Atypical teratoid/rhabdoid tumour (ATRT) is a rare and aggressive cancer that begins in the brain or spinal cord, affecting mostly very young children. Though uncommon, this fast-growing tumour requires urgent medical attention and specialized treatment.
What Is Atypical Teratoid/Rhabdoid Tumour?
An atypical teratoid/rhabdoid tumour, often shortened to ATRT or AT/RT, is a highly aggressive cancer of the central nervous system (CNS)—the brain and spinal cord. This tumour grows very quickly and is considered malignant, meaning it is cancerous and can spread to other parts of the nervous system.[1][2]
ATRT is classified as an embryonal tumour, which means it develops from cells that were supposed to stop growing and dividing after a baby is born, but instead continue to multiply abnormally. These are the same types of cells that helped form organs and tissues during development in the womb.[3][5]
The tumour most commonly appears in the cerebellum, the part of the brain responsible for movement, balance, and coordination, or in the brain stem, which controls vital body functions like breathing, heart rate, and the muscles involved in seeing, hearing, walking, and talking. However, ATRT can develop anywhere in the brain or along the spinal cord.[1][10]
The tumour can remain in one location, referred to as localized, or it can spread to multiple areas of the brain, spinal cord, or even beyond, which is called disseminated disease. Because ATRT grows so rapidly, it often spreads through cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord.[2][13]
All ATRTs are classified as grade 4 tumours, the highest and most serious grade, indicating they are fast-growing and require immediate and intensive treatment.[2]
Epidemiology: How Common Is ATRT?
Atypical teratoid/rhabdoid tumour is extremely rare. It represents only 1 to 2 percent of all childhood brain tumours.[1] In the United States, it is estimated that around 470 people are living with this disease, with approximately 73 new cases diagnosed each year. Of those newly diagnosed, only about 4 cases occur in adults, meaning the vast majority of patients are children.[2][6]
ATRT is the most common malignant brain tumour in infants younger than 1 year of age. It accounts for about 20 percent of central nervous system tumours in children under three years old.[9][12] Most patients are younger than two years old at the time of diagnosis, although the tumour can also occur in older children and, rarely, in adults.[2][10]
There is a slightly higher occurrence of ATRT in males compared to females, but the difference is not dramatic.[2]
Because ATRT is so rare and has only been formally recognized as a distinct tumour type since the year 2000, awareness and understanding of the disease are still growing within the medical community.[12]
Causes of ATRT
ATRT is a genetic disease, meaning it is caused by changes in the DNA of certain genes. Specifically, most cases of ATRT are linked to mutations in a gene called SMARCB1 (also known as INI1), and less frequently, in a gene called SMARCA4.[2][6][10]
These genes are known as tumour suppressor genes because they produce proteins that help control when and how often cells grow and divide. When these genes function normally, they signal cells to stop growing when they should. But when SMARCB1 or SMARCA4 is damaged or mutated, the protein they produce doesn’t work properly. This allows cells to grow out of control, leading to the formation of a tumour.[2][6]
In more than 90 percent of ATRT cases, the mutation occurs randomly and spontaneously without any known cause. This means the genetic change happens by chance during a child’s development and is not passed down from parents.[1][13]
However, in some cases, the mutation can be inherited. When this happens, the child may have a condition called rhabdoid tumour predisposition syndrome, which increases the risk of developing multiple tumours—both in the central nervous system and in other parts of the body, such as the kidneys. Approximately one-third of patients with ATRT have an underlying inherited mutation.[10][12]
If the mutation is inherited, other family members may also be at risk. For this reason, genetic counseling is often recommended for families affected by ATRT. This involves meeting with a trained professional to discuss the possibility of inherited disease and whether genetic testing is needed.[10][11]
Researchers have also identified three molecular groups of ATRT based on genetic alterations: AT/RT-TYR, AT/RT-SHH, and AT/RT-MYC. Each group tends to occur in different locations in the central nervous system and is more common in different age groups. For instance, AT/RT-MYC is the most frequent subtype in adults.[2][18]
Risk Factors
The primary risk factor for developing ATRT is age. The tumour most commonly affects children younger than 3 years old, with the highest incidence in infants under 1 year of age.[6][9][10]
A family history of rhabdoid tumours or a known inherited mutation in the SMARCB1 or SMARCA4 gene significantly increases the risk. Children who inherit these mutations from their parents are at much higher risk of developing not only ATRT but also other types of rhabdoid tumours in various parts of the body.[10][11]
Because ATRT is so rare, no other lifestyle, environmental, or behavioral risk factors have been clearly identified. Unlike some cancers in adults, childhood brain tumours like ATRT do not appear to be influenced by factors such as diet, exposure to chemicals, or parental habits.[1][13]
Symptoms of ATRT
The symptoms of ATRT depend on several factors, including the child’s age, the location of the tumour in the brain or spinal cord, and the size of the tumour. Because ATRT is such a fast-growing tumour, symptoms often appear suddenly and worsen quickly, sometimes over just a few days or weeks.[1][2][10]
One of the most common symptoms is a headache, especially one that occurs in the morning and may improve after the child vomits. This type of headache is often a sign of increased pressure inside the skull.[1][6]
Nausea and vomiting are also frequent, typically worse in the morning and improving as the day goes on. These symptoms occur because the tumour can block the normal flow of cerebrospinal fluid, leading to a buildup of fluid in the brain, a condition called hydrocephalus.[1][13]
In infants, hydrocephalus may cause the head to grow larger than normal or the soft spot on the baby’s head, known as the fontanelle, to bulge outward. Parents may notice the baby’s head circumference increasing more rapidly than expected.[1][6]
Children with ATRT often experience unusual tiredness or lethargy, and they may show changes in their activity levels. A previously active child might become unusually sleepy or uninterested in playing.[2][10]
Problems with balance, coordination, and walking are common, especially if the tumour is located in the cerebellum, the part of the brain that controls these functions. A child may appear unsteady, stumble frequently, or have trouble with tasks that require fine motor skills.[1][6]
Other possible symptoms include seizures, changes in behavior or personality, difficulty with vision or hearing, and weakness or numbness in parts of the body. Because these symptoms can resemble those of many other common childhood illnesses, it is important to consult a doctor if they persist or worsen rapidly.[10][11]
Prevention
Currently, there are no known ways to prevent ATRT. Because the genetic mutations that cause this tumour occur randomly in most cases, there are no lifestyle changes, dietary measures, vaccinations, or supplements that can reduce the risk of developing the disease.[1][13]
For families with a known inherited mutation in the SMARCB1 or SMARCA4 genes, genetic counseling and testing can help identify family members who may be at risk. Early detection through regular monitoring and imaging studies may allow for earlier intervention if a tumour does develop, although this does not prevent the tumour itself.[10][11]
Because ATRT is not caused by environmental or behavioral factors, there are no screening programs or preventive measures currently recommended for the general population. Research continues to explore the underlying causes of the disease in hopes of finding future prevention strategies.
Pathophysiology: How ATRT Affects the Body
The pathophysiology of ATRT involves complex changes at the cellular and molecular level that disrupt the normal function of the brain and spinal cord. When the SMARCB1 or SMARCA4 gene is mutated, the protein that normally regulates cell growth is lost or becomes non-functional. Without this regulatory protein, cells in the central nervous system begin to divide and multiply uncontrollably.[2][6]
ATRT develops from several different types of very young, embryonic cells, including rhabdoid, neuroepithelial, epithelial, and mesenchymal cells. These cells are normally present during fetal development but should stop dividing after birth. When they continue to grow abnormally, they form a mass that can be large, bulky, and fast-growing.[2][3][18]
As the tumour grows, it takes up space within the confined area of the skull or spinal column, putting pressure on surrounding brain tissue. This increased pressure can disrupt normal brain function and block the flow of cerebrospinal fluid, leading to hydrocephalus.[1][13]
On imaging scans like magnetic resonance imaging (MRI), ATRTs usually appear as large masses with fluid-filled areas. These masses often show areas of bleeding or dead tissue, and they typically brighten with contrast dye, making them easier to see on scans.[2][18]
Because ATRT is so aggressive, it can spread rapidly through the cerebrospinal fluid to other parts of the brain and spinal cord. This spread, called metastasis, makes the disease more difficult to treat and can lead to additional symptoms depending on where the new tumours form.[2][18]
The loss of normal tumour suppressor function in ATRT cells also leads to changes in how genes are turned on or off, a process called epigenetic regulation. These changes allow cancer cells to grow more aggressively and resist the body’s natural defenses.[12]
Understanding the underlying biology of ATRT is critical for developing new treatments. Researchers are working to identify therapies that can target the specific genetic and molecular changes in ATRT cells, offering hope for more effective treatments in the future.[12]
