Phelan-McDermid syndrome is a rare genetic condition impacting speech, mobility, and cognitive development. It typically occurs due to an alteration in chromosome 22 and is present from birth.
It can be difficult to diagnose Phelan-McDermid syndrome (PMS) due to the variety of potential symptoms it can cause.
The diagnostic process will usually involve a child demonstrating suggestive symptoms and genetic tests confirming a gene alteration. Management of symptoms often requires a diverse team of specialists, and an individual will typically require lifelong assistance.
When discussing Phelan-McDermid syndrome, it is worth noting not to confuse the term PMS with premenstrual syndrome, which is a more familiar condition with the same abbreviation.
This article discusses PMS, including its possible symptoms, potential causes, and life expectancy.
The condition may occur due to a variation in a gene, known as SHANK3, or a loss, or deletion, of a small piece of chromosome 22. The deletion occurs near the end of the long arm, or q arm, of the chromosome at a location known as q13.3. This is why the condition is also known as 22q13.3 deletion syndrome.
PMS is a congenital condition, meaning it is present from birth. Evidence notes that more than 2,200 people worldwide have received a diagnosis of PMS. The Phelan-McDermid Syndrome Foundation states that roughly 75% of people with PMS will also receive a diagnosis of autism.
It would appear to affect males and females in equal numbers, and estimates suggest that it has an occurrence rate of 2.5–10 per million births. However, the prevalence is likely higher due to how difficult it can be to diagnose PMS.
PMS is a rare genetic condition, meaning it arises due to alterations in a person’s genes. Typically, it occurs due to deletions, or other structural rearrangements, that impact the q arm of chromosome 22. This chromosomal region contains many genes that can affect mental and physical development.
Namely, PMS is often the result of a change in the SHANK3 gene. This gene codes for a protein that is abundant in the brain and has a role in the function of synapses. This refers to the connections between nerve cells that enable them to communicate. Some health experts argue that the deletion of SHANK3 is the defining diagnostic criteria of PMS. As such, some doctors
There are four different ways that can cause a person to develop PMS:
- Simple deletion: This is the most common type of PMS and occurs when a person loses a piece of chromosome 22. This type usually occurs at random.
- Ring chromosome: This describes when a loss of genetic material from both the long and short arm of chromosome 22 causes it to form a circular structure. A ring chromosome typically occurs de novo, meaning it presents for the first time in a family member due to a variation in a germ cell.
- Unbalanced translocation: This refers to a type of genetic variation where a part of a chromosome can move to either a separate chromosome or another part of the same chromosome. As it is unbalanced, it can result in the gain or loss of genetic material, which can lead to a chromosomal condition.
- Alteration in the DNA sequence of SHANK3: This change may occur during DNA replication or as a result of environmental factors. It can cause changes to the proteins that the gene produces.
PMS can present with a variety of symptoms. As such, it can be difficult to diagnose PMS, as some features can be subtle and some people may miss them or not perceive them as potential symptoms. Some health experts may categorize them into the following categories:
- severely delayed or absent speech
- hypotonia, which refers to low muscle tone
- global developmental delay, meaning a child may take longer to roll over, sit, and walk
- children are often tall and do not weigh enough for their height
- mild physical features, including a prominent forehead, long eyelashes, full cheeks, flat midface, larger ears, wide or rounded nose, drooping eyelids, and flaky toenails
- displaying autistic-like behaviors, such as difficulty making eye contact, repetition, communication issues, limited interests, and obsessive actions
- persistent mouthing and chewing, which may include teeth grinding or tongue thrusting
- unusual perception of pain
People may display symptoms of PMS in very early childhood, sometimes at birth and within the first 6 months of life. A 2022 study suggests that a majority of individuals with PMS receive a diagnosis between 0–16 years of age, with most receiving a diagnosis around ages 6–8 years.
Health experts advise that people should consider a diagnosis if a child displays suggestive findings that could indicate PMS, such as developmental delays, physical features, or hypotonia.
Often, a doctor is able to establish a diagnosis by assessing the genes of the
- Chromosomal microarray analysis (CMA): This is the most common test for diagnosing PMS. It involves using a small blood sample to detect chromosomal deletions or duplications. However, it cannot reveal if PMS is due to a translocation or a ring chromosome.
- Chromosome structural tests: A doctor may also use fluorescence in situ hybridization (FISH) or conventional chromosome analysis (karyotype) to help detect larger deletions and visualize the structure of the chromosome. These tests can identify translocations and ring chromosomes and can also help determine if a parent carries an alteration in their chromosome 22 that could affect their child.
- Sequencing: This refers to a method of reading the genome to report what genes, and versions of them, are present. This can be either a whole exome sequence (WES), which focuses on genes that produce proteins, or whole genome sequence (WGS), which will read every single gene in the genome. These methods can detect very small alterations, such as those that may occur in the SHANK3 gene.
Currently, there is no one treatment option specifically available for PMS. Instead, treatment focuses on managing the specific symptoms of each individual. Symptoms can vary between those with PMS due to different factors, such as genetics. Some symptoms may only occur in some people with PMS, and may occur during specific stages of life or may be cyclical.
As such, individuals with PMS often require the coordinated efforts of a team of specialists that can include:
- a neurologist
- a pediatrician and primary care physician
- a gastroenterologist
- an endocrinologist
- a psychiatrist
- a speech and language therapist
- occupational and physical therapists
- a nephrologist and urologist
- an immunologist
- an orthopedist
Some common treatment approaches in PMS may include:
- occupational and physical therapy
- behavioral therapy, especially if an individual also has autism spectrum disorder
- anticonvulsants and benzodiazepines for those with seizures and myoclonus
- antipsychotics, electroconvulsive therapy, alpha agonists, or stimulants for psychiatric and attention conditions
- melatonin for sleep disturbances
- fluids and antinausea medications for gastrointestinal distress
A 2022 review notes that life expectancy for an individual with PMS is uncertain and will vary between individuals.
People living with this condition do not typically experience life threatening issues but generally have lifelong complications related to the condition. Adults with PMS may not be able to function independently and may require assistance. This highlights the importance of supportive services to help provide a good quality of life.
Resources for individuals living with PMS include:
PMS is a rare genetic condition that can result in developmental delays and behavioral issues. It typically occurs due to an alteration in chromosome 22, often affecting a gene called SHANK3, which plays a role in neuron communication.
PMS can cause a variety of physical, behavioral, and neurological symptoms, which can vary among individuals. Diagnosis involves genetic testing to detect an alteration in chromosome 22. At present, there is no one treatment option for PMS. Evidence suggests that the condition does not typically lead to life threatening complications, but an individual may not be able to function independently and may require lifelong assistance.