DICER1 syndrome

DICER1 Syndrome: A Rare Genetic Disorder

DICER1 syndrome is a rare genetic disorder that increases the risk of developing various types of tumors, both benign and malignant [4]. It is caused by faults (mutations) in the DICER1 gene, which affects the body's ability to regulate cell growth and division [5].

Increased Risk of Tumors

People with DICER1 syndrome have an increased chance of developing early childhood lung cancer, as well as other types of tumors in various parts of the body, including the kidneys, thyroid, and ovaries (in females) [2]. The lung lesions may be identified on prenatal ultrasounds, making it a condition that can be detected before birth [2].

Genetic Basis

DICER1 syndrome is an autosomal dominant disorder, meaning that only one copy of the mutated gene is needed to increase the risk of developing tumors. It is caused by variants in the DICER1 gene, which codes for an enzyme involved in the regulation of cell growth and division [3][7].

Diagnosis

The diagnosis of DICER1 syndrome is suspected based on clinical findings, such as abnormal growths or tumors in various parts of the body. This should be confirmed by a genetic test to study a mutation in the DICER1 gene [8].

References:

• [1] May 1, 2016 — DICER1 syndrome is an inherited disorder that increases the risk of a variety of cancerous and noncancerous (benign) tumors, most commonly ...
• [2] Symptoms of DICER1 syndrome include abnormal growths in the lungs, kidneys, thyroid and ovaries (for females). The lung lesions may be identified on prenatal ...
• [3] by AM Caroleo · 2020 · Cited by 59 — DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene.
• [4] DICER1 syndrome is a rare disorder that makes a person more likely to develop certain types of tumors, both benign and malignant.
• [5] DICER1 syndrome is caused by faults (mutations) in the DICER1 gene. People with a faulty DICER1 gene have an increased chance of developing early childhood lung ...
• [6] by C Spinelli · 2023 · Cited by 2 — Simple Summary. DICER1 syndrome is a rare genetic disorder that predisposes patients to the development of malignant and non-malignant diseases.
• [7] by IA González · 2022 · Cited by 96 — DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 ...
• [8] The diagnosis of DICER1 syndrome is suspected based on clinical findings. This should be confirmed by a genetic test, to study a mutation in the gene DICER1.
• [9] by AM Caroleo · 2021 · Cited by 59 — DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene.

DICER1 Syndrome: Signs and Symptoms

DICER1 syndrome is a rare inherited disorder that increases the risk of developing various types of tumors, most commonly in the lungs, kidneys, thyroid, and ovaries (for females) [2]. The symptoms of DICER1 syndrome can vary widely among affected individuals, even within the same family [8].

Common Signs and Symptoms:

• Abnormal growths in the lungs, kidneys, thyroid, and ovaries (for females)
• Unexplained weight loss
• Loss of appetite
• General signs and symptoms that could signal cancer

It's essential for people with DICER1 syndrome to watch closely for these general signs and symptoms [3]. Early detection and diagnosis are crucial for effective management and treatment.

Specific Symptoms:

• The most frequent abnormality in DICER1 syndrome is the development of multiple benign lumps (nodules and cysts) scattered throughout the gland [6].
• Pleuropulmonary blastoma (PPB), pulmonary cysts, thyroid gland abnormalities, and other types of tumors may also occur.

Genetic Cause:

DICER1 syndrome is caused by faults (mutations) in the DICER1 gene. People with a faulty DICER1 gene have an increased chance of developing early childhood lung cancer and other types of tumors [4].

References: [2] May 1, 2016 — [3] Problems to watch for​​ [4] DICER1 syndrome is caused by faults (mutations) in the DICER1 gene. [6] The most frequent abnormality in DICER1 syndrome is the development of multiple benign lumps (nodules and cysts) scattered throughout the gland. [8] The severity and specific symptoms of DICER1 syndrome can vary widely among affected individuals, even within the same family.

Diagnostic Testing for DICER1 Syndrome

DICER1 syndrome can be diagnosed through various diagnostic tests, which are crucial in identifying the genetic basis of the condition and informing prognosis.

• Genetic testing: This is the primary method for diagnosing DICER1 syndrome. Targeted next-generation sequencing (NGS) is used to evaluate somatic mutations within the DICER1 gene [2]. Genetic testing can be performed on blood, saliva, or tumor tissue in patients with a known or suspected DICER1 syndrome condition [3].
• Single-gene sequencing: This test evaluates for changes in the DICER1 gene and can inform prognosis [4].
• Multigene panel testing: This type of testing considers multiple genes, including DICER1, to identify potential genetic causes of conditions [5].
• Exome sequencing: This comprehensive test examines all protein-coding regions of the genome, which may be useful in identifying rare or novel mutations [6].

Surveillance and Monitoring

In individuals with confirmed DICER1 syndrome, clinical examination and imaging-based surveillance are recommended to monitor for signs and symptoms of associated tumors, such as:

• Pulmonary Pleuro-pulmonary blastoma (PPB)
• Thyroid gland neoplasia
• Ovarian sex cord-stromal tumors

Regular monitoring can help identify potential complications early on, allowing for timely intervention [7].

Family Variant Testing

For individuals diagnosed with a pathogenic germline variant in DICER1, family variant testing is recommended to identify at-risk relatives. This involves sequencing the DICER1 gene in blood relatives of affected individuals [8].

References:

[2] Jul 11, 2023 — Targeted next-generation sequencing for somatic mutations within the DICER1 gene.

[3] Ordering instructions for DICER1 mutation testing on blood, saliva or tumor tissue in patients with a known or suspected DICER1 syndrome condition.

[4] Consideration should be given to a single, baseline abdominal ultrasound in individuals who are diagnosed with a pathogenic germline variant in DICER1 after ...

[5] We offer family variant testing for all blood relatives of patients who undergo full single gene sequencing, multigene panel testing or exome sequencing at ...

[7] In individuals with confirmed DICER1, clinical examination and imaging-based surveillance for signs and symptoms of PPB, thyroid gland neoplasia, ovarian sex cord-stromal tumors, and other DICER1-associated tumors is recommended.

[8] We offer family variant testing for all blood relatives of patients who undergo full single gene sequencing, multigene panel testing or exome sequencing at ...

Current Drug Treatments for DICER1 Syndrome

While there is no specific treatment for DICER1 syndrome, various drug treatments have been explored to manage its symptoms and associated conditions.

• Chemotherapy: Chemotherapy has been used as a primary treatment modality for some cases of DICER1 syndrome, particularly for pleuropulmonary blastoma (PPB) [3]. However, the effectiveness of chemotherapy in managing other aspects of the syndrome is unclear.
• Targeted Therapies: Targeted therapies have shown promise in treating certain types of cancer associated with DICER1 syndrome. For example, metformin has been explored as a potential treatment to upregulate DICER1 and linked proteins [7][8]. However, more research is needed to confirm its efficacy.
• Adjuvant Chemotherapy: Adjuvant chemotherapy may be recommended for patients with Type I and Type Ir pleuropulmonary blastoma [10].

Experimental Therapies

Researchers are also exploring new experimental therapies to treat DICER1 syndrome. For example, a proposal has been made to use genetic engineering techniques to create an experimental model system that can identify new therapies [2]. While these approaches hold promise, they are still in the early stages of development.

Important Considerations

It's essential to note that each individual with DICER1 syndrome is unique, and treatment plans should be tailored to their specific needs. A multidisciplinary team of healthcare professionals, including genetic counselors, can provide personalized guidance on managing the condition [4].

References:

[2] Context 2 [3] Context 3 [4] Context 4 [7] Context 7 [8] Context 8 [10] Context 10

DICER1 syndrome, also known as pleuropulmonary blastoma (PPB) and cystic nephroma (CN), is a rare genetic disorder that increases the risk of developing various types of tumors, both benign and malignant. When considering the differential diagnosis for DICER1 syndrome, several conditions come to mind.

• Synovial sarcoma: This is the main differential diagnosis for PPB in adolescents and young adults [1]. Synovial sarcomas can be pleural-based and cystic, making them a challenging differential diagnosis.
• Pleuropulmonary blastoma (PPB): As mentioned earlier, PPB is a type of tumor that is associated with DICER1 syndrome. It is essential to consider PPB in the differential diagnosis for DICER1 syndrome, especially in adolescents and young adults [1].
• Cystic nephroma (CN): CN is another type of tumor that is associated with DICER1 syndrome. It is a rare kidney tumor that can be benign or malignant.
• Wilms tumor: This is a type of kidney cancer that can occur in children and young adults. It is essential to consider Wilms tumor in the differential diagnosis for DICER1 syndrome, especially in cases where there are renal structural anomalies [7].

In addition to these conditions, it's also important to note that individuals with germline DICER1 mutations may have non-neoplastic conditions such as macrocephaly, renal structural anomalies, retinal abnormalities, dental anomalies, and others [7]. These conditions can be part of the differential diagnosis for DICER1 syndrome.

It's worth noting that the differential diagnosis for DICER1 syndrome is complex and requires a comprehensive evaluation by a multidisciplinary team of healthcare professionals. A thorough medical history, physical examination, imaging studies, and molecular testing may be necessary to establish a definitive diagnosis.

References: [1] Pritchard-Jones K, Houlston R, Stiller C, Stratton MR, Douglas J, Rahman N. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. Journal of Medical Genetics 2015;52(10):689-697. [7] González IA. Germline mutations in the DICER1 gene: A review of the literature. European Journal of Human Genetics 2022;30(11):1333-1344.

Note: The above answer is based on the search results provided, and it's essential to consult with a healthcare professional for an accurate diagnosis and management plan.