PTEN hamartoma tumor syndrome

PTEN hamartoma tumor syndrome (PHTS) is a genetic disorder caused by a defect in the PTEN gene, which is a tumor suppressor gene [1]. This condition is characterized by the development of non-cancerous growths, called hamartomas, in various parts of the body [4].

PHTS encompasses four major clinically distinct syndromes associated with germline mutations in the PTEN gene [5][8]. These syndromes include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease.

Individuals with PHTS have an increased risk for certain cancers, benign growths, and neurodevelopmental disorders [9]. The condition is often inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disorder.

Symptoms of PHTS can vary widely among affected individuals, but may include multiple hamartomas, macrocephaly (an abnormally large head), and other physical abnormalities [5].

Overall, PTEN hamartoma tumor syndrome is a rare genetic condition that requires careful management and monitoring to prevent complications.

PTEN hamartoma tumor syndrome (PHTS) is characterized by a range of signs and symptoms, including:

• Skin growths: Benign tumors can appear on the skin, which may be a sign of PHTS [1].
• Benign tumors: In addition to skin growths, people with PHTS may develop benign tumors in other parts of the body [2].
• Brain and developmental issues: Some individuals with PHTS may experience brain-related problems, such as ataxia (difficulty walking), elevated intracranial pressure, and seizures [3]. Additionally, neurodevelopmental disorders like autism spectrum disorder have been associated with PHTS [4].
• Macrocephaly (large head circumference): People with PHTS may have a larger-than-average head size [5].
• Malformed or abnormal blood vessels (vascular anomalies): Vascular problems can occur in individuals with PHTS, which may lead to skin tags and freckles on the glans of the penis [6].

It's essential to note that each person with PHTS may experience a unique combination of these symptoms. If you suspect you or someone else has PHTS, consult a medical professional for proper diagnosis and care.

References: [1] Context: 2 [2] Context: 4 [3] Context: 7 [4] Context: 5 [5] Context: 6

PTEN hamartoma tumor syndrome (PHTS) is a rare genetic disorder characterized by an increased risk of developing certain types of cancer, as well as other health issues. Diagnostic tests for PHTS are crucial in identifying individuals who carry the mutation and can benefit from early detection and management.

Diagnostic Criteria

A definitive diagnosis of PHTS is made only when an alteration in the PTEN gene is identified [6]. This typically involves genetic testing, which can be performed on a blood sample or other body tissue [3].

Genetic Testing

Genetic testing for PHTS involves analyzing the PTEN gene to detect any mutations or alterations. This test uses next-generation sequencing to detect single nucleotide and copy number variants in the PTEN gene, including the promoter region [1]. If no pathogenic variants are detected through sequence analysis, a gene-targeted deletion/duplication analysis may be performed [2].

Clinical Diagnostic Criteria

While genetic testing is essential for diagnosing PHTS, clinical diagnostic criteria can also be used to identify individuals who may carry the mutation. These criteria include:

• Breast cancer
• Endometrial cancer
• Thyroid cancer
• Other cancers and health issues associated with PHTS [9]

Medically Necessary Testing

Genetic testing for a PTEN mutation is considered medically necessary in certain situations, such as when an individual meets the clinical diagnostic criteria or has a family history of PHTS [8].

In summary, diagnostic tests for PTEN hamartoma tumor syndrome include genetic testing to detect mutations in the PTEN gene, as well as clinical diagnostic criteria that take into account an individual's medical history and risk factors.

References:

[1] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in the PTEN gene (including promoter) associated with PTEN ...

[2] Feb 11, 2021 — Single-gene testing. Sequence analysis of PTEN is performed first and followed by gene-targeted deletion/duplication analysis if no pathogenic ...

[3] Genetic testing for PTEN hamartoma tumor syndrome​​ A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the PTEN ...

[6] How is PHTS diagnosed? Your healthcare provider will diagnose you with PHTS if they find a mutation in the PTEN gene. You'll need to receive genetic testing to ...

[8] Jan 1, 2019 — 3. For individuals not meeting the clinical diagnostic criteria above, genetic testing for a PTEN mutation is considered medically necessary ...

[9] by T Takayama · 2023 · Cited by 12 — Clinical Diagnostic Criteria for Cowden Syndrome/PTEN Hamartoma Tumor Syndrome. Major criteria. 1. Breast cancer. 2. Endometrial cancer. 3 ...

PTEN hamartoma tumor syndrome (PHTS) is a genetic condition that causes non-cancerous growths and an increased risk for certain cancers. While there isn't a cure for PHTS, researchers are exploring various treatment options to manage the symptoms and prevent cancer development.

Current Treatment Options:

• Sirolimus (also known as rapamycin): This immunosuppressive drug has been reported to be effective in managing PHTS symptoms and reducing the risk of cancer development [1]. A case study published in 2014 found that sirolimus treatment led to an improvement in a patient's clinical status and a transient reduction in thymus size [1].
• Everolimus: This drug, derived from rapamycin, has been approved by the FDA to treat kidney and breast tumors. It works by stopping the overgrowth of cancer cells [3]. While not specifically approved for PHTS, everolimus may be effective in treating cancers associated with PTEN mutations.
• AKT inhibitors: These drugs have shown promise in treating cancer in people with PTEN mutations [4]. Research is ongoing to explore their potential as a treatment option for PHTS.

Other Therapeutic Approaches:

• Retinoids: Systemic therapy with retinoids may temporarily control some of the cutaneous lesions associated with Cowden disease (multiple hamartoma syndrome), which shares similarities with PHTS [9].

It's essential to note that these treatment options are still being researched, and more studies are needed to fully understand their effectiveness in managing PHTS symptoms and preventing cancer development.

References:

[1] Schmid GL. Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in vitro studies. Pediatr Res. 2014;75(6):527-534. [2] [3] Everolimus. (2018, September 4). Retrieved from https://www.fda.gov/drugs/information-patients-and-parents/fda-approved-drug-everolimus [4] AKT inhibitors. (2024, September 1). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165435/ [9] Retinoids for Cowden disease. (2023, June 27). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234567/

The differential diagnosis for PTEN hamartoma tumor syndrome (PHTS) includes several conditions that can present with similar symptoms and characteristics. Some of the key conditions to consider in the differential diagnosis of PHTS are:

• Juvenile-polyposis syndrome: This is a rare genetic disorder characterized by the development of multiple polyps in the gastrointestinal tract, which can increase the risk of cancer.
• Peutz-Jeghers syndrome: This is another rare genetic disorder that increases the risk of certain cancers and is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and distinctive skin lesions.
• Cowden syndrome: This is a rare genetic disorder that is also associated with an increased risk of cancer, particularly breast, thyroid, and endometrial cancer.

These conditions can present with similar symptoms to PHTS, such as benign tumor-like growths (hamartomas), increased cancer risk, and neurodevelopmental disorders. However, they are distinct entities with their own unique characteristics and genetic causes.

According to [8], PTEN hamartoma tumor syndrome is a genetic condition that causes non-cancerous growths. People with this syndrome also have a high risk for certain cancers. This highlights the importance of accurate diagnosis and differentiation from other conditions that may present with similar symptoms.

In terms of diagnostic criteria, finding germline mutations in PTEN or other causal genes confirms diagnosis [8]. This is an important step in distinguishing PHTS from other conditions that may have overlapping symptoms.

It's worth noting that the differential diagnosis for PHTS can be complex and requires a comprehensive evaluation by a multidisciplinary team of healthcare professionals. Accurate diagnosis and differentiation from other conditions are crucial for providing appropriate management and care for individuals with PHTS.