Table 1.

Key clinical phenotypes associated with germline DICER1 pathogenic variants

Phenotype and relative frequencyApproximate ages of susceptibility range (peak)Malignant (M) or benign (B)Deaths associated in DICER1-mutated cases
Most frequent phenotypes
  Type I (cystic) PPB0–24 m (8 m)My, if progresses to type II or III
  Type II (cystic/solid) PPB12–60 m (31 m)My, ∼40%
  Type III (solid) PPB18–72 m (44 m)My, ∼60%
  Type Ir (cystic) PPBAny ageB or MNone observed
 Multinodular goitera5–40 y (10–20 y)Bn
 Cystic nephroma0–48 m (undetermined)Bn (see anaplastic sarcoma of kidney below)
 Sertoli–Leydig cell tumor of ovary2–45 y (10–25 y)My, <5% of cases
Moderate frequency phenotypes
 Cervix embryonal rhabdomyosarcoma4–45 y (10–20 y)MNone observed
Rare frequency phenotypes
DTC5–40 y (10–20 y)MNone observed
Wilms tumor3–13 y (undetermined)MNone observed
Juvenile hamartomatous intestinal polyps0–4 y (undetermined)Bn
 Ciliary body medulloepithelioma3–10 y (undetermined)B or MNone observed
 Nasal chondromesenchymal hamartoma6–18 y (undetermined)Bn
 Pituitary blastoma0–24 m (undetermined)Undeterminedy, ∼50%
 Pineoblastoma2–25 y (undetermined)My
Very rare phenotypes
 Anaplastic sarcoma of kidneyEstimated 2–20 yMy
 ERMS bladderEstimated <5 yMNone observed
 ERMS ovaryUndeterminedMNone observed
NeuroblastomaEstimated <5 yMy
Congenital phthisis bulbiBirthBn
Juvenile granulosa cell tumorUndeterminedMNone observed
 GynandroblastomaUndeterminedMNone observed
 Cervix primitive neuroectodermal tumorUndeterminedMNone observed
  • NOTE: The conditions in italic may not be sufficiently associated with DICER1 mutations to warrant testing in the absence of other personal or family history suggestive of DICER1 syndrome.

  • Abbreviations: ERMS, embryonal rhabdomyosarcoma; m, months; y, years (approximate ages of susceptibility range); y, yes; n, no (deaths associated in DICER1-mutated cases).

  • aMultinodular goiter occurring below age 18 years may warrant DICER1 testing, even if occurring in the absence of other syndromic features in the patient or family. Adapted from ref. 25 by permission from Macmillan Publishers Ltd.: Nature Reviews Cancer 14:662–72, copyright 2014.