Fibro-adipose vascular anomaly, also known as FAVA, is a type of vascular anomaly that is both rare and painful. FAVA is characterized by tough fibrofatty tissue taking over portions of muscle, most often contained within a single limb. FAVA also causes

venous Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenate ...

and/or

lymph Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues ...

atic abnormalities. Though FAVA has only been recognized as a distinct vascular anomaly, separate from common venous malformations, within the past ten years, FAVA a distinct

congenital disorder A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities c ...

Signs and symptoms

Common symptoms of FAVA include severe pain and difficulty moving the affected limb, mild enlargement of the affected limb with visible veins, and

contracture In pathology, a contracture is a permanent shortening of a muscle or joint. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spasti ...

. In the cohort described by Alomari et al. from the Vascular Anomalies Center at

Boston Children's Hospital Boston Children's Hospital formerly known as Children's Hospital Boston until 2012 is a nationally ranked, freestanding acute care children's hospital located in Boston, Massachusetts, adjacent both to its teaching affiliate, Harvard Medical Scho ...

, FAVA was located, in descending order, in the

calf Calf most often refers to: * Calf (animal), the young of domestic cattle. * Calf (leg), in humans (and other primates), the back portion of the lower leg Calf or calves may also refer to: Biology and animal byproducts *Veal, meat from calves ...

forearm The forearm is the region of the upper limb between the elbow and the wrist. The term forearm is used in anatomy to distinguish it from the arm, a word which is most often used to describe the entire appendage of the upper limb, but which in ...

wrist In human anatomy, the wrist is variously defined as (1) the carpus or carpal bones, the complex of eight bones forming the proximal skeletal segment of the hand; "The wrist contains eight bones, roughly aligned in two rows, known as the carpal ...

and

thigh In human anatomy, the thigh is the area between the hip ( pelvis) and the knee. Anatomically, it is part of the lower limb. The single bone in the thigh is called the femur. This bone is very thick and strong (due to the high proportion of ...

. The most common presentation is severe

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

. Calf lesions, particularly those located in the posterior compartment, are commonly associated with restricted ankle dorsiflexion (equinus contracture).

Genetics

No one knows what causes FAVA, though recent research revealed mutations in a gene called PIK3CA in some—but not all—cases. PIK3CA is a

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

in the receptor tyrosine kinase phosphatidylinositol 3-kinase (PI3)-AKT growth-signaling pathway. The PIK3CA gene is located on the long (q) arm of

chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans almost 200 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA i ...

. There has been no evidence to suggest that FAVA is inherited or passed along in families.

Diagnosis

FAVA is most often diagnosed in older children, teens and young adults, though it has been diagnosed earlier and later in a patient's life. The constellation of clinical, radiologic, and

histopathologic Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. S ...

findings typically allow the diagnosis of FAVA. The most helpful imaging studies are

ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies f ...

(US) and magnetic resonance imaging (MRI). The major imaging features of FAVA include the presence of complex intramuscular solid

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classif ...

replacing normal muscle fibers with fibrofatty overgrowth and phlebectasia. The extrafascial part is composed of fatty overgrowth, phlebectasia, and occasional lymphatic malformation. The histopathologic findings in FAVA include dense

fibrous tissue Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorpora ...

, fat, and lymphoplasmacytic aggregates within

atrophied Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...

skeletal muscle.

Adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

within skeletal muscles are associated with large, irregular, and sometimes excessively muscularized venous channels and smaller, clustered channels. Organizing thrombi, lymphatic foci and enlarged nerves encircled by dense fibrous tissue are also frequently noted in FAVA.

Management

Some FAVA patients develop limb

; in these cases early orthopedic consultation is necessary.

Achilles tendon The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcane ...

lengthening (heel-cord release) and

physical therapy Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patie ...

can be helpful for treating equinus contracture. Unlike classical venous malformations, pain in FAVA is multifactorial and clinical response to

sclerotherapy Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations (vascular malformations) and also malformations of the lymphatic system. A medicine is injected into the vessels, wh ...

of the venous component can be less effective. While intralesional

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

injections and nerve block may offer temporary or partial pain relief, the source of pain is often the solid intramuscular lesion.

Surgical resection Segmental resection (or segmentectomy) is a surgical procedure to remove part of an organ or gland, as a sub-type of a resection, which might involve removing the whole body part. It may also be used to remove a tumor and normal tissue around it ...

and image-guided percutaneous

cryoablation Cryoablation is a process that uses extreme cold to destroy tissue. Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive, fluids are circulated. Cryoprobes are positioned adjacent to the target in ...

may offer an effective control of pain in FAVA lesions.

Sirolimus Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosi ...

has been effective in improving the quality of life in some people with FAVA.

Signs and symptoms

Genetics

Diagnosis

Management

References

Further reading