FaCD Online Syndrome Fact Sheet

Last updated: 26 May 2014

Name: Rhabdoid Tumor Predisposition syndrome

Synonym: RTPS type 1 and 2, Familial Posterior Fossa Brain Tumors of Infancy

Mode of Inheritance: AD

Genes

hSNF5/INI1/SMARCB1, mapped to 22q11.2
SMARCA4/BRG1 , mapped to 19p13.2

Tumor features

atypical teratoid/rhabdoid tumor of the CNS
choroid plexus carcinoma
medulloblastoma
myoepithelioma
rhabdoid tumor of the kidney

Tumor features (possible)

meningioma

Comment

In general, approximately 10-15% of renal rhabdoid tumors in young infants are associated with a primary CNS tumor. The rhabdoid predisposition syndrome is characterized by an increased risk for infants to develop renal and extra-renal rhabdoid tumors (including atypical teratoma/rhabdoid of the central nervous system (CNS), a highly malignant tumor[1]) and CNS tumors like medulloblastoma and choroid plexus carcinoma (although revision of the histology of tumors may lead to reclassification as CNS atypical teratoid/rhabdoid tumors[1;2]).[2-4,10,12,13]. Myoepithelioma of the lip has been reported in this disorder[9]. Meningioma has been reported has complication of radiation treatment in these patients[8,9]. The majority of patients have been diagnosed before the age of 2 years.

Germline mutations in the hSNF5/INI1 gene have been observed in this disorder[2-6], including germline mosaicism in parents[4] and de novo mutations[6]. A significant proportion of affected patients appear as a sporadic case in their family. In a series of 115 apparently sporadic cases, germline INI1 mutations were found in 26 patients (35%)[16]. Most of these mutations are de novo (or could be mosaic in the parents)[16]. Penetrance is less than 100%[5,9,16]. There was some evidence for a second locus[11] and, indeed, SMARCA4 has been identified as the second gene involved in the syndrome[14,15]. Germline INI1 mutations have also been associated with schwannomatosis.
The atypical teratoma/rhabdoid of the CNS in two sisters (14 and 26-months-old, respectively) reported by Proust et al.[7] might be due to the rhabdoid predisposition syndrome.

References

[1] Burger PC, Yu IT, Tihan T, Friedman HS, Strother DR, Kepner JL, Duffner PK, Kun LE, Perlman EJ. Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group study. Am J Surg Pathol 1998; 22(9):1083-1092.
[2] Biegel JA, Fogelgren B, Wainwright LM, Zhou JY, Bevan H, Rorke LB. Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Gene Chrom Cancer 2000; 28:31-37.
[3] Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 1999; 59(1):74-79.
[4] Sévenet N, Sheridan E, Amram D, Schneider P, Handgretinger R, Delattre O. Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet 65[5], 1342-1348. 1999.
[5] Taylor MD, Gokgoz N, Andrulis IL, Mainprize TG, Drake JM, Rutka JT. Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene. Am J Hum Genet 2000; 66:1403-1406.
[6] Savla J, Chen TTY, Schneider NR, Timmons CF, Delattre O, Tomlinson GE. Mutations of the hSNF5/INI1 gene in renal rhabdoid tumors with second primary brain tumors. J Natl Cancer Inst 2000; 92(8):648-650.
[7] Proust F, Laquerriere A, Constantin B, Ruchoux MM, Vannier JP, Freger P. Simultaneous presentation of atypical teratoid/rhabdoid tumor in siblings. J Neurooncol 1999; 43(1):63-70.
[8] Ammerlaan AC, Houben MP, Tijssen CC, Wesseling P, Hulsebos TJ. Secondary meningioma in a long-term survivor of atypical teratoid/rhabdoid tumour with a germline INI1 mutation. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2008; .
[9] Ammerlaan AC, Ararou A, Houben MP, Baas F, Tijssen CC, Teepen JL, Wesseling P, Hulsebos TJ. Long-term survival and transmission of INI1-mutation via nonpenetrant males in a family with rhabdoid tumour predisposition syndrome. British journal of cancer 2008; 98(2):474-9.
[10] Janson K, Nedzi LA, David O, Schorin M, Walsh JW, Bhattacharjee M, Pridjian G, Tan L, Judkins AR, Biegel JA. Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation. Pediatric blood & cancer 2006; 47(3):279-84.
[11] Frühwald MC, Hasselblatt M, Wirth S, Köhler G, Schneppenheim R, Subero JI, Siebert R, Kordes U, Jürgens H, Vormoor J. Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome. Pediatric blood & cancer 2006; 47(3):273-8.
[12] Lee HY, Yoon CS, Sevenet N, Rajalingam V, Delattre O, Walford NQ. Rhabdoid tumor of the kidney is a component of the rhabdoid predisposition syndrome. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2002 Jul-Aug; 5(4):395-9.
[13] Harris TJ, Donahue JE, Shur N, Tung GA. Case 168: rhabdoid predisposition syndrome--familial cancer syndromes in children.Radiology. 2011 Apr;259(1):298-302.
[14] Schneppenheim R, Frühwald MC, Gesk S, Hasselblatt M, Jeibmann A, Kordes U, Kreuz M, Leuschner I, Martin Subero JI, Obser T, Oyen F, Vater I, Siebert R. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet. 2010 Feb 12;86(2):279-84.
[15] Hasselblatt M, Gesk S, Oyen F, Rossi S, Viscardi E, Giangaspero F, Giannini C, Judkins AR, Frühwald MC, Obser T, Schneppenheim R, Siebert R, Paulus W. Nonsense Mutation and Inactivation of SMARCA4 (BRG1) in an Atypical Teratoid/Rhabdoid Tumor Showing Retained SMARCB1 (INI1) Expression. Am J Surg Pathol. 2011 Jun;35(6):933-935.
[16] Bourdeaut F, Lequin D, Brugières L, Reynaud S, Dufour C, Doz F, André N, Stephan JL, Pérel Y, Oberlin O, Orbach D, Bergeron C, Rialland X, Fréneaux P, Ranchere D, Figarella-Branger D, Audry G, Puget S, Evans DG, Pinas JC, Capra V, Mosseri V, Coupier I, Gauthier-Villars M, Pierron G, Delattre O. Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. Clin Cancer Res. 2011 Jan 1;17(1):31-8.