Maffucci syndrome

Overview

Maffucci syndrome is a rare, non-hereditary congenital disorder characterized by the presence of multiple enchondromas (benign cartilage tumors within bones) and soft tissue hemangiomas (abnormal collections of blood vessels). The condition typically presents during early childhood and progresses throughout life. Maffucci syndrome is often unilateral or asymmetrical, affecting one side of the body more than the other, and leads to skeletal deformities, limb length discrepancies, and an increased risk of malignant transformation, especially into chondrosarcoma.

It is important to distinguish Maffucci syndrome from a similar condition known as Ollier disease, which also involves multiple enchondromas but lacks the vascular anomalies characteristic of Maffucci syndrome. Due to its potential for complications and malignancy, individuals with Maffucci syndrome require lifelong medical surveillance and multidisciplinary care.

Causes

Maffucci syndrome is caused by somatic mutations, meaning the genetic alteration occurs after fertilization and is not inherited from a parent. The most commonly implicated genes are:

• IDH1 (isocitrate dehydrogenase 1)

• IDH2 (isocitrate dehydrogenase 2)

These mutations are believed to disrupt normal cartilage development and vascular formation, resulting in the formation of enchondromas and hemangiomas. Since the mutation is somatic and mosaic in nature, only certain cells and tissues in the body carry the mutation, leading to the asymmetric and patchy distribution of symptoms.

Symptoms

Symptoms of Maffucci syndrome typically appear in early childhood, usually before the age of 10. The most common signs and manifestations include:

• Enchondromas: These are cartilage tumors that most commonly occur in the bones of the hands, feet, arms, and legs. They can cause:

  • Bone deformities

  • Pathological fractures

  • Shortened or unequal limb lengths

• Hemangiomas: Soft tissue vascular tumors that may be visible on the skin or deeper in muscle and connective tissues. They can:

  • Appear as bluish nodules under the skin

  • Cause swelling or discomfort

  • Rarely bleed or become painful

• Skeletal abnormalities: Bowing of long bones, scoliosis, and other bone malformations.

• Functional impairments: Difficulty with mobility or fine motor tasks due to bone and joint involvement.

While the condition is benign, there is a significant risk of transformation of enchondromas into chondrosarcomas and, less commonly, hemangiomas into angiosarcomas or other vascular malignancies.

Diagnosis

The diagnosis of Maffucci syndrome is clinical, supported by imaging and histological studies. Diagnostic methods include:

• Physical examination: Observation of multiple enchondromas and soft tissue hemangiomas, often asymmetrically distributed.

• X-rays: Reveal radiolucent lesions within bones consistent with enchondromas, often causing expansion and deformity.

• MRI and CT scans: Provide detailed views of both bony and soft tissue involvement, useful for surgical planning and identifying any malignant changes.

• Biopsy: May be needed to differentiate benign lesions from malignant transformation, especially in enlarging or painful masses.

• Genetic testing: Detection of IDH1 or IDH2 mutations in affected tissues can support the diagnosis, although it is not always necessary.

Differentiation from other conditions, especially Ollier disease, is essential, primarily based on the presence of hemangiomas in Maffucci syndrome.

Treatment

There is no cure for Maffucci syndrome, and treatment is focused on managing symptoms, preventing complications, and monitoring for malignancy. A multidisciplinary approach involving orthopedists, dermatologists, oncologists, and geneticists is often required. Treatment options include:

• Orthopedic surgery: To correct deformities, stabilize bones, or address fractures.

• Excision of hemangiomas: Performed for cosmetic reasons, discomfort, or if malignancy is suspected.

• Surveillance imaging: Routine X-rays and MRIs to monitor for changes suggestive of malignant transformation.

• Pain management: For chronic discomfort related to bone abnormalities or soft tissue lesions.

• Physical therapy: To improve function and mobility, especially in children with limb asymmetries.

In cases where a lesion is suspected of becoming malignant, prompt surgical intervention and oncological evaluation are essential.

Prognosis

The overall prognosis for individuals with Maffucci syndrome varies depending on the extent of skeletal involvement and the risk of malignant transformation. While many individuals lead functional lives with appropriate management, the risk of cancer significantly influences long-term outlook. Studies estimate that up to 30–40% of patients may develop chondrosarcoma or other malignancies during their lifetime.

With ongoing medical surveillance and timely intervention, many of the complications of Maffucci syndrome can be managed effectively. Early detection of malignancy remains the cornerstone of improving survival and quality of life.

Due to the rarity of the syndrome, affected individuals may benefit from specialized care in centers with experience in skeletal dysplasias and vascular anomalies, as well as access to genetic counseling and psychosocial support.