DICER1 tumour predisposition syndrome
Last update: August 2025
DICER1 tumour predisposition syndrome (ORPHA:284343, OMIM:601200, MONDO:0100216) is a rare genetic disorder that predisposes individuals to develop both benign and malignant tumours, particularly in childhood and early adulthood. Thyroid follicular nodular disease (also known as multinodular goiter) is the most common manifestation of the condition, affecting approximately 75% of women and about 20% of men. Multiple tumours are associated with DICER1 tumour predisposition syndrome, but most individuals develop none or only one tumour type. Tumours associated with DICER1 tumour predisposition syndrome include pleuropulmonary blastoma (a rare lung tumour in children), pineoblastoma (a rare central nervous system tumour), cystic nephroma (a benign kidney tumour that can evolve to a high-grade renal sarcoma), Wilms tumour, ovarian Sertoli-Leydig cell tumours, thyroid cancer and sarcomas at various sites. Many other tumour types have been described in association with DICER1 tumour predisposition syndrome but appear to be rare. Expert-opinion based surveillance measures are recommended upon diagnosis to ensure early detection. Thus, predictive testing can be offered in minors at risk.
DICER1 tumour predisposition syndrome is caused by germline heterozygous pathogenic variants in the DICER1 gene, which plays a key role in regulating gene expression and maintaining normal cell function. The DICER1 protein is essential to produce microRNAs, that are small nucleic acids which control the expression of genes regulating cellular processes such as cell division and growth. When a germline pathogenic variant occurs in this gene, and typically a somatic pathogenic variant on the second allele (second hit), the regulation of cellular processes becomes impaired or disrupted, increasing the risk of abnormal cell growth and tumour formation. Pathogenic variants in DICER1 may be more common in the general population than previously presumed, with current estimates at 1:5,000.
The majority of pathogenic variants in the DICER1 gene are inherited in an autosomal dominant inheritance pattern. Some DICER1 pathogenic variants occur as a de novo event. Carriers of heterozygous pathogenic variants have a 50% risk of transmitting the variant to their children. Family members of individuals diagnosed with DICER1 tumour predisposition syndrome should be offered genetic counselling and eventually testing to determine their own risk – even in minors as recommended surveillance already starts in childhood. Depending on the country there might be options for prenatal testing and preimplantation genetic testing when one of the (future) parents harbours a pathogenic variant in DICER1.
Surveillance is recommended for individuals with DICER1 tumour predisposition syndrome to detect tumours as early as possible (specific recommendations are given below). Surveillance should preferably be performed at specialised centres. Expert recommendations include annual physical examinations to age 40 and age dependent imaging studies focused on DICER1-associated tumour types from birth to age 40. For instance, chest X-rays and low-dose CT scans can detect pleuropulmonary blastoma, while abdominal ultrasounds can be used to screen for kidney and ovarian tumours.
Surveillance recommendations
According to the “Surveillance recommendations for DICER1 pathogenic variant carriers: a report from the SIOPE Host Genome Working Group and CanGene-CanVar Clinical Guideline Working Group” (written by Jette J. Bakhuizen et al. in 2021 and endorsed by ERN GENTURIS), specific recommendations for surveillance in individuals with DICER1 pathogenic variants include at minimum the following:
More information
More information regarding DICER1 tumour predisposition syndrome can be found on:
GeneReviews®- DICER1 tumor predisposition
|
Clinical practice guidelines |
ERN GENTURIS care pathway |
ERN GENTURIS patient journey |
ERN GENTURIS publications |
|
Endorsed by ERN GENTURIS* |
|||
|
Currently unavailable |
Currently unavailable |
Thematic Group 4: Other rare – predominantly malignant – genturis |
* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.
ERN GENTURIS webinars - Thematic group 4: Other rare genturis
A list of healthcare providers with expertise in Thematic Group 4: Other rare - predominantly malignant - genturis can be found here.
A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.