Megalencephaly-capillary malformation syndrome

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What is megalencephaly-capillary malformation syndrome?

Megalencephaly-capillary malformation syndrome (MCAP) is a disorder characterized by overgrowth of several tissues in the body. Its primary features are a large brain (megalencephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).

In individuals with MCAP, megalencephaly leads to an unusually large head size (macrocephaly), which is typically evident at birth. After birth, the brain and head continue to grow at a fast rate for the first few years of life; then, the growth slows to a normal rate, although the head remains larger than average. Additional brain abnormalities are common in people with MCAP; these can include excess fluid within the brain (hydrocephalus) and abnormalities in the brain's structure, such as those known as Chiari malformation and polymicrogyria. Abnormal brain development leads to intellectual disability in most affected individuals and can also cause seizures or weak muscle tone (hypotonia). In particular, polymicrogyria is associated with speech delays and difficulty chewing and swallowing.

The capillary malformations characteristic of MCAP are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations usually look like pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, particularly the nose, the upper lip, and the area between the nose and upper lip (the philtrum). In other people with MCAP, the malformations appear as patches spread over the body or as a reddish net-like pattern on the skin (cutis marmorata).

In some people with MCAP, excessive growth affects not only the brain but other individual parts of the body, which is known as segmental overgrowth. This can lead to one arm or leg that is bigger or longer than the other or a few oversized fingers or toes. Some affected individuals have fusion of the skin between two or more fingers or toes (cutaneous syndactyly).

Additional features of MCAP can include flexible joints and skin that stretches easily. Some affected individuals are said to have doughy skin because the tissue under the skin is unusually thick and soft.

The gene involved in MCAP is also associated with several types of cancer. Although a small number of individuals with MCAP have developed tumors (in particular, a childhood form of kidney cancer known as Wilms tumor and noncancerous tumors in the nervous system known as meningiomas), people with MCAP do not appear to have a greater risk of developing cancer than the general population.

How common is megalencephaly-capillary malformation syndrome?

The prevalence of MCAP is unknown. At least 150 affected individuals have been reported in the medical literature. Because the condition is often thought to be misdiagnosed or underdiagnosed, it may be more common than reported.

What genes are related to megalencephaly-capillary malformation syndrome?

MCAP is caused by mutations in the PIK3CA gene, which provides instructions for making the p110 alpha (p110α) protein. This protein is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K), which plays a role in chemical signaling within cells. PI3K signaling is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, and cell survival. These functions make PI3K important for the development of tissues throughout the body, including the brain and blood vessels.

PIK3CA gene mutations involved in MCAP alter the p110α protein. The altered subunit makes PI3K abnormally active, which allows cells to grow and divide continuously. Increased cell proliferation leads to the overgrowth of the brain, blood vessels, and other organs and tissues characteristic of MCAP.

How do people inherit megalencephaly-capillary malformation syndrome?

MCAP is not inherited from a parent and does not run in families. In people with MCAP, a PIK3CA gene mutation arises randomly in one cell during the early stages of development before birth. As cells continue to divide, some cells will have the mutation and other cells will not. This mixture of cells with and without a genetic mutation is known as mosaicism.

Where can I find information about diagnosis or management of megalencephaly-capillary malformation syndrome?

These resources address the diagnosis or management of megalencephaly-capillary malformation syndrome and may include treatment providers.

You might also find information on the diagnosis or management of megalencephaly-capillary malformation syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about megalencephaly-capillary malformation syndrome?

You may find the following resources about megalencephaly-capillary malformation syndrome helpful. These materials are written for the general public.

MedlinePlus - Health information (2 links)
Additional NIH Resources - National Institutes of Health
National Institute of Neurological Disorders and Stroke: Megalencephaly
Educational resources - Information pages (4 links)
Patient support - For patients and families (3 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary
Genetic Testing Registry - Repository of genetic test information (1 link)
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for megalencephaly-capillary malformation syndrome?

macrocephaly-capillary malformation syndrome
macrocephaly cutis marmorata telangiectatica congenita
MCAP
M-CM
MCMTC
megalencephaly-capillary malformation-polymicrogyria syndrome
megalencephaly cutis marmorata telangiectatica congenita

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about megalencephaly-capillary malformation syndrome?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding megalencephaly-capillary malformation syndrome?

cancer ; capillaries ; cell ; cell proliferation ; cM ; cutaneous ; enzyme ; gene ; hydrocephalus ; hypotonia ;kidney ; kinase ; macrocephaly ; malformation ; megalencephaly ; mosaicism ; muscle tone ; mutation ;nervous system ; philtrum ; population ; prevalence ; proliferation ; protein ; subunit ; syndactyly ;syndrome ; tissue ; tumor ; Wilms tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (4 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.