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 pathogenic SMARCA4 variants than with pathogenic SMARCB1 variants
Rhabdoid Tumor Predisposition – Diagnosis
All patients that exhibit an MRT or AT/RT should undergo a genetic examination to check for the existence of a pathogenic SMARCB1 or SMARCA4 variant. In addition, all biological relatives of a person with a proven pathogenic SMARCB1 or SMARCA4 variant 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 pathogenic SMARCA4 variants 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 of Rhabdoid 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
Below are the recommendations from the AACR 2024 Guidelines.
Carriers of a SMARCB1 variant
- Neurological examination and MRI of skull + spinal cord from diagnosis
- every 4-6 weeks (no less frequently than every 2-3 months) from 0-6 months (for ATRT), alternatively sonography of the skull if MRI is not available
- every 3 months until 5 years (for ATRT)
- every 2-3 years from 10 years (for schwannomas)
- Clinical examination and abdominal ultrasound including kidneys and neck every 3 months to 4 years of age from diagnosis, every 6 months from 5 years of age
- Whole-body MRI every 12 months from diagnosis until >5 years of age, exact end date not specified. If feasible, whole-body MRI every 3 months instead of ultrasound
Carriers of a SMARCA4 variant
- As for carriers of a SMARCB1 variant
- Additional for girls/women: Abdominal + pelvic ultrasound every 6 months from 5 years of age (SSCOHT)
