Phelan-McDermid Syndrome

What is Phelan-McDermid syndrome?

Phelan-McDermid syndrome is a rare genetic disorder that may cause a range of medical, intellectual and behavioral concerns. These concerns may include:

• Feeding difficulties.
• Muscle weakness.
• Speech and developmental delays.
• Autism spectrum disorder.
• Epilepsy.

The disorder is also called 22q13.3 deletion syndrome.

How rare is Phelan-McDermid syndrome?

Phelan-McDermid syndrome is very rare. Scientists estimate it occurs in about 2 to 10 of every 1 million live births. However, the condition can be difficult to detect, so it's underdiagnosed. It’s been diagnosed in only about 2,200 to 2,500 people worldwide.

How are Phelan-McDermid syndrome and autism related?

Many people with Phelan-McDermid syndrome also have autism spectrum disorder. Scientists estimate about 1% of people with autism spectrum disorder may also have Phelan-McDermid syndrome.

What causes Phelan-McDermid syndrome?

Phelan-McDermid syndrome is a chromosomal deletion syndrome. Chromosomes are structures inside cells. They contain DNA, and DNA contains genes. Genes are the instructions that control how your body functions. They also determine your traits (like height, eye color and risks for medical conditions).

In a human being, each cell usually contains 23 pairs of chromosomes, for a total of 46. If your child has Phelan-McDermid syndrome, they were born with a piece of chromosome 22 missing or “deleted.”

Most cases of the disorder aren’t inherited. The chromosomal deletion usually happens randomly (spontaneously) when the egg or sperm are forming or during fetal development. But 22q13.3 deletion syndrome can be inherited. A parent who has the condition has a 50% chance of passing it down to each child. One parent can pass it down even if the other parent doesn’t have the condition.

What are the symptoms of Phelan-McDermid syndrome?

The signs and symptoms of Phelan-McDermid syndrome vary widely. They may be mild, moderate or severe. They may appear at birth, during infancy or in early childhood. And they may be physical, behavioral, intellectual or a combination.

Symptoms your child may have include:

• Developmental delay (not hitting milestones at expected times, such as rolling over, sitting up or walking).
• High pain tolerance.
• Muscle weakness (hypotonia).
• Speech problems (absent or delayed ability to talk).
• Sleep disorders.
• Tendency to sweat less than normal, which can lead to overheating and dehydration.
• Trouble eating or swallowing.
• Gastrointestinal issues like frequent nausea and vomiting or gastroesophageal reflux disease.

Many people with Phelan-McDermid syndrome have autism spectrum disorder, which may cause certain behaviors. Your child may:

• Avoid eye contact.
• Be anxious in social situations.
• Obsessively chew things that aren’t food.
• Be oversensitive to touch.

People with 22q13.3 deletion syndrome often have particular physical features. Your child may have:

• Deep-set eyes.
• Drooping eyelids (ptosis).
• Ears that are large or stick out.
• Fusion of their second and third toes (syndactyly).
• Large, fleshy hands or feet.
• A long, narrow head.
• A pointed chin.
• Small or abnormal toenails.

Sometimes the disorder may involve congenital heart conditions and kidney problems. Rarely, people with Phelan-McDermid syndrome have arachnoid cysts (fluid-filled sacs on their brain). They may cause pressure in your child's head, leading to irritability, crying, headaches and epilepsy (seizures).

How is 22q13.3 deletion syndrome diagnosed?

The signs and symptoms associated with Phelan-McDermid syndrome can be subtle and difficult to detect. Your child may have several tests before an accurate diagnosis can be made. To diagnose the condition, your child's healthcare provider may:

• Perform a physical exam.
• Ask about your child's medical history to discuss signs, symptoms and developmental delays.
• Ask about your child's biological family history to determine whether any relatives have had the disorder.
• Request genetic testing to look for the chromosomal deletion. This usually requires a small sample of blood.

In rare cases, Phelan-McDermid syndrome may not be caused by a chromosomal deletion. Instead, it may be caused by a DNA change in the SHANK3 gene. Your healthcare provider may recommend testing for this gene if a deletion isn't found.

If testing confirms 22q13.3 deletion syndrome, your child's healthcare provider may recommend further tests:

• Genetic testing of both parents to see whether the deletion was inherited or spontaneous.
• MRI or CT scan of your child's brain to look for an arachnoid cyst.
• Renal ultrasound to look for kidney defects.
• Echocardiogram to look for heart abnormalities.
• Hearing evaluation.
• Detailed eye exam.
• Sleep study.

Is there a cure for Phelan-McDermid syndrome?

There’s no cure for Phelan-McDermid syndrome. Treatment aims to address your child’s symptoms, maximize their ability to function well and prevent any complications.

Your child’s care team may involve several specialists:

• Cardiologist (heart).
• Gastroenterologist (digestive system).
• Nephrologist (kidney).
• Neurologist (brain).
• Occupational therapist, who can help improve performance with daily activities like eating and writing.
• Orthopaedist (bones and joints).
• Physical therapist, who can help strengthen affected body parts.
• Speech/language pathologist.
• Endocrinologist (hormones).

How can I prevent 22q13.3 deletion syndrome?

There’s no way to repair the genetic changes that lead to Phelan-McDermid syndrome once someone is diagnosed. In rare cases where a parent is also affected, IVF technology or prenatal testing may be used to prevent the disorder in future children.

If you or someone in your family has the disorder, talk to your healthcare provider or genetic counselor. They can help you understand the chances of passing on the disorder.

What is the outlook for my child if they have Phelan-McDermid syndrome?

Each person may have a different outlook, depending on the types of disabilities present and how severe they are.

The effects of the condition are rarely life-threatening. But many people with the disorder require lifelong medical care and may need ongoing social support.

How do I take care of my child with Phelan-McDermid syndrome?

It’s important to take your child to all appointments with specialists to improve function. Because your child may have a decreased ability to sweat:

• Avoid extreme heat.
• Keep your child hydrated.
• Protect them from direct sunlight.

Many people with Phelan-McDermid syndrome have a high tolerance for pain and trouble communicating. So stay alert for cues that your child may be in pain and call their healthcare provider. They can help determine if your child has a stomachache or other issue causing pain. Signs of pain may include:

• Becoming withdrawn or less social.
• Breathing faster than normal.
• Crying or being more irritable than usual.
• Grasping or clutching blankets or other nearby items.
• Keeping their body, arms or legs rigid.
• Making facial expressions like grimacing, holding their eyes tightly shut or pursing their lips.
• Moaning or yelling.

What else can I ask my child's healthcare provider about Phelan-McDermid syndrome?

If your child has Phelan-McDermid syndrome, consider asking their healthcare provider the following questions:

• Was the chromosomal deletion inherited or spontaneous?
• Does my child have any problems with their heart, kidneys or cysts on their brain?
• How extensive will my child's intellectual disability be?
• What specialists should my child see and how often?
• Are there any support groups that can help us cope with this condition?
• Do you recommend genetic counseling?
• Should other people in our family get genetic testing?

A note from Cleveland Clinic

Phelan-McDermid syndrome is a rare genetic disorder. It’s often associated with speech and developmental delays, as well as autism spectrum disorder. If someone in your family has been diagnosed with this chromosomal deletion syndrome, a team of specialists can help. The goals are to improve function, prevent complications and provide genetic counseling.