Overview

Do you notice that your child’s head seems larger than expected? You also realise that there is a pink patch that spreads across their skin, and their overall development feels delayed. The condition is called Macrocephaly–Capillary Malformation syndrome (MCAP). 

MCAP is a rare complex condition that affects how your brain, skin and body grow. While the name might sound intimidating, this article will break it down so that anyone can better understand what life looks like with MCAP.¹

What is Macrocephaly–Capillary Malformation syndrome (MCAP)?

MCAP is a genetic overgrowth syndrome. This means that certain parts of the body will either grow too much or develop differently than usual. This happens because of a change or mutation in the PIK3CA gene, which is responsible for how cells grow and divide. 

MCAP is unique as it does not affect every cell in the body. Instead, it is a mosaic condition, which means that only certain cells will be affected. This is why the symptoms can vary so much from person to person, even if they share the same diagnosis.²

Symptoms of MCAP

MCAP can show up in many ways, and not everyone will experience the same set of symptoms. Some of the common symptoms include:

A larger head size (macrocephaly)

Children with MCAP often have a noticeably larger head than their peers. This is often the first thing doctors notice during an examination. The increase in head size can be due to several factors, including: 

• Extra brain tissue (megalencephaly) 
• Extra fluid in the brain (hydrocephalus) 
• Structural brain changes, such as polymicrogyria (too many small folds in the brain) or Chiari malformation (where part of the brain pushes into the spine)

These brain changes may lead to: 

• Delays in sitting, walking, or talking
• Balance or coordination problems 
• Seizures in some children³

Red or pink skin marks 

Most children with MCAP are usually born with flat, red or pink patches on their skin, which are often seen on either the face or limbs. These are known as capillary malformations (CM), widened blood vessels near the skin surface. You might also hear them be called “port-wine stains” or “nevus flammeus.”^2,4

Uneven body growth (asymmetry)

Sometimes, children with MCAP experience uneven growth in their arms and legs, so one side of the body may look larger or longer than the other. This is known as hemihyperplasia. Even though seeing asymmetry might be worrying, it does not always require treatment. However, the difference in size may affect the child’s posture or make daily tasks more challenging.⁵

Delays in development

In MCAP, the brain does not grow or develop in the typical way, which can slow down how children reach their important milestones. Some kids may take longer to sit, walk, or speak. Many also have low muscle tone, which can make them feel floppy as babies. Others may struggle with speech or learning later on. Seizures are also fairly common, mainly when there are brain changes like polymicrogyria.⁶

Facial features and spine concerns

Some children with MCAP may have facial characteristics such as:

• A broad forehead
• Full cheeks
• A smooth area on top of the upper lip (flat philtrum)⁷

Others may have spinal issues, including:

• Scoliosis
• Tethered spinal cord or cysts
• Chiari malformation, which can lead to headaches or dizziness⁵

Diagnosis of MCAP 

As MCAP can show up in so many different ways, diagnosis can be difficult. Doctors usually consider a combination of the child's appearance, development and imaging results to help with diagnosis. Here is how MCAP is usually diagnosed: 

• MRI or CT scans: these imaging tests are used to look for any structural changes in the brain
• Genetic testing: blood, skin or affected tissue samples are used to look for the PIK3CA gene mutation
• Ultrasound or X-rays: these scans help to identify overgrowth in the bones or organs

Even with today’s advanced tools, it is not always possible to get a definite answer. This is true especially when the mutation may not be present in every cell, like in MCAP. This can make confirming the diagnosis more challenging. However, a thorough evaluation can ensure that each child gets the best care possible^.8

Treatment options

Currently, there is no cure for MCAP. However, there are plenty of ways to improve the quality of life by managing the symptoms. This may include:

• Seizure control with medications⁹
• Surgery to manage hydrocephalus (brain fluid buildup) or spinal issues¹⁰
• Therapies (physical, speech, occupational)¹⁰
• Regular check-ups with neurologists, geneticists, or orthopedists¹⁰
• Laser treatments for visible skin marks (if desired)¹⁰

Living with MCAP: what’s the prognosis?

The outlook for children who are diagnosed with MCAP varies a lot, depending on how much of the body is affected and how severe the symptoms are. Some children might only face mild challenges and can lead fairly independent lives. While others may need ongoing support due to developmental delays, seizures or mobility difficulties. Many families share that early therapies, like physical, occupational, and speech therapy, can make a big difference in building skills and boosting quality of life.⁸

What’s new in research? 

Researchers are studying new treatments. Areas of research that are being looked into:¹¹

• Gene therapies
• Stem cell treatments
• Anti-inflammatory drugs to help protect blood vessels and brain tissue

Support for families

Caring for a child who has MCAP can be very stressful. Parents often juggle multiple appointments, therapy sessions and emotional ups and downs. Financial and social challenges can add to the stress. It is definitely not an easy journey. Here are ways to find support:

• Join a rare disease support group to connect with others facing the same problems
• Speak with a genetic counsellor to get some expert guidance
• Ask about supportive services, such as physical, occupational, and speech therapy
• Reach out and connect with other families living with MCAP 

Summary

Macrocephaly–Capillary Malformation syndrome (MCAP) is a rare genetic condition that affects how a child's brain, skin, and body grow. It is caused by a mutation in the PIK3CA gene and is classified as a mosaic condition, meaning not every cell is affected, leading to a wide range of symptoms. Common symptoms of MCAP include a larger head size (macrocephaly), often the first noticeable sign during examinations. This increase in size can result from various factors like extra brain tissue, fluid, or structural changes, which can impact development, coordination and can lead to seizures. Children may also have red or pink skin patches called capillary malformations, usually seen on the face or limbs. Additionally, uneven growth in arms and legs may occur, affecting posture and daily activities.

Developmental delays are common, as children may take longer to reach milestones such as sitting, walking, or speaking, and can also experience low muscle tone or learning challenges. Some may have distinctive facial features and spinal issues, including scoliosis or Chiari malformation, which can cause headaches. Diagnosing MCAP can be complex, relying on a child's physical traits, development, and imaging results like MRIs or genetic testing. Currently, there is no cure for MCAP, but symptoms can be managed through medications, surgeries, therapies, and regular health check-ups. The prognosis varies; some children may lead independent lives, while others may require ongoing support. Research is ongoing in gene therapies, stem cell treatments, and anti-inflammatory drugs. Parents caring for a child with MCAP face significant challenges and are encouraged to seek support through support groups and genetic counselling.