FaCD Online Syndrome Fact Sheet

Last updated: 29 Jul 2011

Name: Chordoma, Familial Clustering of

Mode of Inheritance: AD

Genes

T/TFT, mapped to 6q27

Tumor features

chordoma

Comment

Familial cases of chrodoma are rare[1-5]. Sacrococcygeal chordoma was reported by Foote et al.[1] in a sib-pair: middle-aged brother and sister (both 52 years old). Stepanek et al.[2] reported on a family with 4 affected relatives (2 men and 2 women) in 2 generations and they suggested autosomal dominant inheritance with reduced penetrance. Chordomas seen in this family occurred in the region of the pituitary gland (diagnosis at age of 20 yrs), nasopharynx (31 and 39 yrs) and sacrum (28 yrs). Dalpra et al.[3] reported on a father and daughter diagnosed with a chordoma of the clivus (at age 8 and 5 years, respectively). Another daughter was diagnosed with an astrocytoma at age 11 years. In general, chorodoma of the clivus is the most common type found in familial clusters[13]

There is evidence for locus heterogeneity.[6-12]. Recently, duplications of a region on 6q27 were observed in four families with multiple chordoma cases. The duplicated region contains only the T (brachyury) gene[13]. This duplication has also been identified as somatic mutation in sporadic chordomas[14].

References

[1] Stepanek J, Cataldo SA, Ebersold MJ, Lindor NM, Jenkins RB, Unni K, Weinshenker BG, Rubenstein RL. Familial chordoma with probable autosomal dominant inheritance. Am J Med Genet 75[3], 335-336. 1998.
[2] Foote RF, Ablin G, Hall W. Chordoma in siblings: case reports. Calif Med 1958; 88(5):383-386.
[3] Dalpra L, Malgara R, Miozzo M, Riva P, Volonte M, Larizza L, Conti AMF. First cytogenetic study of a recurrent familial chordoma of the clivus. Int J Cancer 81[1], 24-30. 1999.
[4] Bhadra AK, Casey AT. Familial chordoma. A report of two cases. The Journal of bone and joint surgery. British volume 2006; 88(5):634-6.
[5] Kerr WA, Allen KL, Haynes DR, Sellars SL. Letter: Familial nasopharyngeal chordoma. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 1975; 49(39):1584.
[6] Kelley MJ, Korczak JF, Shah AA, Allikian KA, Goldstein AM, Parry DM. Genetic linkage and loss of heterozygosity analysis in a family with autosomal dominant chordoma. Proc Am Ass Cancer Res 39, 341. 1998.
[7] Parry DM, Patronas N, Glenn GM, Duffey D, Oldfield E, Tucker MA. Autosomal dominant transmission of chordoma in three successive generations. Am J Hum Genet 1997; 61(4):A77.
[8] Miozzo M, Riva P, Ravicini L, Volonte M, Dalpra L, Tibiletti MG, Cerati M, Pericotti S, Larizza L. Mapping of a tumor suppressor locus to 1p36 in familial and sporadic chordomas. Eur J Hum Genet 1999; 7(1):89.
[9] Miozzo M, Dalpra L, Riva P, Volonta M, Macciardi F, Pericotti S, Tibiletti MG, Cerati M, Rohde K, Larizza L, Fuhrman Conti AM. A tumor suppressor locus in familial and sporadic chordoma maps to 1p36. Int J Cancer 2000; 87(1):68-72.
[10] Riva P, Crosti F, Orzan F, Dalprà L, Mortini P, Parafioriti A, Pollo B, Fuhrman Conti AM, Miozzo M, Larizza L. Mapping of candidate region for chordoma development to 1p36.13 by LOH analysis. International journal of cancer. Journal international du cancer 2003; 107(3):493-7.
[11] Kelley MJ, Korczak JF, Sheridan E, Yang X, Goldstein AM, Parry DM. Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33. American journal of human genetics 2001; 69(2):454-60.
[12] Yang XR, Beerman M, Bergen AW, Parry DM, Sheridan E, Liebsch NJ, Kelley MJ, Chanock S, Goldstein AM. Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs). International journal of cancer. Journal international du cancer 2005; 116(3):487-91.
[13] Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ. T (brachyury) gene duplication confers major susceptibility to familial chordoma.Nat Genet. 2009 Nov;41(11):1176-8.
[14] Presneau N, Shalaby A, Ye H, Pillay N, Halai D, Idowu B, Tirabosco R, Whitwell D, Jacques TS, Kindblom LG, Brüderlein S, Möller P, Leithner A, Liegl B, Amary FM, Athanasou NN, Hogendoorn PC, Mertens F, Szuhai K, Flanagan AM. Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study.J Pathol. 2011 Feb;223(3):327-35.