Maffucci syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at November 12, 2016
StartDiseasesMaffucci syndrome

Maffucci syndrome was first recognized by Italian pathologist Angelo Maffucci in 1881. This rare genetic disorder gradually worsens over time, but it does not necessarily harm a person's quality of life. With proper treatment, people with Maffucci syndrome can enjoy a normal lifespan.

Contents

Definition & Facts

Maffucci syndrome is a genetic condition that manifests during childhood or early puberty. The primary characteristic of Maffucci syndrome is enchondromas in the arms and legs. These are benign cartilage overgrowths, so these cartilaginous tumors typically are not cancerous.

Patients with Maffucci syndrome also deal with abnormal skeletal growth, skin lesions, and benign vascular tumors. Though all of these abnormal growths are not cancerous, patients with Maffucci syndrome have a higher risk of developing malignant tumors later in life.

Symptoms & Complaints

Normally, the first sign of Maffucci syndrome is lesions that develop between the ages of one to five years. These lesions are round spots that start out compressible but eventually become stiff and may seem like knots. They may appear to be red, purple, or blue. These lesions most commonly occur on the skin, but they are formed from abnormal veins, so they can show up on internal membranes or the tongue.

The lesions may not be noticed if they are internal, so some people do not experience difficulties until they develop enchondromas. These tumorous cysts develop in the cartilage around and within the bones. They cause bones to become distorted and weakened, so patients may have bulging or bent bones that break more easily. The enchondromas often cause one bone to grow more quickly or slowly than its counterpart, so people with Maffucci syndrome often end up with legs and arms that are different lengths.

Patients with Maffucci syndrome are generally short in stature, and their muscles may be underdeveloped in areas. Occasionally, the skin lesions and cartilage tumors are accompanied by lymphangiomas which are malformed cysts made of lymph node cells. Generally, all of the abnormal growths associated with Maffucci syndrome are not severe enough to limit daily activities or hamper intelligence.

Later in life, Maffucci syndrome is accompanied by a higher risk of malignant tumors. These tumors are particularly likely to be bone cancers, but some also develop liver cancer or ovarian cancer.

Causes

Maffucci syndrome is a genetic disorder, but it is not inherited. Instead of inheriting a mutated gene from a parent, patients with Maffucci syndrome suffer from what is called a somatic mutation. This occurs when a single cell mutates spontaneously before birth. As the fetus grows, the single cell divides several times, and all cells that derive from the mutated cell share the mutation.

In 2011, research discovered that the precise cell mutation for Maffucci syndrome arose from the IDH1 or IDH2 gene. These genes are responsible for creating isocitrate dehydrogenase enzymes that normally regulate metabolism. When the enzyme function properly, it turns nutrients into the energy needed to create new cells.

The abnormal version of the enzyme causes certain cells in the body to metabolize energy incorrectly and grow excessively. This abnormal cell overgrowth eventually causes the benign tumors to develop. Though the tumors are not necessarily malignant, having excessive benign tumors will increase a person's risk of a cell becoming cancerous.

Diagnosis & Tests

Maffucci syndrome is typically diagnosed after a parent notices unusual lumps, lesions, or growths occurring on their child. However, it can be difficult to get a prompt diagnosis because the early symptoms of Maffucci syndrome are not extremely recognizable.

The skin lesions that often appear in early childhood may be the first sign of Maffucci syndrome, but when they are still small, they can be misdiagnosed as a simple mole or wart. If the enchondromas are growing inside of bones, they may not create noticeable lumps. Sometimes, the condition is not suspected until a child breaks a bone and an X-ray reveals the enchondroma.

When the tumor is first diagnosed, doctors will need to do a biopsy to confirm that it is a benign enchondroma and not a cancerous tumor. This will require removing a small portion of the tumor and studying it in a lab.

If a physical examination and medical history show that a patient has the classic symptoms of Maffucci syndrome, genetic testing will be done to confirm the diagnosis. A study of genetic material can show whether or not the IDH1 and IDH2 genes show the mutation that causes Maffucci syndrome. 

Treatment & Therapy

Treatment plans for patients with Maffucci syndrome mostly rely on treating the symptoms. If a patient does not have any tumors or lesions, they do not need any treatment. Instead, they will just need regular checkups to look for the conditions associated with Maffucci syndrome. Lesions are not always treated unless they become uncomfortable or bother the patient. They can be shrunk with injections of a sclerosing agent that prevents the lesion from growing.

Surgical removal is also an option for large lesions or enchondromas. Removing cartilage tumors before they grow too big will keep them from deforming the bone. If the condition is not diagnosed promptly, a patient may already be dealing with skeletal abnormalities.

There are many other surgeries that can be used to correct issues like uneven leg length or scoliosis. These surgeries may include grafts to strengthen the bone or removal of uneven bone fragments. If the Maffucci syndrome is affecting the delicate bones of the hand, the patient may require surgery from a specialist.

Prevention & Prophylaxis

Because it is caused by a random genetic mutation, there is no known way of preventing Maffucci syndrome from developing. However, it is possible to prevent the more severe symptoms of the condition from affecting daily life.

Regular checkups can diagnose and treat any enchondromas before they get big enough to cause skeletal deformities. It is also important to get regular checkups so doctors can find any cancerous tumors before it is too late to attempt treatment.