FaCD Online Syndrome Fact Sheet

Last updated: 22 Feb 2011

Name: DICER 1 syndrome

Synonym: incl. Pleuropulmonary Blastoma, Familial ; Cystic Nephroma, Familial

Mode of Inheritance: AD

Genes

DICER1, mapped to 14q31

Tumor features

cystic nephroma
hamartomatous polyps in small intestine
ovarian Sertoli-Leydig cell tumor
pleuropulmonary blastoma
thyroid hyperplasia / goitre

Tumor features (possible)

cervical cancer
colon cancer
eye, medulloepithelioma (dictyoma) of the
medulloblastoma
primitive neuroectodermal tumor (PNET)
rhabdomyosarcoma
seminoma
synovial sarcoma
thyroid adenoma
thyroid cancer, papillary
Wilms' tumor (nephroblastoma)

Non-tumor features (possible)

histiocytosis

Comment

Pleuropulmonary blastoma (PPB) is a rare tumor. It can develop in children, usually before the age of 5 years, and lacks malignant epithelial features which sets it apart from adult-type pleuropulmonary blastoma. Familial cases of childhood PPB, together with cystic nephroma and other childhood tumors or early-onset common malignancies have been reported. Co-existing juvenilie polyps of the small intestine were observed in a few patients. [1-6].

Germline mutations in DICER1 have been reported in familial clustering of pleuropulmonary blastoma[7], familial cystic nephroma and combinations[8]. Through analysis of additional families, DICER1 mutations have been shown to be associated with a broad range of tumors, although most mutation carriers are unaffected and mutation penetrance is therefore assumed to be generally low[9]. DICER1 mutations have also been identified in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors[10]

References

[1] Delahunt B, Thomson KJ, Ferguson AF, Neale TJ, Meffan PJ, Nacey JN. Familial cystic nephroma and pleuropulmonary blastoma. Cancer 1993; 71(4):1338-42.
[2] Boman F, Hill DA, Williams GM, Chauvenet A, Fournet JC, Soglio DB, Messinger Y, Priest JR. Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry. The Journal of pediatrics 2006; 149(6):850-854.
[3] Bal N, Kayaselçuk F, Polat A, Bolat F, Yilmaz Z, Tuncer I. Familial cystic nephroma in two siblings with pleuropulmonary blastoma. Pathology oncology research : POR 2005; 11(1):53-6.
[4] Priest JR, Watterson J, Strong L, Huff V, Woods WG, Byrd RL, Friend SH, Newsham I, Amylon MD, Pappo A, Mahoney DH, Langston C, Heyn R, Kohut G, Freyer DR, Bostrom B, Richardson MS, Barredo J, Dehner LP. Pleuropulmonary blastoma: a marker for familial disease. The Journal of pediatrics 1996; 128(2):220-4.
[5] Bouron-Dal Soglio D, Harvey I, Yazbeck S, Rypens F, Oligny LL, Fournet JC. An association of pleuropulmonary blastoma and cystic nephroma: possible genetic association. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2006 Jan-Feb; 9(1):61-4.
[6] Nur S, Badr R, Sandoval C, Brudniki A, Yeh A. Syndromic presentation of a pleuropulmonary blastoma associated with congenital cystic adenomatoid malformation. A case report. Journal of pediatric surgery 2007; 42(10):1772-5.
[7] Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009 Aug 21;325(5943):965
[8] Bahubeshi A, Bal N, Frio TR, Hamel N, Pouchet C, Yilmaz A, Bouron-Dal Soglio D, Williams GM, Tischkowitz M, Priest JR, Foulkes WD. Germline DICER1 mutations and familial cystic nephroma. J Med Genet. 2010 Dec;47(12):863-6.
[9] Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, Barfoot R, Burke A, Chisholm J, Hewitt M, Jenkinson H, King D, Morland B, Pizer B, Prescott K, Saggar A, Side L, Traunecker H, Vaidya S, Ward P, Futreal PA, Vujanic G, Nicholson AG, Sebire N, Turnbull C, Priest JR, Pritchard-Jones K, Houlston R, Stiller C, Stratton MR, Douglas J, Rahman N. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet. 2011 Jan 25. [Epub ahead of print]
[10] Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O'Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA. 2011 Jan 5;305(1):68-77.
[11] Choong CS, Priest JR, Foulkes WD.Exploring the endocrine manifestations of DICER1 mutations. Trends Mol Med. 2012 Sep;18(9):503-5