What is rhabdoid tumor predisposition syndrome?

Rhabdoid tumor predisposition syndrome (RTPS) is a rare genetic – or hereditary – disease that can already result in highly-aggressive tumors in the brain (called atypical teratoid/rhabdoid tumors) and malignant tumors in other tissue – usually the kidneys – (called malignant rhabdoid tumors) in small children. In addition, it is also possible for other tumors or diseases linked with RTPS to occur.

How is rhabdoid tumor predisposition syndrome diagnosed?

RTPS is a genetic disease; in other words, it is based on mutations – or changes in the genetic material – in certain genes. The genes involved are SMARCB1 and SMARCA4. If a child develops an atypical teratoid/rhabdoid tumor (a very aggressive brain tumor) or a malignant rhabdoid tumor (a malignant tumor in other tissue), one of these two genes should be tested to see whether there are any genetic changes. The diagnosis of RTPS can be confirmed by detecting such a mutation.

Since a hereditary disease is involved, blood-related family members of a person with a proven change in the SMARCB1 or SMARCA4 genes should also undergo genetic testing.

What is the risk of cancer?

The two most common clinical features of RTPS are rhabdoid tumors. These malignant tumors can occur in the brain and are then called “atypical teratoid/rhabdoid tumors” (AT/RT); however, they can also form in other tissues and are then called “malignant rhabdoid tumors” (MRT). MRT are most frequently detected in the kidneys. Most AT/RT and MRT occur by the age of 3, although it is also possible for them to occur even later. Mutations of both genes (SMARCB1 or SMARCA4) can result in AT/RT and MRT developing.

In female patients who are carriers of an SMARCA4 mutation, it is also possible for ovarian cancer (small cell ovarian carcinoma of the hypercalcemic type) to occur during adolescence or adulthood.

In addition, it is also possible for other diseases linked with RTPS to occur, namely the following:

  • Schwannomatosis from an SMARCB1 mutation

  • Plexus carcinoma (a malignant brain tumor) from an SMARCB1 mutation

  • Medulloblastoma (a malignant tumor of the cerebellum) due to a mutation in SMARCB1

  • Multiple meningiomas (usually benign tumors) from an SMARCB1 mutation

  • Nicolaides-Baraitser syndrome from an SMARCB1 mutation

  • Coffin-Siris syndrome from an SMARCB1 or SMARCA4 mutation

  • A malignant peripheral nerve sheath tumor from an SMARCB1 mutation

It is not uncommon for those affected to develop several of the tumors listed above at the same time.

Exact figures for the incidence rate are as yet unknown. Nor has it been determined to date how frequently a genetic change leads to the occurrence of tumors or other diseases. However, it has been possible to observe that the risk of developing atypical teratoid/rhabdoid tumors is considerably lower when there is a mutation in the SMARCA4 gene than when there is a mutation in the SMARCB1 gene.

What causes rhabdoid tumor predisposition syndrom?

Rhabdoid tumor predisposition syndrome is a genetic – or hereditary – disease caused by changes in one of two genes, SMARCB1 or SMARCA4. In carriers of these mutations, the DNA which transmits our genetic information can no longer be correctly “transcribed” and repaired in the body’s cells. As a result, malformations, tumors, and other diseases occur.

Approximately 35% of patients with rhabdoid tumors have inherited the underlying genetic change in one of these two genes from their parents; in these cases, it is inherited as an autosomal dominant disease. It is therefore advisable for all blood-related family members of an affected person to be tested for these genetic changes.

Is there a treatment?

Treatment depends on which disease is present and the existing symptoms.

Depending on the disease, it consists of surgical treatment, possibly combined with chemotherapy and/or radiation therapy.

10-30% of patients are still alive five years after an RT/AT or MRT is diagnosed. The figure is around 33% for patients with ovarian cancer (small cell ovarian carcinoma of the hypercalcemic type).

Please ask the doctor who is treating you whether there are open clinical studies in which you can take part.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

With surveillance measures for early detection, the approach has to do with gene mutation as well. In other words, the goal is to determine whether the genetic change is found in SMARCB1 or SMARCA4. While there are not yet any standardized recommendations, the American Association for Cancer Research suggests the following:

Carriers of a SMARCB1 Mutation

  • MRI of the head every 3 months, from early infancy until 5 years of age

  • Ultrasound of the abdomen and kidneys every 3 months, from early infancy until 5 years of age

Carriers of a SMARCA4 Mutation

  • Ultrasound of the abdomen every 6 months for younger women

  • Prophylactic removal of the ovaries for older women

Self-Care and Support

What should I pay special attention to?

Neurological anomalies may include symptoms of an AT/RT. Sleepiness and vomiting are most common in infants and small children. Older children may have other symptoms as well, such as headaches, paralysis of one side of the body, tilting of the head, double vision, or facial paralysis. You should consult a doctor right away if you observe one or more of these symptoms in your child.

Support Groups and Additional Information

Unfortunately, we are as yet unaware of any existing support groups for patients with rhabdoid tumor predisposition syndrome (RTPS) deficiency. We will add new information as it becomes available.