An Overview of Phelan-McDermid Syndrome

Phelan-McDermid Syndrome (PMS) is a rare genetic condition also referred to as 22q13 deletion syndrome. At the present time, it’s unclear how many people have the disorder. As of 2017, more than 1,500 individuals had registered with the Phelan-McDermid Syndrome Foundation (PMSF) in Venice, Florida, however, this does not account for the worldwide incidences of PMS, as not all families enter the registry. PMS is likely to affect both males and females equally.

The syndrome was first described in 1985 in the medical literature. In 1988, a group of doctors highlighted a case they had seen where a patient was missing a part of the long arm of chromosome 22 at the Society of Human Genetics meeting. In 2002, a group of parents suggested that the official name of the syndrome should be called Phelan-McDermid Syndrome, after Dr. Katy Phelan and researcher Heather McDermid from the University of Alberta. In 2003, 22q13 deletion syndrome officially became known as Phelan-McDermid Syndrome.

Symptoms

Most children with PMS grow normally in utero and directly following the birth. Children with PMS are most likely to demonstrate signs and symptoms within the first six months of life.

Parents may notice their child has difficulty with skills like rolling over, sitting up, or walking. These observable symptoms often prompt parents to seek the advice of their doctor as to why the child isn’t able to achieve these developmental milestones.  

The symptoms and their severity differ from person to person, but there are some common characteristics associated with PMS:

• Low muscle tone in newborns, also known as neonatal hypotonia
• Poor head control
• A weak cry
• Speech is delayed or absent
• Developmental delays across several areas referred to as global developmental delays (GDD)
• Abnormalities in facial structures, such as a longer head shape than expected, deep-set eyes, large ears, and more.
• Large, fleshy hands
• Toenail deformities
• Reduced ability to perspire
• Less commonly, defects of the heart or kidneys

As the child grows older, other symptoms can follow, such as:

• Moderate to severe developmental and intellectual impairments
• A diagnosis of an autism spectrum disorder
• Behavioral challenges
• Sleep disturbances
• Difficulty with toilet training
• Eating and swallowing problems
• Seizures
• Diminished ability to perceive pain
• Symptoms of DiGeorge syndrome.

Causes

PMS is a genetic condition caused by the deletion of the long portion of chromosome 22 in the area of 22q13 or a mutation in the gene known as SHANK3. Although the SHANK3 gene is a significant contributing factor in PMS, the aspects that control the severity of the condition are poorly understood.

To further explain, most cases of PMS happen because a portion of an individual’s chromosome is absent, a process known as a deletion. Oftentimes, the deletion occurs as a new event (de novo) in the person’s body, as opposed to being passed down from a parent.

In approximately 20 percent of cases of PMS, the deletion occurs due to a process known as chromosomal translocation, in which one or more arms from chromosomes detach and change places.

Another way PMS may develop is through a mutation in the SHANK3 gene. Like the deletion, mutations are generally new events as well, and not an inherited variant from a parent.

Diagnosis

A physician may suspect a diagnosis of PMS based on symptoms like low muscle tone in newborns, delays in speech, and intellectual disabilities. However, an individual may undergo several tests before a definitive diagnosis is given.

Initially, the healthcare professional will take a detailed history, perform a physical exam, and may order tests like magnetic resonance imaging (MRI).

Genetic testing will also be an integral part of the diagnostic process. The most common genetic test is a blood draw called a chromosomal microarray. This type of testing helps to discover whether or not a segment of chromosome 22 has been deleted. Additionally, another genetic test can be used to assess variations in the SHANK3 gene.

Treatment

Currently, treatment for PMS is aimed at managing the array of symptoms a person may be experiencing—there is no specific treatment for the condition.

To address the wide range of needs a person with PMS might have, patients and their families may need to assemble a medical team of professionals, like a pediatrician, neurologist, genetic counselor, and physical, occupational, and speech therapists, to establish a plan of care for multiple areas of concern.

Additionally, researchers are developing clinical trials for PMS to identify new treatment options.

Coping

If your child is diagnosed with PMS, that condition will play a role in most decisions you make for the well-being of your family. You may be required to make decisions about your child’s medical care, your living situation, financial concerns, and more. Furthermore, those decisions may differ depending on the severity of the symptoms your child experiences.

You may need to reach out to your child’s doctors, therapists, schools, and local, state, and federal agencies. Know that it’s perfectly reasonable to need some guidance and support from time to time as you advocate for your child’s care.

A Word From Verywell

A diagnosis of PMS can be overwhelming for families, and the terminology associated with a genetic condition may feel confusing at times. When creating your medical team, make sure you have healthcare providers with whom you feel you can effectively communicate your questions and concerns. Although there is still a lot to learn about PMS, additional funds have been allocated to speed up research about this rare medical condition. Currently, physicians and researchers from around the world are working to better understand the disease and advance treatment options for patients.