Disorder Definitions
  • Tuberous Sclerosis Complex (TSC)
  • Phelan-McDermid Syndrome (PMS)
  • PTEN Hamartoma Tumor Syndrome (PHTS)

What is Tuberous Sclerosis Complex?
Tuberous Sclerosis Complex (also commonly referred to as tuberous sclerosis or TS) is a genetic condition that affects many organs and can cause tumors in the skin, kidney, brain, heart, eyes, lungs and other organs. The severity of TSC can range from mild, such as skin abnormalities, to severe, such as seizures, mental retardation or renal failure. The most common symptoms of TSC are seizures and developmental delay, as well as benign tumors and lesions which can affect virtually every organ system of the body including the brain, kidneys, heart, lungs, eyes, skin, and other organs. In many instances, symptoms of TSC will be apparent in the first six months of life.

Who gets Tuberous Sclerosis Complex?
TSC affects approximately 50,000 people in the United States and one million worldwide, with an estimated incidence of 1 in 6,000 live births.

What causes Tuberous Sclerosis Complex?
TSC is caused by a mutation (gene change) in one of two genes: TSC1 and TSC2. Genetic testing for TSC at this time is able to detect mutations in the TSC1 or TSC2 genes in approximately 80% of individuals. For the other 20% of individuals without an identifiable mutation, researchers are studying ways to accurately find mutations in these two known genes and look for additional genes that may be involved.

How is Tuberous Sclerosis Complex diagnosed?
Clinical diagnosis of TSC is based on a careful physician exam in combination with imaging of the brain, heart and kidneys. The physician will carefully examine the skin for the wide variety of skin lesions, often using an ultraviolet light called a Wood’s lamp which may be useful for finding skin features that can be hard to see on infants or individuals with pale skin.

There is no single clinical feature absolutely specific to the condition. In addition, many features of TSC, such as seizures and developmental delay, are seen in individuals without TSC. Therefore, a constellation of features is necessary for the diagnosis and an increasing number of features make the clinical suspicion of TSC more likely.

Recently, genetic testing for TSC has become more readily available, and a positive genetic test can be considered diagnostic.

What is the treatment for Tuberous Sclerosis Complex?
While, unfortunately, there is no cure for TSC yet, effective treatments are available for a variety of the symptoms. Drugs to prevent seizures are accessible to individuals and surgery can often correct skin abnormalities. Surgery to remove tumors can help to preserve the function of affected organs. For other symptoms of TSC, such as developmental delay, services such as early intervention, special education and other therapies are often effective in moderating symptoms.

Frequently Asked Questions

In general, one third of individuals with TSC inherit the genetic condition from a parent. Two thirds of all cases are sporadic (occur for the first time in a family).

TSC is inherited as an autosomal dominant genetic condition. This means that a mutation in only one copy of the gene causes the condition. Individuals with TSC have a 50% chance of passing their condition to each of their children.

The prognosis of individuals with TSC varies from individual to individual. The severity of the complications determines the long term outlook, and symptoms can range from mild to extremely severe. Most individuals who are mildly affected with TSC and are under an experienced physician’s care can expect to live active and productive lives with normal life expectancy.
In some people, certain symptoms associated with TSC become less severe over time. Individuals with TSC are monitored by their doctors yearly for any changes.
TSC is a genetic disorder and is not caused by an allergy.
TSC is a genetic disorder and is not caused by an injury.
TSC can affect many different organs in the body. Individuals with TSC should be carefully monitored by their physicians for any changes in their symptoms.

What is Phelan-McDermid Syndrome?
Phelan-McDermid Syndrome (PMS), also known as 22q13.3 deletion syndrome, is caused by a loss of a piece of chromosome 22 near the end of the chromosome at a location designated q13.3. The symptoms of PMS can vary from person to person but it is typically characterized by low muscle tone, global developmental delay/intellectual disability, motor skills delay, delayed or absent speech and autism spectrum disorder.

Who gets Phelan-McDermid Syndrome?
There are over 500 cases of PMS. The exact incidence is unknown.

What causes Phelan-McDermid Syndrome?
PMS is caused by a deletion near the long arm of chromosome 22. The chromosomal region that is typically deleted contains the SHANK3 gene. As a result, people with PMS have only one copy of the SHANK3 gene in each cell rather than two copies. The SHANK3 gene provides instructions for making protein that is found in many organs. It is especially important for brain functioning and development as the protein is most abundantly found there. Thus it is thought that a reduction in the amount of SHANK3 protein caused by a loss of the SHANK3 gene is responsible for many features associated with PMS.

How is Phelan-McDermid Syndrome diagnosed?
There are no clinical diagnostic criteria for PMS. PMS is diagnosed through genetic testing, such as high resolution chromosome analysis and fluorescence in situ hybridization or more commonly, chromosomal microarray.

Most instances of PMS are a result of de novo chromosomal abnormality. This means that the deletion happened randomly during fetal development. In a few cases 22q13.3 can be inherited. Parental chromosome analysis and prenatal testing are possible options.

What is the treatment for Phelan-McDermid Syndrome?
Effective treatments are available for a variety of the symptoms that occur with PMS. Medications for seizure management, behavioral interventions, medications for anxiety and hyperactivity as well as physical and occupational therapy and speech and communication therapy are all available treatments for moderating PMS symptoms.

Frequent follow up with care providers, including brain imaging and renal ultrasounds to detect changes and abnormalities is recommended.

Frequently Asked Questions

Phelan-McDermid Syndrome is caused by a loss of a small piece of chromosome 22. The deletion happens during the formation of reproductive cells or in early fetal development. This occurs randomly during these processes. Less commonly, people with PMS can pass on the chromosomal deletion to their children.
The prognosis of individuals with PMS varies from individual to individual. The severity of the complications determines the long term outlook, and symptoms can range from moderate to extremely severe.
Individuals with PMS are monitored by their doctors regularly for any changes.
PMS is a genetic disorder and is not caused by an allergy.
PMS is a genetic disorder and is not caused by an injury.
PMS can affect many different organs in the body. Individuals with PMS should be carefully monitored by their physicians for any changes in their symptoms.

What is PTEN Hamartoma Tumor Syndrome?

PTEN Hamartoma Tumor Syndrome refers to a group of conditions caused by an alteration in the PTEN gene. Clinically, it includes Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome and ASD. Patients with PTEN mutations typically develop benign growths in different organs of their body as well as experience skin lesions, developmental delay, cognitive abnormalities, macrocephaly (enlarged head size) and autism spectrum disorder. Individuals with PTEN mutations may develop some or all of these symptoms in varying degrees of severity. Individuals with PTEN mutations are also at a higher risk for developing some forms of cancer.

Who gets PTEN Hamartoma Tumor Syndrome?
PHTS is a rare disorder. The exact incidence is unknown.

What causes PTEN Hamartoma Tumor Syndrome?
PHTS is caused by a change (mutation) in the PTEN gene. PTEN is a gene that helps control cell growth. When mutated, cells grow out of control and accumulate leading to the formation of tumors.

How is PTEN Hamartoma Tumor Syndrome diagnosed?
PHTS may be suspected based on a number of clinical features. A definitive diagnosis of PHTS is made only when a mutation in the gene is found through genetic testing.

What is the treatment for PTEN Hamartoma Tumor Syndrome?
Effective treatments are available for management of manifestations. Frequent surveillance for tumor detection and management is recommended. Other treatments, such as behavioral interventions, are also available.

Frequently Asked Questions

PTEN hamartoma tumor syndrome is cause by a mutation in the PTEN gene. PHTS can be inherited from a parent who has a mutated copy of the PTEN gene, or it can result during a random event during reproduction or in the cell of a developing fetus. In the latter case, these individuals will be the first in their family to carry an altered gene.
Individuals with PHTS need to be frequently monitored by their physicians for any changes in their symptoms.
In some people, certain symptoms associated with PHTS may become less severe over time. Individuals with PHTS need to be monitored by their doctors for any changes.
PHTS is caused by a genetic mutation and is not caused by an allergy.
PHTS is caused by a genetic mutation and is not caused by an injury.
PHTS can affect many different organs in the body. Individuals with PHTS should be carefully monitored by their physicians for any changes in their symptoms.

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