Rhabdoid Tumor Predisposition – Definition
Rhabdoid tumor predisposition syndrome (RTPS1; OMIM #609322, RTPS2; OMIM #613325) is a rare syndrome that can lead to highly-aggressive, atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system and to malignant rhabdoid tumors (MRT) of other – usually renal – tissues in very young children.
Synonym:
Gene:
SMARCB1 (RTPS1), more rarely SMARCA4 (RTPS2)
Gene products:
SMARCB1 (also INI1 or BAF47), SMARCA4 (also BRG1)
Function:
Part of the SWI/SNF chromatin remodeling complex, which serves to restructure nucleosomes, thereby releasing binding sites for DNA-binding proteins to allow transcription, replication, and DNA repair.
Pattern of inheritance:
Autosomal dominant
Prevalence:
Unknown
Incidence of MRT: 0.6/1 million children (5/1 million in the first year of life; 0.04/1 million at age 10-14)
Incidence of AT/RT: 0.7/1 million children (5.4/1 million in the first year of life)
Genotype-phenotype correlation:
SMARCB1: rhabdoid tumor (usually loss-of-function mutations, LOF), schwannomatosis (missense), multiple meningiomas (missense), Nicolaides–Baraitser syndrome (missense), Coffin–Siris syndrome (missense), malignant peripheral nerve sheath tumor (LOF)
SMARCA4: MRT (LOF), AT/RT (LOF), small cell ovarian carcinoma, hypercalcemic type (LOF), Coffin-Siris syndrome (missense)
Penetrance:
Unknown; lower level of penetrance for AT/RT with SMARCA4 mutations than with SMARCB1 mutations
Rhabdoid Tumor Predisposition – Diagnosis
All patients that exhibit an MRT or AT/RT should undergo a genetic examination to check for the existence of an SMARCB1 or SMARCA4 mutation. In addition, all biological relatives of a person with a proven SMARCB1 or SMARCA4 mutation should be tested.
It is not always easy to demonstrate by histological means, since there is a variable pattern of undifferentiated “small round blue cells” with mesenchymal and epithelial components and classic rhabdoid cells, in some cases the latter may also be lacking.
The loss of the SMARCB1 and SMARCA4 proteins can be proven using immunohistochemical methods, which may help to establish the diagnosis.
Differential Diagnoses
- Epithelioid sarcoma
- Chordomas
- Myoepithelial carcinoma of the soft tissue
- Other brain tumors and solid tumors
Clinical Presentation
| Diseases with RTPS | gene |
|---|---|
|
Rhabdoid tumors
|
Disease-dependent: SMARCB1, SMARCA4 |
| Schwannomatosis | SMARCB1 |
| Plexus carcinoma | SMARCB1 |
| Medulloblastoma | SMARCB1 |
| Multiple meningiomas | SMARCB1 |
| Nicolaides-Baraitser syndrome | SMARCB1 |
| Coffin-Siris syndrome | SMARCB1, SMARCA4 |
| Malignant peripheral nerve sheath tumor | SMARCB1 |
| Small cell ovarian cancer of the hypercalcemic type (SCCOHT) | SMARCA4 |
Most MRT and AT/RT occur by age 3, although it is also possible for them to occur even later. Female patients with SMARCA4 mutations also have an increased risk of developing small cell ovarian carcinoma, hypercalcemic type, but not until adolescence or adulthood.
It is not uncommon for those affected to develop multiple primary tumors.
The prognosis is very poor both for AT/RT and MRT as well as for SCCOHT, with a 5-year survival rate of 10-30% and 33%, respectively.
Special Features of Treatment
The treatment of patients with AT/RT and MRT as part of RTPS is no different from the treatment of patients with sporadic rhabdoid tumors.
Diagnosis ofRhabdoid Tumor Predisposition- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis ofRhabdoid Tumor Predisposition- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
There are no standardized recommendations to date.
The American Association for Cancer Research suggests the following:
For carriers of a truncating SMARCB1 mutation:
- Cranial MRI every three months, from early infancy until 5 years of age
- Abdominal/renal ultrasound every three months, from early infancy until 5 years of age
For female carriers of a truncating SMARCA4 mutation:
- Abdominal ultrasound every 6 months for younger women
- Prophylactic ovariectomy for older women
The European Rhabdoid Registry (EU-RHAB) suggests the following:
For carriers of a truncating SMARCB1 mutation:
0-1 year:
- Cranial and abdominal ultrasound every month
- If the quality is insufficient: MRI every 2-3 months
1-5 years:
- MRI of the CNS and spinal axis (plus whole body if necessary) every 2-3 months
- Abdominal and pelvic ultrasound (or MRI) every 3 months
Rhabdoid Tumor Predisposition – Further Information
Open Clinical Trials/ Registries
- Contact the European Rhabdoid Register: michael.fruehwald@klinikum-augsburg.de
- Link to website of the European Rhabdoid Register (EU-RHAB)
- CPS Registry
Additional Resources
Unfortunately, we are currently not aware of any support groups for patients with Rhabdoid Tumor Predisposition syndrome. New information will be added as soon as it becomes available.
