Mafucci Syndrome

Overview

Mafucci syndrome is a rare congenital disorder of the skin and bones characterized by noncancerous growth of cartilages known as enchondromas, bone deformities, and reddish purple growths within the skin due to abnormal blood vessels. These abnormal blood vessels are called venous hemangiomas as they are present in veins. Enchondromas can sometimes become cancerous (malignant) and convert into Chondrosarcoma, an aggressive cancer of the cartilages.

Cause

In recent years, it was found that a mutation in a gene called IDH1 causes this condition. This mutation takes place during embryonic development so it cannot be considered as a hereditary condition as it is not passed along in the next generations.

Signs and Symptoms

Mafucci syndrome is usually not diagnosed at birth as signs and symptoms appear later between age one to five years.

  • Skeletal Abnormalities: Bony overgrowth is found in long bones called enchondromas. This overgrowth causes distortion and weakness in the bones. Hence fractures of long bones are common. Bulging, bowing of arms and legs, atypical growth and shape is observed over the next few months and years. Adult patients of Mafucci syndrome have a short height due to retarded growth of bones. Enchondromas can turn cancerous, most frequently producing a tumor of the cartilages called chondrosarcoma.
  • Vascular Overgrowth (Hemengiomas): These lesions first appear as soft, compressible and round bluish purple spots at the age of 1-5 years. Over time they become progressive in nature and become hard and may contain calcium deposits. Hands are the most common sites where these occur. Other parts affected include the coverings of the brain and spinal cord called meninges, the oral cavity and tongue. Abnormal veins are the original location of hemengiomas.

Complications

Enchondromas can turn cancerous and convert into chondrosarcomas, which is an aggressive tumor of the cartilages. Patients of Mafucci syndrome are also at an increased risk of developing ovarian and liver cancer.

Diagnosis

Diagnosis is mostly based on signs and symptoms, physical examination and radiological investigation usually employing X-ray only. Examination of the specimen can reveal benign, non-aggressive nature of the cells under microscope indicating enchondromas.

Three conditions having a similar pattern of manifestations must be considered during diagnosis in order to rule them out:

  1. Ollier Disease: Similar bony deformities are found but no venous hemengiomas occur in Ollier disease.
  2. Proteus Syndrome: It is a condition having similar venous lesions as seen in Mafucci syndrome. However, cause is different as mutation occurs in the gene AKT1 during embryonic development.
  3. Blue Rubber Bleb Nevus Syndrome: No abnormal bony changes are found like in Mafucci syndrome but the venous lesions have a very similar presentation.
    Mafucci Syndrome

    X-Ray of hands revealing bony overgrowth at multiple points (Source: radiographics.rsna.org)

Treatment

Treatment of Mafucci syndrome is based on managing signs and symptoms. Several factors are considered before treating the venous hemengiomas such as their location, frequency, progression and number. Anticoagulant therapy, compression dressing, laser treatment and sclerotherapy are often used when managing the hemengiomas. Another therapy with varied degree of success is now considered in which a drug called rapamycin is injected into the sites of lesions. Surgical excision can also be performed to completely remove the lesions.

As for treating the bone deformities, several procedures are present. A surgery can be performed during childhood to lengthen the long bones of the limbs. Abnormal curving of the spine called scoliosis can also be corrected during early childhood when Mafucci syndrome is detected.

Sources

https://rarediseases.org/rare-diseases/maffucci-syndrome/

https://ghr.nlm.nih.gov/condition/maffucci-syndrome#diagnosis

https://emedicine.medscape.com/article/1111804-overview#a5

https://radiopaedia.org/articles/maffucci-syndrome