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

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.