SNP Shot: Genomic Insights

Rhabdoid tumor predisposition syndrome (RTPS) is a condition that significantly increases the likelihood of developing malignant tumors known as rhabdoid tumors. These tumors are highly aggressive and are named "rhabdoid" because their cells resemble rhabdomyoblasts. Rhabdomyoblasts are embryonic cells that normally develop into skeletal muscles, which control movement.

Rhabdoid tumors are uncommon in the general population, typically appearing in the first year of life and rarely after age 4. In individuals with RTPS, these tumors tend to appear earlier, with an average age of onset between 4 and 7 months, and sometimes even before birth. Individuals with RTPS may develop multiple tumors simultaneously (multifocal synchronous tumors), meaning several independent primary tumors occur at the same time. The rhabdoid tumors in RTPS tend to grow and spread more rapidly compared to those in children without the syndrome, often leading to a poor prognosis with survival rarely beyond childhood.

Malignant rhabdoid tumors (MRTs) frequently develop in the cerebellum, the brain region responsible for coordinating movement. Rhabdoid tumors located in the brain and spinal cord (central nervous system) are classified as atypical teratoid/rhabdoid tumors (AT/RTs).

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

Besides rhabdoid tumors, individuals with RTPS can also develop other types of tumors. Some children with RTPS may develop benign schwannomas, which are tumors that grow on nerve cells. Women with RTPS face an elevated risk of developing a rare ovarian cancer known as small cell cancer of the ovary hypercalcemic type (SCCOHT).

Inheritance:

RTPS is typically inherited in an autosomal dominant manner. This means that only one copy of a mutated gene in each cell is enough to increase the risk of developing rhabdoid tumors. Most RTPS cases are caused by mutations in the SMARCB1 gene. These cases often occur in individuals with no family history of the disorder, resulting from a new mutation in the gene during the formation of a parent's egg or sperm cell. This new mutation then becomes present in all of the child's cells. In the majority of known RTPS cases associated with SMARCA4 gene mutations, the affected individual inherits the mutated gene from a parent who carries the gene but has not developed any rhabdoid tumors themselves.