On this page
Fibroadipose hyperplasia
This condition typically presents as an enlargement of a limb or digit, or a specific body region, due to the overgrowth of fat and connective tissue. It is caused by genetic changes that occur after conception, meaning it is not usually inherited.
Overview
Fibroadipose hyperplasia is a rare condition where there is an excessive and abnormal growth of both fatty (adipose) and fibrous connective tissues in a localised area of the body. This overgrowth can affect various parts, but it is frequently observed in the limbs or digits, leading to their enlargement or distortion [PMID:33671234]. Unlike many genetic conditions, fibroadipose hyperplasia is not typically inherited from parents; instead, it arises from genetic changes that occur in some body cells after an individual's conception.
The condition is part of a broader group of disorders known as PIK3CA-related overgrowth spectrum (PROS), which are all caused by changes in the PIK3CA gene. The clinical presentation can vary significantly between individuals, even those with the same underlying genetic change, depending on which cells are affected and to what extent [PMID:31535497].
Symptoms & clinical features
The primary symptom of fibroadipose hyperplasia is the presence of localised overgrowth. This can manifest as an enlarged limb, digit (finger or toe), or other body part, which may appear disproportionate to the rest of the body. The affected area often feels soft and doughy due to the excess fatty tissue, but can also have areas of firmer, fibrous tissue.
Depending on the location and extent of the overgrowth, individuals may experience a range of additional symptoms. These can include pain, discomfort, reduced mobility or function of the affected limb, and difficulties with clothing or footwear. Skin changes, such as thickening or abnormal texture, may also be present over the affected area. The impact on daily life can vary significantly, from mild cosmetic concerns to significant functional impairments requiring medical intervention.
Video: Genetics 101
Affected organs
Fibroadipose hyperplasia predominantly affects tissues of mesenchymal origin, which include fat (adipose) and fibrous connective tissues. While the overgrowth is typically localised, it can occur in various body parts. The limbs and digits are commonly affected, leading to an increase in their size and volume. However, other areas such as the trunk, head, or neck can also be involved.
Underlying bones and muscles in the affected region may also be indirectly impacted. The excessive tissue growth can sometimes lead to skeletal abnormalities, such as bone lengthening or deformities, particularly if the overgrowth begins during periods of rapid growth. While the condition primarily affects soft tissues, its presence can influence the structure and function of adjacent organs and systems depending on its location and size.
Risks & severity
The severity of fibroadipose hyperplasia can vary greatly among individuals. Some may have only a subtly enlarged digit, while others may experience significant overgrowth of an entire limb, leading to substantial functional impairment. The extent of the overgrowth can progress over time, particularly during growth spurts in childhood and adolescence.
While fibroadipose hyperplasia itself is not typically life-threatening, its complications can impact quality of life. These may include chronic pain, skin breakdown, infections, or issues with mobility and physical function. In some cases, very extensive overgrowth might affect circulation or nerve function in the affected area. The exact prevalence of fibroadipose hyperplasia is not well established due to its rarity and variable presentation.
Genetic causes
Fibroadipose hyperplasia is caused by changes in the PIK3CA gene (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha). This gene provides instructions for making the p110 alpha protein, a crucial component of the PI3K enzyme. The PI3K enzyme plays a vital role in adding phosphate groups to other molecules, initiating complex signalling pathways within cells [PMID:31535497]. These pathways are essential for regulating numerous cellular processes, including cell growth, proliferation (multiplication), differentiation (specialisation), and survival.
In fibroadipose hyperplasia, the genetic changes in PIK3CA are typically 'somatic' or 'mosaic'. This means the alteration occurs after conception, during early development, and is present only in a proportion of the body's cells, specifically those within the affected overgrowth area. These changes lead to an overactive PI3K pathway, causing cells to grow and divide excessively, resulting in the characteristic overgrowth of fatty and fibrous tissues [PMID:33671234].
- PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alphaThe PIK3CA gene provides instructions for a crucial enzyme involved in fundamental cellular processes such as growth, division, and survival.
Inheritance pattern
Fibroadipose hyperplasia is generally considered a somatic or mosaic condition. This means the genetic change in the PIK3CA gene occurs spontaneously in some cells of the body after the embryo has formed, rather than being inherited from a parent. As a result, only certain tissues or parts of the body are affected by the genetic change, leading to the localised nature of the overgrowth.
Because the genetic changes are somatic, the condition is not typically passed down from parents to children. Individuals with fibroadipose hyperplasia have an extremely low risk of passing the condition on to their offspring. Similarly, unaffected siblings of an individual with fibroadipose hyperplasia are generally not at an increased risk of developing the condition or having children with it.
Diagnosis & testing
Diagnosis of fibroadipose hyperplasia is primarily based on clinical examination, observing the characteristic localised overgrowth of fatty and fibrous tissues. Imaging studies, such as MRI (Magnetic Resonance Imaging), are often used to further characterise the extent of the overgrowth, identify which tissues are involved (fat, fibrous tissue, muscle, bone), and rule out other conditions.
Confirmation of the diagnosis involves genetic testing, typically performed on tissue samples from the affected area, such as a biopsy. This targeted testing aims to identify the specific somatic PIK3CA gene variant responsible for the overgrowth. In the UK, individuals with suspected fibroadipose hyperplasia or other PIK3CA-related overgrowth conditions would typically be referred to a clinical genetics service. Genetic testing for these conditions falls under the NHS Genomic Medicine Service (GMS) pathways, often associated with R-codes for overgrowth syndromes, enabling access to specialist diagnostic services.
Management & lifestyle
Management of fibroadipose hyperplasia focuses on addressing symptoms, improving function, and reducing the impact of the overgrowth. Treatment strategies are highly individualised and depend on the location, size, and severity of the affected area, as well as the symptoms experienced.
Conservative management may include physical therapy to maintain mobility and strength, orthotic devices to support limbs, and compression garments to manage swelling. Surgical intervention may be considered to debulk (remove excess tissue) or reshape the affected area, particularly if the overgrowth causes pain, functional impairment, or significant cosmetic concerns. However, recurrence of overgrowth after surgery can occur. Research is also exploring targeted therapies that specifically inhibit the overactive PI3K pathway, which may offer new treatment avenues for individuals with PIK3CA-related overgrowth conditions.
UK care pathway
In the UK, individuals with suspected fibroadipose hyperplasia would typically enter the care pathway through a referral to a clinical genetics service or a specialist paediatric/adult multi-disciplinary team. Clinical geneticists and genetic counsellors provide comprehensive support, including diagnosis, genetic testing coordination, and counselling. Genetic testing for conditions like fibroadipose hyperplasia is facilitated by the NHS Genomic Medicine Service (GMS), often utilising specific R-codes for overgrowth disorders (e.g., R350 for PIK3CA-related overgrowth), allowing for genomic analysis to identify the causative PIK3CA variant. This pathway ensures access to specialist expertise and coordinated care.
Frequently asked questions
Is fibroadipose hyperplasia inherited?
No, fibroadipose hyperplasia is typically not inherited. It is caused by genetic changes in the PIK3CA gene that occur spontaneously in some body cells after conception. This means it is highly unlikely to be passed down from parents to children.
Can fibroadipose hyperplasia get worse over time?
The overgrowth associated with fibroadipose hyperplasia can sometimes progress or increase in size over time, particularly during periods of rapid growth like childhood or adolescence. Regular monitoring by medical professionals is important to assess any changes.
What kind of doctors treat fibroadipose hyperplasia?
Management often involves a team of specialists, which may include clinical geneticists, orthopaedic surgeons, plastic surgeons, physiotherapists, and pain management specialists. The specific team will depend on the location and extent of the overgrowth.
Are there medications to treat fibroadipose hyperplasia?
Currently, treatments primarily focus on managing symptoms and surgically reducing the overgrowth. However, research is ongoing into targeted therapies that specifically block the overactive PI3K pathway, which may become available in the future.
Does fibroadipose hyperplasia affect mental development?
Fibroadipose hyperplasia itself does not typically affect intellectual or mental development. The condition primarily involves physical overgrowth of tissues. However, the psychosocial impact of living with a visible difference or functional limitation can be significant, and support for this is important.
References
- Adam MP, Bick S, Mirzaa GM. PIK3CA-Related Overgrowth Spectrum. 1993. PMID: 23946963
- Keppler-Noreuil KM, Rios JJ, Parker VE. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. American journal of medical genetics. Part A. 2015. PMID: 25557259
- de Kock L, Cuillerier A, Gillespie M. Molecular characterization of 13 patients with PIK3CA-related overgrowth spectrum using a targeted deep sequencing approach. American journal of medical genetics. Part A. 2024. PMID: 37949664
- McCuaig CC. Update on classification and diagnosis of vascular malformations. Current opinion in pediatrics. 2017. PMID: 28654575
- Takenouchi T, Sakamoto Y, Torii C. Mosaic overgrowth with fibroadipose hyperplasia due to AKT1 mutation. American journal of medical genetics. Part A. 2015. PMID: 25737399
- Lindhurst MJ, Parker VE, Payne F. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nature genetics. 2012. PMID: 22729222
- Vahidnezhad H, Youssefian L, Uitto J. Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS). Experimental dermatology. 2016. PMID: 26268729
- Gökpınar İli E, Taşdelen E, Durmaz CD. Phenotypic and molecular characterization of five patients with PIK3CA-related overgrowth spectrum (PROS). American journal of medical genetics. Part A. 2022. PMID: 35238469