"DICER1 Syndrome" – What Is It?
DICER1 syndrome (also known as “DICER1-Pleuropulmonary blastoma familial tumor predisposition syndrome” or “DICER1-Related Disorders”) is a disease caused by mutations, i.e. changes to the genetic material in the DICER1 gene. This genetic disease is associated with an increased risk of developing lung tumors (pleuropulmonary blastoma), kidney tumors (cystic nephroma), ovarian and thyroid tumors, as well as many other benign and malignant tumors.
How Is "DICER1 Syndrome" Diagnosed?
DICER1 syndrome is caused by a genetic mutation, i.e., a change in the genetic material in the DICER1 gene. Genetic tests can detect this mutation, which can confirm the diagnosis. Such genetic testing should always be carried out if one of the following tumors occurs in a person:
- Pleuropulmonary blastoma (PPB)
- Germline tumors of the ovary (Sertoli-Leydig cell tumor, juvenile granulosa cell tumor, gynandroblastoma)
- Cystic nephroma
- Thyroid tumors not otherwise explained, including multinodular goiter, adenomas, and differentiated thyroid carcinoma
- Medulloepithelioma of the ciliary body (CBME) of the eye
- Embryonal rhabdomyosarcoma (ERMS) of the cervix (Sarcoma botryoides)
- Nasal chondromesenchymal hamartoma (NCMH)
- Pituitary blastoma
- Pineoblastoma
Further Clinical Features
The clinical symptoms vary, and their development depends on age. The following is a list of the diseases that occur as part of DICER1 syndrome in connection with the age of those affected:
| Disease | Affected persons (average age at first diagnosis) |
|---|---|
| Pleuropulmonary blastoma – Type I PPB (cystic) – Type II PPB (cystic/solid) – Type III PPB (solid) – Type Ir PPB (cystic) |
0-24 months (8 months) 12-60 months (31 months) 18-72 months (44 months) any age |
| Germline tumors of the ovary – Sertoli-Leydig cell tumor – Juvenile granulosa cell tumor – Gynandroblastoma |
2-45 years (10-25 years) very young girls or > 10 years seldom teenagers, mostly adults |
| Cystic nephroma | 0-48 months |
| Multinodular goiter | 5-40 years (10-20 years) |
| Medulloepithelioma of the ciliary body | 3-10 years |
| Embryonal rhabdomyosarcoma of the cervix | 4-45 years (10-20 years) |
| Nasal chondromesenchymal hamartoma | 6-18 years |
| Pituitary blastoma | 0-24 months |
| Pineoblastoma | 2-25 years |
Other diseases that have been described in connection with mutations in the DICER1 gene: Differentiated thyroid carcinoma (5-40 years (10-20 years)), Wilms tumor (3-13 years), juvenile hamartous intestinal polyps (0-4 years), anaplastic sarcoma of the kidney (2-20 years), medulloblastoma, embryonal rhabdomyosarcoma of the bladder (<5 years), embryonal rhabdomyosarcoma of the ovary, neuroblastoma (<5 years), congenital phthisis bulbi (birth), primitive neuroectodermal tumor of the cervix
What Is the Risk of Cancer?
Most tumors in families with DICER1 mutations occur before the age of 40; pleuropulmonary blastomas typically happen before the age of 6, and cystic nephroma before the age of 4. It is also known that pleuropulmonary blastoma rarely happens more than once in a family. Other diseases, such as nodular hyperplasia of the thyroid gland or benign lung cysts, on the other hand, occur more frequently in families. No statement can yet be made about the probability of individual cancers occurring.
What Is Known About the Development of "DICER1 Syndrome"?
It is important for the human body that genes are regularly switched off in cells in a targeted manner. One way of specifically silencing a gene is to cut this gene into small pieces. This requires a specific protein, the endoribonuclease DICER1, encoded by the DICER1 gene. If there is a mutation, i.e., a change in the DICER1 gene, the protein endoribonuclease DICER1 is no longer produced correctly and cannot fulfill its function. As a result, switching off certain genes is no longer possible, leading to the development of various tumors.
80% of patients with DICER1 syndrome have inherited the disease from their parents. The inheritance pattern according to which the disease is passed on from parent to child is autosomal dominant. The probability that a child of affected parents will also have DICER1 syndrome is 50%.
The remaining 20% of cases are due to a spontaneous or new mutation, known as a de novo mutation.
Is There Any Form of Treatment Available?
The treatment of DICER1 syndrome must always be based on the tumor disease present in the patient. For some tumors, the patient’s age also plays a decisive role in the choice of therapy. This often consists of initial surgical treatment, radiotherapy, and/or chemotherapy.
Pleuropulmonary blastomas are first surgically removed as completely as possible. This is followed by chemotherapy, the intensity of which depends on the type of PPB. Five years after diagnosis, 89% of patients with type I PPB are still alive, 74% with type II, and 53% with type III. In contrast, type Ir PPB has a survival rate of 100% after five years.
In the case of ovarian tumors (Sertoli-Leydig cell tumor, juvenile granulosa cell tumor, and gynandroblastoma), chemotherapy is sometimes carried out before surgical treatment, depending on the stage of the disease. The prognosis for patients with these tumors is generally very good.
Cystic nephromas usually require surgical treatment. If a kidney is riddled with many cysts, it may be necessary to eradicate it.
Diagnosis of " DICER1 Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of "DICER1 Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
In 2024, the American Association of Cancer Research (AACR) issued the following recommendations for the early detection of DICER1 mutations:
Pleuropulmonary Blastoma
- Clinical examination: shortness of breath, chest pain, fever, weight loss?
- X-ray of the lungs every 6 months (0-8 years), then annually (8-12 years)
- CT of the lungs, if necessary, starting at 3 months of age. If findings are normal, lung CT may be repeated at 2.5 to 3 years of age
- If the mutation is not diagnosed until the age of >12 years, an x-ray or CT scan of the lungs may be considered as a basic diagnostic test.
Tumours of the Thyroid Gland
- Annual clinical examination from the age of 8
- Ultrasound of the thyroid gland:
- From 8 years of age; if findings are normal, repeat ultrasound after 3 years
- In case of new asymmetries and/or nodules in the thyroid gland
- After chemotherapy, consider ultrasound every 5 years after cempletion of chemotherapy
- Functional tests if there is clinical evidence of hyperthyroidism or hypothyroidism
Cystic Nephroma
- Clinical examination: abdominal pain, swelling, blood in the urine?
- Ultrasound of the abdomen every six months (0-8 years), then annually (8-12 years)
- If the mutation is not diagnosed until the age of >12 years, an ultrasound examination of the abdomen can be considered as a basic diagnostic test.
Germline Stromal Tumors
- Clinical examination: premature puberty, absence of menstruation, signs of masculinisation, abdominal or pelvic masses?
- In case of abnormal findings, appropriate imaging or laboratory diagnostics
- Ultrasound of the abdomen and pelvis every 6 months from birth or diagnosis until at least 40 years of age
Embryonal Rhabdomyosarcoma of the Cervix (Sarcoma botryoides)
- Clinical examination: blood in the urine, abnormal vaginal bleeding?
- Cystoscopy or examination of the cervix in case of abnormalities
Medulloepithelioma of the Ciliary Body
- Clinical examination: Abnormalities ofthe eye or eye socket? Visual impairment?
- Annual eye examination at 3-10 years of age, including measurement of visual acuity
Nasal Chondromesenchymal Hamartoma
- Ear, nose and throat (ENT) examination if symptoms include: breathing or feeding difficulties, severe runny nose, nosebleeds, visual problems, middle ear infection
- Nasal endoscopy for ophthalmologic signs of involvement of the eye socket (e.g., eye muscle paralysis, drooping eyelids, downward squinting, sinking of the eyeball into the eye socket)
Pituitary blastoma, pineoblastoma, primary intracranial sarcoma, rare tumours
- Clinical examination: neurological abnormalities, Cushing’s syndrome (hypercortisolism), diabetes insipidus?
- MRI of the head if there are symptoms suggestive of intracranial pressure (headache, fontanel tension, vomiting, impaired consciousness) or other neurological abnormalities such as gaze paralysis, visual disturbances or nystagmus
- MRI of the head if there is evidence of excess cortisol
DICER1 Syndrome – What You Can Do Yourself
You Should Pay Attention to This
Early detection examinations are extremely important for detecting tumors as early as possible. If these are consistently followed up, tumors can usually be detected at an early stage, which usually simplifies treatment and improves the prognosis. If new symptoms occur, you should always consult a doctor for further clarification.
Further Information
Unfortunately, we are not yet aware of any support groups for patients with DICER1 syndrome. As soon as we have new information, we will add it here. However, patients can register for the CPS register at any time or have this done by their doctors.
Any further questions?
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