Rhabdoid tumour is a rare and highly aggressive cancer that primarily affects infants and young children, often striking before a child’s second birthday and presenting one of the most challenging diagnoses in paediatric oncology.

Understanding Rhabdoid Tumours

A rhabdoid tumour is a fast-growing cancer that most commonly develops in very young children. These tumours get their name because their cells resemble rhabdomyoblasts, which are cells that normally develop into skeletal muscles before birth. However, despite this resemblance, rhabdoid tumours are not actually muscle tumours. They are unusual growths that can appear in different parts of the body, making them particularly complex to diagnose and treat.^[1]

The disease manifests in three main forms depending on where it develops. When the tumour grows in the kidney, it is called a rhabdoid tumour of the kidney. When it develops in soft tissues or organs outside the brain and kidneys, such as the liver, lungs, or skin, it is referred to as a malignant rhabdoid tumour, where “malignant” means cancerous. When these tumours form in the brain or spinal cord, they are known as atypical teratoid rhabdoid tumours. Approximately half of all brain-based rhabdoid tumours develop in a part of the brain called the cerebellum, which controls movement, balance, and posture, or in the brainstem, which controls breathing and heart rate.^[1]

What makes rhabdoid tumours particularly dangerous is their aggressive nature. They spread quickly throughout the body and are notoriously difficult to treat. The tumours grow rapidly, and symptoms can develop and worsen over just days or weeks. This rapid progression means that early recognition and immediate treatment are critical for the best possible outcomes.^[3]

How Common Are Rhabdoid Tumours?

Rhabdoid tumours are extremely rare. Research suggests that fewer than 1 in every 1 million people will develop this type of cancer. In the United States, there are only about 20 to 25 new cases of malignant rhabdoid tumours diagnosed each year. Because of their rarity, many healthcare facilities may never encounter a case, which is why specialized paediatric cancer centres often serve as referral centres for these patients.^[1][2]

The disease overwhelmingly affects infants and toddlers. The most common age for diagnosis is between 11 and 18 months old, with the average age of diagnosis being 15 months. The condition can even develop before birth, though this is less common. While rhabdoid tumours are most frequently seen in the first three years of life, they can occasionally occur in older children. Cases in adults are exceptionally rare.^[1][2]

What Causes Rhabdoid Tumours?

The development of rhabdoid tumours is linked to changes in specific genes that normally help control cell growth. In about 85 to 95 percent of cases, the disease is caused by mutations in a gene called SMARCB1, which is also known by other names including INI1, SNF5, and BAF47. In rare cases, mutations in another gene called SMARCA4 cause the disease.^[1][5]

These genes are known as tumour suppressor genes, which means they produce proteins that help prevent cells from growing and dividing too rapidly or in an uncontrolled way. When these genes are mutated and stop working properly, cells can multiply without the normal safety checks, leading to tumour formation. The SMARCB1 and SMARCA4 genes are part of protein complexes that regulate gene activity through a process called chromatin remodelling. This process affects how tightly DNA is packaged, which in turn controls which genes are turned on or off during development.^[5]

In most cases, the genetic mutation that causes rhabdoid tumours occurs spontaneously, meaning it happens by chance and is not inherited from parents. However, in some children, the mutated gene is present from birth in all cells of the body, a situation called a germline mutation. For a tumour to actually develop, an additional genetic change must occur that eliminates the remaining healthy copy of the gene. This second change happens only in certain cells and is called a somatic mutation. When both copies of the gene are lost or not functioning, tumour formation becomes much more likely.^[5]

Risk Factors

While most rhabdoid tumours occur without any clear risk factors, some children are at higher risk due to inherited genetic conditions. When a child inherits a mutated SMARCB1 or SMARCA4 gene from a parent, they have a condition called rhabdoid tumour predisposition syndrome. Children with this syndrome have a much higher chance of developing rhabdoid tumours, often at a younger age than children without the inherited mutation.^[5][8]

Children with rhabdoid tumour predisposition syndrome are also at risk of developing multiple tumours at the same time or in sequence. For example, a child might develop tumours in both the brain and kidney. Research shows that between 10 and 15 percent of children with malignant rhabdoid tumours have synchronous or sequential brain tumours. Additionally, individuals with this syndrome may develop other types of tumours, including noncancerous growths called schwannomas that grow on nerve cells. Women with the syndrome face an increased risk of developing a rare type of ovarian cancer later in life.^[5][8]

The majority of children who develop rhabdoid tumours do not have a family history of the condition. Their tumours result from new genetic mutations that happen for unknown reasons. This means that even in families with no previous cases, a child can still develop a rhabdoid tumour. Because some cases do involve inherited mutations, genetic counselling is often recommended for families affected by these tumours to understand the risks for other family members.^[1]

Recognizing the Symptoms

The symptoms of rhabdoid tumours vary greatly depending on where the tumour is growing and how old the child is. Because these tumours grow rapidly, symptoms typically appear suddenly and worsen quickly. In many cases, symptoms begin when the growing tumour starts pressing on surrounding tissues or organs, causing pain or interfering with normal function.^[1][3]

For tumours in the abdomen, particularly those affecting the kidneys, the first sign is often a lump or mass that can be felt through the child’s belly. Parents might notice their infant’s abdomen appears swollen or unusually large. The child may experience abdominal pain, particularly on the side where the tumour is growing. Some children develop blood in their urine, a condition called haematuria. Because infants cannot verbally communicate discomfort, parents might notice increased fussiness, crying, or general irritability as the only signs something is wrong.^[2][1]

When rhabdoid tumours develop in the brain or spinal cord, symptoms are quite different. Affected children commonly experience headaches, particularly first thing in the morning. These headaches may temporarily improve after the child vomits. Nausea and vomiting are frequent complaints, as is unusual sleepiness or a decrease in the child’s normal activity level. Parents might notice their child has lost their balance, has trouble walking, or shows a lack of coordination they didn’t have before. In infants, the head size may increase noticeably because the tumour causes pressure to build up inside the skull.^[1][9]

Depending on the location, other symptoms can include fever, swollen lymph nodes, decreased appetite, weight loss, nerve paralysis affecting the arms or legs, difficulty breathing, and in some cases, lesions visible on the skin. The wide range of possible symptoms reflects the fact that these tumours can develop almost anywhere in the body. Because symptoms develop so quickly and can rapidly become severe, immediate medical attention is essential.^[1][3]

Prevention

Currently, there are no known ways to prevent rhabdoid tumours. Because the genetic mutations that cause most cases occur spontaneously and unpredictably, there are no lifestyle changes, dietary modifications, or environmental factors that have been identified as preventive measures. The disease is not caused by anything parents did or did not do during pregnancy or early childhood.^[1]

For families with a known history of rhabdoid tumour predisposition syndrome, genetic counselling and testing can help identify at-risk individuals. When a child is known to carry a germline mutation in the SMARCB1 or SMARCA4 genes, healthcare providers may recommend closer monitoring to catch any tumours as early as possible. This might include regular imaging studies or physical examinations, though there is no standardized screening protocol. Early detection, while not prevention, can sometimes allow for earlier treatment intervention.^[5]

Research into the genetic causes of rhabdoid tumours continues, with scientists working to understand exactly how these genetic changes lead to cancer formation. This knowledge may eventually lead to strategies for prevention or early intervention, but such approaches are not yet available. The rarity of the disease makes research challenging, but specialized centres continue to gather data and study these tumours to improve future outcomes.^[12]

How Rhabdoid Tumours Affect the Body

Understanding what happens in the body when a rhabdoid tumour develops requires looking at how normal cells are supposed to behave and what goes wrong. In healthy tissue, cells grow, divide, and die in an orderly way controlled by various genes and proteins. The SMARCB1 and SMARCA4 genes produce proteins that are part of larger protein complexes responsible for managing gene activity. These complexes work by changing the structure of chromatin, which is the combination of DNA and proteins that packages genetic information in our cells.^[5]

When chromatin is tightly packed, genes in that region are generally turned off. When it’s loosely packed, genes can be turned on. This chromatin remodelling process is crucial during development, helping cells mature into different types with specific functions. When the SMARCB1 or SMARCA4 genes are mutated, the protein complexes they contribute to cannot work properly. This disrupts normal gene regulation, allowing cells to bypass the usual controls on growth and division.^[5]

The result is rapid, uncontrolled cell growth that forms a tumour. These tumour cells look abnormal under a microscope, appearing large with unusual features. They multiply much faster than normal cells and have lost the ability to respond to signals that would normally tell them to stop growing or to die when damaged. Additionally, rhabdoid tumour cells have a dangerous tendency to spread to other parts of the body through a process called metastasis. They can travel through the bloodstream or lymphatic system to establish new tumours in distant locations.^[3]

When tumours grow in the brain or spinal cord, they cause problems by taking up space inside the skull or spinal canal, both of which cannot expand to accommodate the growing mass. This causes increased pressure on the brain tissue, leading to headaches, vomiting, and changes in consciousness. Tumours in the brain can also directly interfere with specific brain functions depending on their location, causing problems with movement, balance, vision, or other neurological functions. When tumours develop in organs like the kidneys or liver, they disrupt the normal function of those organs and can cause pain, bleeding, or organ failure if left untreated.^[9]