What is DICER1 syndrome?

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 in the genetic material of the DICER1 gene. This genetic disease is associated with an increased risk for the development of lung tumors (pleuropulmonary blastoma), kidney tumors (cystic nephroma), tumors of the ovaries and the thyroid gland as well as many other benign and malignant tumors.

How is DICER1 syndrome diagnosed?

The DICER1 syndrome is caused by a gene mutation, i.e. a change in the genetic material in the DICER1 gene. This mutation can be detected in genetic tests, which can confirm the diagnosis. Such a genetic examination should always be carried out if one of the following tumors occurs in a person:

  • Pleuropulmonary Blastoma (PPB)

  • Ovarian germ strand tumors (Sertoli-Leydig cell tumor, juvenile granulosa cell tumor, gynandroblastoma)

  • Cystic Nephroma

  • Tumors of the thyroid gland incl. goiter multinodosa, adenomas and differentiated thyroid carcinoma not otherwise explained

  • Ciliary body medulloepithelioma (CBME) in the eye

  • Embryonal rhabdomyosarcoma (ERMS) of the cervix (sarcoma botryoides)

  • Nasal chondromesenchymal hamartoma (NCMH)

  • Pituitary blastoma

  • Pineoblastoma

Further Clinical Features

The clinical symptoms are varied and their development depends on age. Below is a list of the diseases that occur as part of a DICER1 syndrome in connection with the age of those affected:

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Disease Affected (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)
each age
Ovarian germ strand tumors
•  Sertoli-Leydig cell tumor
•  Juvenile granulosa cell tumor
•  Gynandroblastoma		 .
2-45 years (10-25 years)
very young girls or> 10 years
rare adolescents, mostly adults
Cystic Nephroma 0-48 months
Goiter multinodosa 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
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Other diseases 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 before the age of 6, and cystic nephromas before the age of 4. It is also known that pleuropulmonary blastoma rarely occurs more than once in a family. Other diseases such as nodular thyroid hyperplasia or benign lung cysts are more common in families. So far, no statement can be made about the probability of the occurrence of individual cancers.

What causes DICER1 syndrome?

It is important for the human body that the genes in the cells are regularly switched off in a targeted manner. One way of specifically shutting down a gene is to cut it into small pieces. This requires a specific protein, the endoribonuclease DICER1, which is encoded by the DICER1 gene. If the DICER1 gene is mutated, the endoribonuclease DICER1 protein is no longer produced correctly and is therefore unable to fulfil its function. This means that it is no longer possible to switch off certain genes, which leads to the development of various tumors.

80% of patients with DICER1 syndrome have inherited the disease from their parents. The inheritance, according to which the disease is passed from the parents to the child, is autosomal dominant. The probability that a child of affected parents also suffers from DICER1 syndrome is 50%.

The remaining 20% of cases are based on a spontaneous or new mutation, which is called a de novo mutation.

Is there a treatment?

The treatment of DICER1 syndrome must always be based on the tumor disease present in the patient. For some tumors, the age of the patient also plays a decisive role in the choice of therapy. This often consists of an initial surgical therapy followed by radiation 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. 5 years after diagnosis, 89% of patients with type I PPB still live, 74% with type II and 53% with type III. Type Ir PPB, on the other hand, has a survival rate of 100% after 5 years.

In the case of tumors of the ovaries (Sertoli-Leydig cell tumor, juvenile granulosa cell tumor and gynandroblastoma), depending on the stage of the disease, chemotherapy is sometimes carried out prior to surgical treatment. The prognosis for patients with these tumors is generally very good.

Cystic nephromas usually have to be treated surgically. If a kidney is interspersed with many cysts, it may be necessary to remove it completely.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

A standardised procedure for early detection of cancer in DICER1 mutations is not yet available, but is recommended by the International PPB Registry:

  • Annual clinical examination

  • Diagnostic imaging or laboratory chemistry depending on the type of tumor, patient age and clinical findings

Pleuropulmonary Blastoma

  • Clinical examination: shortness of breath, chest pain, fever, weight loss?

  • X-ray of the lung every 4-6 months (0-8 years), then annually (8-12 years)

  • CT of the lung initially between 3 and 6 months. If the findings are inconspicuous, the next CT of the lung should be performed at the age of 2.5 to 3 years.

  • If the mutation is only diagnosed at the age of >12 years, an X-ray or CT examination of the lung can be considered as a basic diagnosis.

Tumors of the Thyroid Gland

  • Ultrasound of the thyroid gland:

    • From 8 years of age; if the findings are inconspicuous, repeat ultrasound examination after 3 years.
    • In case of new asymmetries and/or nodes of the thyroid gland
    • After chemotherapy or before starting chemotherapy

  • Functional tests for clinical indications of hyper- or hypofunction of the thyroid gland

Cystic Nephroma

  • Clinical examination: abdominal pain, swelling, blood in the urine?

  • Ultrasound of the abdomen every 6 months (0-8 years), then annually (8-12 years)

  • If the mutation is only diagnosed at the age of >12 years, an ultrasound examination of the abdomen can be considered as a basic diagnosis.

Germ Strand Stroma Tumors

  • Clinical examination: Premature puberty, absence of menstruation, signs of masculinisation, abdominal or pelvic space requirements?

    • In the case of abnormal findings, appropriate imaging or laboratory diagnostics

  • Ultrasound of the abdomen and pelvis every 6-12 months from 8-10 years to at least 40 years of age

Embryonic Rhabdomyosarcoma of the Cervix (Sarcoma Botryoides)

  • Clinical examination: blood in urine, abnormal vaginal bleeding?

  • Bladder endoscopy or examination of the cervix in case of abnormalities

Medulloepithelioma of the Ciliary Body

  • Clinical examination: abnormalities in the eye or eye socket?

  • Ophthalmological examination annually from about 3 years of age and at least until the age of 10, including measurement of visual acuity

Nasal Chondromesenchymal Hamartoma

  • Clinical examination from infancy to adulthood: respiratory or eating disorders, nasal discharge, nosebleeds, vision disorders, middle ear inflammation?

  • Nasal endoscopy for ophthalmological signs of orbital involvement (e.g. paralysis of the eye muscles, drooping of the eyelids, downward strabismus, sinking of the eyeball into the orbital cavity)

Hypophysenblastoma

  • MRI of the head when there are signs of excess cortisol

Pineoblastoma

  • Clinical examination: Neurological abnormalities, Cushing’s syndrome, diabetes insipidus?

  • MRI of the head in case of symptoms indicating intracranial pressure (headache, tense fontanel, vomiting, loss of consciousness) or other neurological abnormalities including paralysis of the eyes, impaired vision or nystagmus

Self-Care and Support

What should I pay special attention to?

In order to detect a tumor disease as early as possible, early detection examinations are extremely important. If these are consistently followed up, tumors can usually be detected at an early stage, which usually simplifies therapy and improves the prognosis. If new symptoms appear, you should always consult a doctor so that further clarification can be made.

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