DICER1 tumour predisposition syndrome

The estimated prevalence is 1/6,099-1/8,416 (Kim et al., 2024).

DICER1 syndrome is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% risk of inheriting the germline pathogenic variant. Prenatal molecular testing is technically possible once the familial pathogenic variant has been identified.

Diagnosis is established by molecular genetic testing for a germline DICER1 pathogenic variant. No biochemical or imaging marker is sufficient on its own to confirm the diagnosis; clinical recognition is based on the characteristic tumour spectrum and family history, which together prompt confirmatory molecular testing. Approximately 15% of individuals with a DICER1-associated PPB are thought to have a de novo germline pathogenic variant, 10% of individuals with a de novo DICER1 pathogenic variant have somatic mosaicism for the variant, which may be missed by routine germline testing.

Main differential diagnoses include, but are not limited to:

• : pneumothorax, pulmonary cysts (usually bilateral and multifocal in adulthood), multinodular goitre and renal tumours overlap with DICER1; characteristic skin lesions (fibrofolliculomas, trichodiscomas, acrochordons) appear in the 2nd-4th decades; FLCN
• (including Cowden syndrome): multinodular goitre and differentiated thyroid carcinoma (papillary and follicular), breast and endometrial cancer, mucocutaneous lesions (trichilemmomas, lipomas, papillomas), vascular anomalies, lung cysts; PTEN
• Rhabdoid tumour predisposition syndrome: small-cell carcinoma of the ovary, hypercalcaemic type (malignant rhabdoid tumour of ovary) and renal rhabdoid tumour, typically in early childhood (age <5 years), distinguishing from ovarian sex cord-stromal tumours in DICER1; SMARCA4, SMARCB1

• Genetic testing establishes the molecular diagnosis and confirms a clinically suspected genetic condition.
• A confirmed molecular diagnosis enables specific and individualised surveillance and clinical management as a prerequisite for targeted medical care, decided by the treating physicians in consultation with the affected individual.
• Once the familial pathogenic variant has been identified, predictive testing of at-risk relatives can be offered to clarify carrier status and inform clinical follow-up.

• Schultz KAP, Stewart DR, Kamihara J, Bauer AJ, Merideth MA, Stratton P, Huryn LA, Harris AK, Doros L, Field A, Carr AG, Dehner LP, Messinger Y, Hill DA. DICER1-Related Tumor Predisposition. 2014 Apr 24 [Updated 2026 Mar 25]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 24761742. Available from:
• Kim J, Haley J, Hatton JN, Mirshahi UL, Rao HS, Ramos MF, et al. A genome-first approach to characterize DICER1 pathogenic variant prevalence, penetrance and cancer, thyroid, and other phenotypes in 2 population-scale cohorts. Genetics in medicine open. 2024;2. doi: 10.1016/j.gimo.2024.101846. PMID: . PMCID: PMC11271802.
• Bakhuizen JJ, Hanson H, van der Tuin K, Lalloo F, Tischkowitz M, Wadt K, et al. Surveillance recommendations for DICER1 pathogenic variant carriers: a report from the SIOPE Host Genome Working Group and CanGene-CanVar Clinical Guideline Working Group. Familial cancer. 2021;20(4):337-348. doi: 10.1007/s10689-021-00264-y. PMID: . PMCID: PMC8484187.
• Nelson AT, Vasta LM, Watson D, Kim J, Harris AK, Best AF, et al. Prevalence of lung cysts in adolescents and adults with a germline DICER1 pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/DICER1 Registry. Thorax. 2024;79(7):644-651. doi: 10.1136/thorax-2023-221024. PMID: . PMCID: PMC11179973.