DICER1 pleuropulmonary blastoma familial tumour predisposition syndrome: What the paediatric urologist needs to know

Summary Introduction Germline-inactivating DICER1 mutations are responsible of a familial tumour susceptibility syndrome with an increased risk of tumours, mainly pleuropulmonary blastoma (PPB). DICER1 mutations also cause a range of other tumours, some of them in urogenital organs (cystic nephroma...

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Bibliographic Details
Published in:Journal of pediatric urology 2016-02, Vol.12 (1), p.5-10
Main Authors: Faure, Alice, Atkinson, John, Bouty, Aurore, O'Brien, Mike, Levard, Guillaume, Hutson, John, Heloury, Yves
Format: Article
Language:English
Subjects:
Cystic nephroma
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - metabolism
DICER1
DNA, Neoplasm - genetics
Embryonal rhabdomyosarcoma
Genetic Predisposition to Disease
Germ cell tumours
Humans
Mutation
Ovarian sex cord-stromal tumours
Pediatrics
Phenotype
Pulmonary Blastoma - genetics
Pulmonary Blastoma - metabolism
Ribonuclease III - genetics
Ribonuclease III - metabolism
Syndrome
Urology
Wilms
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Summary:Summary Introduction Germline-inactivating DICER1 mutations are responsible of a familial tumour susceptibility syndrome with an increased risk of tumours, mainly pleuropulmonary blastoma (PPB). DICER1 mutations also cause a range of other tumours, some of them in urogenital organs (cystic nephroma [CN], ovarian sex cord-stromal tumours, bladder and cervix embryonal rhabdomyosarcoma [ERMS]). Objective The aim was to clarify the range of urogenital phenotypes associated with DICER1 mutations and to give practical course of action to paediatric urologist that are exposed to DICER1 -related conditions. Study design A literature review was performed. Pertinent papers focused on urogenital diseases associated with DICER1 mutations were reviewed. Results Seventy per cent of CN have a DICER1 germline mutation. The majority of them (80%) have PPB. Like PPB, CN could undergo a malignant progression to a primitive sarcoma. Some rare cases of Wilms tumours were reported. Regarding gonadal manifestations, sex-cord stromal neoplasia of the ovary, especially Sertoli–Leydig cell tumour (SLCT), is the most frequent tumour associated with DICER1 germline mutation. Germline DICER1 mutations also predispose to uterine cervix and bladder ERMS. Discussion The presence of unusual tumours suggesting DICER1 mutations may alert clinicians. The first step is to obtain a complete familial history. The variable clinical presentation and the modest penetrance raise concerns about the appropriateness of genetic testing to patients and their relatives. The education of DICER1 mutations carriers about tumour-related symptoms is consensual. In the first 5 years of life, a yearly chest X-ray and abdominal ultrasound are recommended. Conclusion The presence of a CN, ovarian SLCT or urogenital ERMS in a child should alert the clinician to the possibility of DICER1 mutation and the associated risk of PPB. Individuals with one of the typical DICER1 conditions should be offered DICER1 analysis. Despite the low penetrance, a genetic counselling and testing should be offered to the family of the affected child.
ISSN:1477-5131
1873-4898
DOI:10.1016/j.jpurol.2015.08.012