Sunday, January 18, 2009

Rhadoid Tumor Predisposition Syndrome: A recently defined genetic disorder

With all the hullabaloo surrounding the 2007 revision of the World Health Organization Classification of Tumors of the Central Nervous System (4th edition), the fact that the WHO consensus committee also recognized a new genetic syndrome got lost in the mix. Here's the scoop on the new syndrome:

Rhabdoid Tumor Predisposition Syndrome (RTPS) is characterized by a germline mutation in the INI1 gene (chromosome 22q11.2) and manifested by a marked predisposition toward the development of malignant rhabdoid tumors of infancy and early childhood. The atypical teratoid/rhabdoid tumor (AT/RT) is by far the most common CNS malignacy associated with this syndrome. Up to one-third of AT/RTs are thought to arise in the setting of RTPS. Other tumors that have also been reported in association with this syndrome include: medulloblastoma, choroid plexus carcinoma, primitive neuroectodermal tumors (PNETs), and malignant rhabdoid tumor of the kidney. Because of the risks associated with RTPS, it is recommended that the germline status of the INI1 allele be investigated in each new case of AT/RT.

Reference: Brat, Daniel J., et al. "Surgical Neuropathology Update: A Review of Changes Introduced by the WHO Classification of Tumors of the Central Nervous System, 4th edition" in Archives of Pathology and Laboratory Medicine: 2008;132: 993-1007).


Chris said...

But not rhabdoid meningiomas, right?

Also, is there some predisposing susceptibility to mutations in chromosomal arm 22q? It seems that 22q keeps popping up as important in different tumors. Neurofibromatosis and RTPS are just two examples of mutations in this area...are they related somehow?

Brian E. Moore, MD said...

When you mention Neurofibromatosis, you are writing about "Central neurofibromatosis", more commmonly known as Neurofibromatosis type 2 (NF2). It is interesting that chromosome 22q is involved in both NF2 and RTPS. In fact, NF 2 involves a mutation in 22q11-13.1 while RTPS involves mutation of 22q11.2. I don't know that there is any relationship between these two mutations, but it does raise the question of genetic instability in this region of the genome. Hmmm....