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Familial Cancer
Published in: Familial Cancer 1/2016

01-01-2016 | Original Article

Incidental diagnosis of HLRCC following investigation for Asperger Syndrome: actionable and actioned

Authors: Bich-Thu Duong, Ravi Savarirayan, Ingrid Winship

Published in: Familial Cancer | Issue 1/2016

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Abstract

Incidental findings are inevitable as clinical research and practice transitions from a single gene approach to a genomic approach. A novel deletion of the Fumarate Hydratase (FH) gene was identified in a 22 year old male who underwent a molecular karyotype as part of an autism spectrum disorder research project. This unexpected result implies a predisposition to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), a rare, autosomal dominant condition and has unforeseen implications for him and his family. We review the typical features and management of HLRCC and discuss the challenges that face health professionals, as genetic testing advances and becomes more accessible.
Literature
1.
Law R, Dixon-Salazar T, Jerber J et al (2014) Biallelic truncating mutations in FMN2, encoding the actin-regulatory protein formin 2, cause nonsyndromic autosomal-recessive intellectual disability. Am J Hum Genet 95:721–728PubMedPubMedCentralCrossRef
2.
Kiuru M, Launonen V (2004) Hereditary leiomyomatosis and renal cell cancer (HLRCC). Curr Mol Med 4:869–875PubMedCrossRef
3.
Isaacs JS, Yun JJ, Mole DR et al (2005) HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 8:143–153PubMedCrossRef
4.
Mroch A, Laudenschlager M, Flanagan J (2012) Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency. Am J Med Genet 158A:155–158PubMedCrossRef
5.
Menko FH, Maher ER, Schmidt LS et al (2014) Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment. Fam Cancer 13(4):637–644PubMedPubMedCentralCrossRef
6.
Lehtonen HJ (2011) Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics. Fam Cancer 10:397–411PubMedCrossRef
7.
Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT (2011) LOVD v. 2.0: the next generation in gene variant databases. Hum Mutat 32(5):557–563PubMedCrossRef
8.
Alam N, Rowan A, Worth N et al (2003) Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. Hum Mol Genet 12:1241–1252PubMedCrossRef
9.
Pavlovich C, Schmidt L (2004) Searching for the hereditary causes of renal-cell carcinoma. Nat Rev Cancer 4:381–393PubMedCrossRef
10.
Toro JR, Nickerson ML, Wei MH et al (2003) Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet 73:95–106PubMedPubMedCentralCrossRef
11.
Merino MJ, Torres-Cabala C, Pinto P et al (2007) The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol 31:1578–1585PubMedCrossRef
12.
van Spaendonck-Zwarts K, Badeloe S, Oosting S et al (2012) Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance. Fam Cancer 11:123–129PubMedPubMedCentralCrossRef
13.
Iliopoulos O, Eng C (2000) Genetic and clinical aspects of familial renal neoplasms. Semin Oncol 27:138–149PubMed
14.
Berg JS, Khoury MJ, Evans JP (2011) Deploying whole genome sequencing in clinical practice and public health: meeting the challenge one bin at a time. Genet Med 13:499–504PubMedCrossRef
15.
Green RC, Berg JS, Grody WW et al (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 15(7):565–574PubMedPubMedCentralCrossRef
16.
17.
Burke W, Antommaria AHM, Bennett R et al (2013) Recommendations for returning genomic incidental findings? We need to talk! Genet Med 15(11):854–859PubMedCrossRef
18.
van El C, Cornel M, Borry P (2013) Whole-genome sequencing in health care. Recommendations of the European society of human genetics. Eur J Hum Genet 21:580–584PubMedPubMedCentral
19.
Lemke AA, Bick D, Dimmock D et al (2013) Perspective of clinical genetics professionals toward genome sequencing and incidental findings: a survey study. Clin Genet 84:230–236PubMedPubMedCentralCrossRef
20.
Strong KA, Zusevics KL, Bick D et al (2014) Views of primary care providers regarding the return of genome sequencing incidental findings. Clin Genet 86(5):461–468PubMedCrossRef
Metadata
Title
Incidental diagnosis of HLRCC following investigation for Asperger Syndrome: actionable and actioned
Authors
Bich-Thu Duong
Ravi Savarirayan
Ingrid Winship
Publication date
01-01-2016
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 1/2016
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-015-9829-5

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