams as soon as you are diagnosed [13]. Conditions associated with this mutation include:

  • Stickler Syndrome: Characterized by eye problems (including a high risk of retinal detachment, which is a medical emergency), hearing loss, and sometimes a cleft palate [14][15].
  • Spondyloepiphyseal Dysplasia Congenita (SEDC): A condition that can cause a shorter-than-average trunk or stature and flattened vertebrae in the spine [9][16].

While some patients only experience hip necrosis, others may find that their “hip problem” is actually linked to these broader systemic conditions [1][17].

Recognizing the Symptoms

The most common symptoms of FANFH are related to the physical breakdown of the femoral head. Because of the genetic nature of the condition, it often affects both hips (bilateral presentation) [18].

  • Deep Hip Pain: Often felt in the groin or buttock, which may start as a dull ache and become sharp when walking [19].
  • Abnormal Gait: Patients may develop a “waddling” gait or a noticeable limp as the hip joint loses its smooth, round shape [10][20].
  • Other Genetic Factors: While COL2A1 is the main culprit, researchers are also looking at other genes like IGF-1 (which affects bone growth) and SOX9 (which helps regulate collagen) to understand why some people are more susceptible to bone death than others [18][21][22].

Common questions in this guide

How is Familial Avascular Necrosis of the Femoral Head inherited?
FANFH is passed down in an autosomal dominant pattern. This means you only need to inherit the mutated COL2A1 gene from one parent to develop the condition, giving each child a 50% chance of inheriting the gene if a parent carries it.
What does the COL2A1 gene have to do with my hip pain?
The COL2A1 gene provides instructions for making type II collagen, which acts as the structural scaffolding for your bones and cartilage. A mutation makes this scaffolding unstable, eventually compromising blood flow and causing bone death in the hip.
Can FANFH affect other parts of my body besides my hips?
Yes, because type II collagen is used in various parts of the body, a mutation can cause systemic issues. Patients with FANFH should get baseline eye and hearing exams, as the mutation is linked to conditions like Stickler Syndrome, which carries a high risk of severe eye emergencies.
What are the earliest symptoms of FANFH?
The earliest symptoms typically include deep pain felt in the groin or buttock that may start as a dull ache and become sharp when walking. Many patients also develop a noticeable limp or a 'waddling' walk as the hip joint shape breaks down.
Will my FANFH symptoms be exactly the same as my parent's?
While family members may carry the exact same COL2A1 mutation, the disease can present very differently. One person might experience severe hip pain as a teenager, while another may only develop mild joint stiffness much later in life.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does the specific COL2A1 mutation found in our family typically lead only to hip issues, or should we be looking for other 'syndromic' signs?
  2. 2.Given the genetic nature of my condition, are there specific activities I should avoid to protect my collagen-weakened joints?
  3. 3.Should my children or siblings have baseline eye exams and hearing tests, even if their hips don't hurt yet?
  4. 4.Can you explain if my mutation is a 'glycine substitution' and what that means for the severity of my disease?
  5. 5.Are there any clinical trials or emerging therapies that specifically target the collagen defect rather than just treating the symptoms?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (22)
  1. 1

    COL2A1 mutation (c.3508G>A) leads to avascular necrosis of the femoral head in a Chinese family: A case report.

    Liu F, Xiong Z, Liu Q, et al.

    Molecular medicine reports 2018; (18(1)):254-260 doi:10.3892/mmr.2018.8984.

    PMID: 29750297
  2. 2

    COL2A1 Gene Mutations: Mechanisms of Spondyloepiphyseal Dysplasia Congenita.

    Nenna R, Turchetti A, Mastrogiorgio G, Midulla F

    The application of clinical genetics 2019; (12()):235-238 doi:10.2147/TACG.S197205.

    PMID: 31824186
  3. 3

    Pathogenicity effects of a COL2A1 missense mutation (c.1594G>C) in cartilage development.

    Zhou J, Yuan T

    Translational pediatrics 2025; (14(7)):1511-1519 doi:10.21037/tp-2025-79.

    PMID: 40800180
  4. 4

    COL2A1 Mutation (c.611G>C) Leads to Early-Onset Osteoarthritis in a Chinese Family.

    Li P, Wang A, Li J, et al.

    International journal of general medicine 2021; (14()):2569-2574 doi:10.2147/IJGM.S310050.

    PMID: 34168485
  5. 5

    Molecular genetics of the COL2A1-related disorders.

    Deng H, Huang X, Yuan L

    Mutation research. Reviews in mutation research 2016; (768()):1-13.

    PMID: 27234559
  6. 6

    A novel de novo mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a Chinese family.

    Xiong Q, Liu Y, Xue Y, et al.

    Human genome variation 2018; (5()):17059 doi:10.1038/hgv.2017.59.

    PMID: 29354277
  7. 7

    Identification of a Novel Mutation in the COL2A1 Gene in a Chinese Family with Spondyloepiphyseal Dysplasia Congenita.

    Huang X, Deng X, Xu H, et al.

    PloS one 2015; (10(6)):e0127529 doi:10.1371/journal.pone.0127529.

    PMID: 26030151
  8. 8

    Skeletal deterioration in COL2A1-related spondyloepiphyseal dysplasia occurs prior to osteoarthritis.

    Rolvien T, Yorgan TA, Kornak U, et al.

    Osteoarthritis and cartilage 2020; (28(3)):334-343 doi:10.1016/j.joca.2019.12.011.

    PMID: 31958497
  9. 9

    Clinical and Molecular Characterization and Discovery of Novel Genetic Mutations of Chinese Patients with COL2A1-related Dysplasia.

    Xu Y, Li L, Wang C, et al.

    International journal of biological sciences 2020; (16(5)):859-868 doi:10.7150/ijbs.38811.

    PMID: 32071555
  10. 10

    Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum

    Yeter B, Kendir Demirkol Y, Eser M, et al.

    Journal of clinical research in pediatric endocrinology 2025; (17(3)):297-306 doi:10.4274/jcrpe.galenos.2025.2024-9-7.

    PMID: 39849673
  11. 11

    Integrated analysis of COL2A1 variant data and classification of type II collagenopathies.

    Zhang B, Zhang Y, Wu N, et al.

    Clinical genetics 2020; (97(3)):383-395 doi:10.1111/cge.13680.

    PMID: 31758797
  12. 12

    Novel variants in COL2A1 causing rare spondyloepiphyseal dysplasia congenita.

    Zheng WB, Li LJ, Zhao DC, et al.

    Molecular genetics & genomic medicine 2020; (8(3)):e1139 doi:10.1002/mgg3.1139.

    PMID: 31972903
  13. 13

    Diagnosis of Prenatal-Onset Achondrogenesis Type II by a Multidisciplinary Assessment: A Retrospective Study of 2 Cases.

    Wang W, Wu Q, Sun L, et al.

    Case reports in obstetrics and gynecology 2019; (2019()):7981767 doi:10.1155/2019/7981767.

    PMID: 31392067
  14. 14

    Genetic testing results of children suspected to have Stickler syndrome type collagenopathy after ocular examination.

    Khan AO, AlAbdi L, Patel N, et al.

    Molecular genetics & genomic medicine 2021; (9(5)):e1628 doi:10.1002/mgg3.1628.

    PMID: 33951325
  15. 15

    Exome sequencing-aided precise diagnosis of four families with type I Stickler syndrome.

    Tian R, Tong P, He Y, et al.

    Molecular genetics & genomic medicine 2024; (12(1)):e2331 doi:10.1002/mgg3.2331.

    PMID: 38073514
  16. 16

    Novel COL2A1 variants in Japanese patients with spondyloepiphyseal dysplasia congenita.

    Akahira-Azuma M, Enomoto Y, Nakamura N, et al.

    Human genome variation 2022; (9(1)):16 doi:10.1038/s41439-022-00193-x.

    PMID: 35581182
  17. 17

    Legg-Calve-Perthes' disease: an opportunity to prevent blindness?

    Wang A, Nixon T, Martin H, et al.

    Archives of disease in childhood 2023; (108(10)):789-791 doi:10.1136/archdischild-2022-325059.

    PMID: 36882306
  18. 18

    IGF-1 polymorphisms modulate the susceptibility to osteonecrosis of the femoral head among Chinese Han population.

    Wang J, Liu H, Zhang Q

    Medicine 2019; (98(23)):e15921 doi:10.1097/MD.0000000000015921.

    PMID: 31169709
  19. 19

    [Total hip replacement in avascular femoral head necrosis].

    Betsch M, Tingart M, Driessen A, et al.

    Der Orthopade 2018; (47(9)):751-756 doi:10.1007/s00132-018-3617-5.

    PMID: 30094647
  20. 20

    Clinical and functional characterization of COL2A1 p.Gly444Ser variant: From a fetal phenotype to a previously undisclosed postnatal phenotype.

    Marchionni E, D'Apice MR, Lupo V, et al.

    Bone reports 2023; (19()):101728 doi:10.1016/j.bonr.2023.101728.

    PMID: 38076483
  21. 21

    SRY-box transcription factor 9 and insulin-like growth factor 1 as potential regulators in the pathogenesis of unilateral condylar hyperplasia: a pilot study.

    Chaurand J, Mondragón-Terán P, Magaña-Quiñones JJ, Godínez-Victoria M

    International journal of oral and maxillofacial surgery 2026; doi:10.1016/j.ijom.2026.02.003.

    PMID: 41720720
  22. 22

    Significant Associations of SOX9 Gene Polymorphism and Gene Expression with the Risk of Osteonecrosis of the Femoral Head in a Han Population in Northern China.

    Song Y, Du Z, Ren M, et al.

    BioMed research international 2016; (2016()):5695317 doi:10.1155/2016/5695317.

    PMID: 28090537

This page provides educational information about the genetics and symptoms of FANFH. It is not a substitute for professional medical advice, genetic counseling, or clinical diagnosis. Always consult your doctor or geneticist about your specific situation.

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