DICER1 syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

DICER1 syndrome is an inherited disorder that increases the risk of a variety of cancerous and noncancerous (benign) tumors, most commonly certain types of tumors that occur in the lungs, kidneys, ovaries, and thyroid (a butterfly-shaped gland in the lower neck). Affected individuals can develop one or more types of tumors, and members of the same family can have different types. However, the risk of tumor formation in individuals with DICER1 syndrome is only moderately increased compared with tumor risk in the general population; most individuals with genetic changes associated with this condition never develop tumors.

People with DICER1 syndrome who develop tumors most commonly develop pleuropulmonary blastoma, which is characterized by tumors that grow in lung tissue or in the outer covering of the lungs (the pleura). These tumors occur in infants and young children and are rare in adults. Pleuropulmonary blastoma is classified as one of three types on the basis of tumor characteristics: in type I, the growths are composed of air-filled pockets called cysts; in type II, the growths contain both cysts and solid tumors (or nodules); and in type III, the growth is a solid tumor that can fill a large portion of the chest. Pleuropulmonary blastoma is considered cancerous, and types II and III can spread (metastasize), often to the brain, liver, or bones. Individuals with pleuropulmonary blastoma may also develop an abnormal accumulation of air in the chest cavity that can lead to the collapse of a lung (pneumothorax).

Cystic nephroma, which involves multiple benign fluid-filled cysts in the kidneys, can also occur; in people with DICER1 syndrome, the cysts develop early in childhood.

DICER1 syndrome is also associated with tumors in the ovaries known as Sertoli-Leydig cell tumors, which typically develop in affected women in their teens or twenties. Some Sertoli-Leydig cell tumors release the male sex hormone testosterone; in these cases, affected women may develop facial hair, a deep voice, and other male characteristics. Some affected women have irregular menstrual cycles. Sertoli-Leydig cell tumors usually do not metastasize.

People with DICER1 syndrome are also at risk of multinodular goiter, which is enlargement of the thyroid gland caused by the growth of multiple fluid-filled or solid tumors (both referred to as nodules). The nodules are generally slow-growing and benign. Despite the growths, the thyroid's function is often normal. Rarely, individuals with DICER1 syndrome develop thyroid cancer (thyroid carcinoma).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

DICER1 syndrome is caused by mutations in the DICER1 gene. This gene provides instructions for making a protein that is involved in the production of molecules called microRNA (miRNA). MicroRNA is a type of RNA, a chemical cousin of DNA, that attaches to a protein's blueprint (a molecule called messenger RNA) and blocks the production of proteins from it. Through this role in regulating the activity (expression) of genes, the Dicer protein is involved in many processes, including cell growth and division (proliferation) and the maturation of cells to take on specialized functions (differentiation).

Most of the gene mutations involved in DICER1 syndrome lead to an abnormally short Dicer protein that is unable to aid in the production of miRNA. Without appropriate regulation by miRNA, genes are likely expressed abnormally, which could cause cells to grow and divide uncontrollably and lead to tumor formation.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

DICER1 syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. It is important to note that people inherit an increased risk of tumors; many people who have mutations in the DICER1 gene do not develop abnormal growths.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

DICER1 syndrome is a rare condition; its prevalence is unknown.

Which doctor should you see?

The suggested department for discussing DICER1 syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for DICER1 syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.