Rhabdoid tumor predisposition syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Rhabdoid tumor predisposition syndrome (RTPS) is characterized by a high risk of developing cancerous (malignant) growths called rhabdoid tumors. These highly aggressive tumors are called rhabdoid because their cells resemble rhabdomyoblasts, which are cells that are normally found in embryos before birth and develop into muscles used for movement (skeletal muscles).

Rhabdoid tumors are rare in the general population. They usually occur in the first year of life, and are much less likely to appear after age 4. In people with RTPS, the tumors occur at an average age of 4 to 7 months, and can even occur before birth. Affected individuals may have multifocal synchronous tumors, which means that multiple tumors that develop independently (primary tumors) occur at the same time. The rhabdoid tumors that occur in RTPS usually grow and spread more quickly than those in children without this predisposition, and affected individuals often do not survive past childhood.

More than half of all malignant rhabdoid tumors (MRTs) develop in the cerebellum, which is the part of the brain that coordinates movement. Rhabdoid tumors in the brain and spinal cord (central nervous system) are called atypical teratoid/rhabdoid tumors (AT/RTs).

Rhabdoid tumors also occur outside the central nervous system. These tumors include rhabdoid tumors of the kidneys (RTKs) and tumors that develop in other organs and tissues of the body (called extrarenal malignant rhabdoid tumors or eMRTs). The type of rhabdoid tumor can vary among individuals with RTPS, even within the same family.

Tumors other than rhabdoid tumors can also occur in people with RTPS. Some affected children develop noncancerous (benign) tumors called schwannomas, which grow on nerve cells. Women with RTPS are at increased risk of developing a rare type of ovarian cancer called small cell cancer of the ovary hypercalcemic type (SCCOHT).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

In 85 to 95 percent of affected individuals, RTPS is caused by mutations in the SMARCB1 gene. These cases are sometimes known as RTPS1. A small number of cases (called RTPS2) are caused by mutations in the SMARCA4 gene. These genes provide instructions for making proteins that form pieces (subunits) of several different protein groups called SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed.

Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells. Through these processes, the proteins produced from the SMARCB1 and SMARCA4 genes, as well as other SWI/SNF subunits, are thought to act as tumor suppressors, which keep cells from growing and dividing too rapidly or in an uncontrolled way.

RTPS is caused by a mutation in the SMARCB1 or SMARCA4 gene that is present in cells throughout the body (called a germline mutation). An additional genetic change that deletes the normal copy of the gene is needed for a tumor to develop. This additional change is acquired during a person's lifetime and is present only in the cancerous cells. Such changes are known as somatic mutations. In combination, the germline and somatic mutations lead to the absence or dysfunction of the protein produced from the SMARCB1 or SMARCA4 gene. This deficiency likely impairs the tumor suppressor function of the proteins, but the specific mechanism that leads to rhabdoid tumors is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to predispose the affected individual to rhabdoid tumors.

The majority of cases of RTPS are caused by SMARCB1 gene mutations. These cases usually occur in people with no history of the disorder in their family. They result from a new mutation in the gene that occurs in a parent's egg or sperm cell and is found in all the child's cells.

In most known cases of RTPS caused by SMARCA4 gene mutations, an affected person inherits the mutation from one parent who has the altered gene but has not developed any rhabdoid tumors.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

In the United States, rhabdoid tumors occur in about 1 per million children under age 15. RTPS is thought to account for between a quarter and a third of these tumors.

Which doctor should you see?

The suggested department for discussing Rhabdoid tumor predisposition syndrome is Oncology, with a oncologist and relevant organ specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics; Relevant organ specialist / Surgical Oncology as indicated.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Has the exact tumour type been confirmed, and is staging relevant?
• What is the goal of each proposed treatment option?
• How will side effects, daily function and supportive care be addressed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Rhabdoid tumor predisposition syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.