DICER1 Syndrome - An Overview

Introduction

A genetic condition known as DICER1 syndrome raises the chance of both malignant and noncancerous (benign) tumors. The most prevalent forms of tumors associated with this syndrome are those that affect the thyroid, kidneys, ovaries, and lungs. Tumors can develop in affected persons in one or more forms, and various types can occur in members of the same family. However, compared to the general population, the risk of tumor formation is slightly elevated in those with DICER1 syndrome; the majority of people who have the genetic alterations linked to this disorder never develop tumors.

The most prevalent kind of tumor development in individuals with DICER1 syndrome is pleuropulmonary blastoma, which is characterized by tumors growing in lung tissue or the pleura, the outer layer of the lungs. These tumors are uncommon in adults and mostly affect newborns and young children. Based on the characteristics of the tumor, pleuropulmonary blastoma is classified into one of three types: type I growths are comprised of air-filled pockets known as cysts; type II growths contain both solid tumors (also known as nodules) and cysts, and type III growths are made up of solid tumors that can fill a significant portion of the chest. Pleuropulmonary blastomas of kinds II and III are known to spread (metastasize), commonly to the liver, brain, or bones. These tumors are classified as malignant. People with pleuropulmonary blastoma can develop an abnormal buildup of air in the chest cavity that may lead to pneumothorax or the collapse of a lung.

Multiple benign fluid-filled kidney cysts, known as cystic nephroma, can also arise; in individuals with DICER1 syndrome, the cysts appear early in childhood.

Furthermore, linked to DICER1 syndrome are ovarian malignancies called Sertoli-Leydig cell tumors, which usually affect women in their teens or twenties. Women who have Sertoli-Leydig cell tumors may have facial hair, deep voice, and other masculine traits when the male sex hormone testosterone is released. Menstrual periods are irregular for some women who are affected. Tumors with Sertoli-Leydig cells usually do not spread.

Multinodular goiter, an enlargement of the thyroid gland caused by forming many solid or fluid-filled tumors (both known as nodules), is also a possibility for individuals with DICER1 disease. In general, the nodules develop slowly and are benign. The thyroid's function can often remain normal despite the rise in hormones. Thyroid cancer (thyroid carcinoma) is an uncommon condition in those suffering from DICER1 syndrome.

What Are the Causes of DICER1 Syndrome?

Mutations in the DICER1 gene cause DICER1 syndrome. Instructions for producing the protein involved in the synthesis of molecules known as microRNA (miRNA) are given by this gene. A kind of RNA known as microRNA, a chemical relative of DNA, binds to messenger RNA, the molecule that codes for a protein, and prevents the synthesis of new proteins from it. The Dicer protein is engaged in several processes, including cell growth and division (proliferation) and the maturation of cells to take on specialized activities (differentiation), through its involvement in controlling the activity (expression) of genes.

How Is DICER1 Inherited?

One mutated copy of the gene is enough to generate DICER1 syndrome since the condition is inherited in an autosomal dominant form. Although not many people with DICER1 gene mutations develop abnormal growths, it is crucial to remember that people inherit an elevated risk of malignancies.

What Are the Other Names for DICER1 Syndrome?

• Pleuropulmonary blastoma cancer predisposition syndrome associated with DICER1.

• Dysplasia syndrome and familial tumor of the pleuropulmonary blastoma.

• Pleuropulmonary blastoma family tumor susceptibility syndrome.

What Are the Signs and Symptoms of DICER1 Syndrome?

• Atypical growths in the thyroid, kidneys, lungs, and ovaries (in females) are among the signs and symptoms of DICER1 syndrome.

• The lung lesions may be detected by prenatal ultrasonography, or they may be discovered when a newborn's breathing becomes problematic.

• In the lower region of the neck, thyroid cancers manifest as an asymptomatic "lump" (nodule).

• Because of the increased production of the male hormone testosterone, ovarian tumors cause acne, increased body hair in the face, chest, and abdomen, and irregular periods.

• As brain tumors produce more cortisol, they can cause symptoms including weakness, bruises, and increased weight (Cushing's syndrome).

• A patient's medical history, physical examination, laboratory results, and radiologic assessment may reveal tumors in other body parts.

How Is DICER1 Syndrome Diagnosed?

The following factors may raise suspicions about the diagnosis of DICER1 syndrome:

• The existence of certain tumor forms, such as multinodular goiter, pleuropulmonary blastoma, cystic nephroma, and various ovarian and brain cancers (such as pituitary and pineoblastoma and Sertoli-Leydig cell tumors).

• A person's family history reveals that the other relatives have been diagnosed with the previously stated cancer kinds.

• It is predicted that DICER1 gene mutations would be found in 70 percent of patients with pleuropulmonary blastoma (PPB).

• The children should be directed to an institution that has the experience, knowledge, and resources necessary to thoroughly assess them and determine the best course of action for their treatment if there are any signs that they might be experiencing DICER1 syndrome.

• A physician or genetic counselor will create a pedigree, or multigenerational family tree, noting which members of the family have had certain tumors or cancer, along with the age at which the cancer first appeared.

• The doctor or genetic counselor will advise genetic testing if the pattern of clinical symptoms and/or malignancies points to a DICER1 mutation. To find out if the child has any changes to or deletions (losses) of DICER1 genes, a sample of their blood will be taken. After that, their DNA will be separated and examined.

• The results of DICER1 genetic testing can be very helpful in deciding if further tumor screening should be done in the patient's lifetime and other family members.

How Is DICER1 Syndrome Treated?

The DICER1 condition has no known treatment. Rather, the majority of patients with DICER1 syndrome receive cancer surveillance and screening as part of their medical treatment, which enables doctors to identify cancers at the earliest and most curable stages.

Depending on the location, stage, and nature of the DICER1-associated malignancies, a person's course of treatment may include:

• Surgery to remove the growth or tumor(s).

• Radiotherapy.

• Chemotherapy.

Conclusion

Over the past several years, new cases with unique mutations and presentations have been identified and recorded, expanding the phenotypic range of DICER1 syndrome. As a result, the processes underlying the condition and how it manifests in patients have been fully understood. A combination of fundamental, translational, and clinical research will be needed to successfully cure DICER1 syndrome.