Maffucci syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Maffucci syndrome is a disorder that primarily affects the bones and skin.

Maffucci syndrome is characterized by:

The severity of the signs and symptoms seen in people with Maffucci syndrome can vary.

The features of Maffucci syndrome usually become apparent in early childhood. Enchondromas develop near the ends of bones, where normal growth occurs. Enchondromas most commonly occur in the bones of the hands and feet. They may also occur in:

Enchondromas may cause bones to become weak and prone to fracture. They may also cause severe bone deformities, which can limit mobility. Enchondromas frequently stop forming in early adulthood.

In people with Maffucci syndrome, vascular lesions typically develop after the enchondromas. They often appear as red or purplish growths on the skin, most commonly on the hands, but they can also affect deep tissues, including organs inside the body. These lesions help distinguish Maffucci syndrome from a similar condition called Ollier disease, which also involves enchondromas. Vascular lesions may worsen over time.

Additional signs and symptoms that may be associated with Maffucci syndrome include:

Although the enchondromas that are associated with Maffucci syndrome start out as benign, they may develop into a type of bone cancer called chondrosarcoma. People with Maffucci syndrome also have an increased risk of other cancers, including cancer of the ovaries, pancreas, liver, brain, and spinal cord.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Genetic changes that contribute to disease are called pathogenic variants. Pathogenic variants in the IDH1 or IDH2 gene can cause Maffucci syndrome. These genes provide instructions for making enzymes called isocitrate dehydrogenases, which help convert a compound called isocitrate into another compound called 2-oxoglutarate. This process also produces a molecule called NADPH, which is necessary for many cellular activities.

The variants in the IDH1 or IDH2 gene that are associated with Maffucci syndrome are somatic, which means that they are acquired during a person’s lifetime and are present only in certain cells. These somatic variants generally occur during early embryonic development. In people with Maffucci syndrome, the somatic variants are typically found within the cells that make up the affected tissues, including the enchondromas and vascular lesions. However, the relationship between these variants and the specific features of Maffucci syndrome is not well understood.

Somatic variants in other genes may account for some cases of Maffucci syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Because the variants in the IDH1 and IDH2 genes that are associated with Maffucci syndrome are acquired during early development, they are not inherited. Affected individuals typically have no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Maffucci syndrome is rare. Since it was first described in 1881, fewer than 300 cases have been reported. However, some researchers believe this number may be an underestimate, since some people with Maffucci syndrome likely do not receive a diagnosis and not all cases are reported in the scientific literature.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Osteolysis · Very frequent (99-80%)

Osteolysis refers to the destruction of bone through bone resorption with removal or loss of calcium.

Venous thrombosis · Very frequent (99-80%)

Formation of a blood clot (thrombus) inside a vein, causing the obstruction of blood flow.

Hemangiomatosis · Very frequent (99-80%)

Multiple enchondromatosis · Very frequent (99-80%)

Bone pain · Frequent (79-30%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.

Exostoses · Frequent (79-30%)

An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage, and arises from a bone that develops from cartilage.

Scoliosis · Frequent (79-30%)

The presence of an abnormal lateral curvature of the spine.

Short stature · Frequent (79-30%)

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Other findings in the same source

From: Orphanet

Additional reported features include Subcutaneous nodule (Frequent (79-30%)); Astrocytoma (Occasional (29-5%)); Breast carcinoma (Occasional (29-5%)); Cerebral palsy (Occasional (29-5%)); Chondrosarcoma (Occasional (29-5%)); Dysphagia (Occasional (29-5%)); Goiter (Occasional (29-5%)); Growth delay (Occasional (29-5%)); Neoplasm of the adrenal cortex (Occasional (29-5%)); Neoplasm of the parathyroid gland (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Maffucci syndrome is Orthopaedics, with a orthopaedic specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What explains the change in pain, movement or function?
• Which activities need adjustment while the diagnosis is being clarified?
• What are the roles of rehabilitation, observation and surgery in this situation?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Maffucci syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.