Which are the causes of Cowden syndrome?

Cowden syndrome, also known as Cowden's disease or multiple hamartoma syndrome, is a rare genetic disorder that is characterized by the development of multiple noncancerous growths called hamartomas. These growths can affect various parts of the body, including the skin, mucous membranes, gastrointestinal tract, thyroid, breast, and central nervous system. Cowden syndrome is caused by mutations in the PTEN gene, which is a tumor suppressor gene.

The PTEN gene:

The PTEN gene provides instructions for producing a protein called phosphatase and tensin homolog. This protein helps regulate cell growth and division by controlling the signaling pathways that prevent cells from growing and dividing too rapidly or in an uncontrolled manner. It also plays a crucial role in maintaining the stability of the cell's genetic material.

Mutations in the PTEN gene:

In individuals with Cowden syndrome, mutations in the PTEN gene impair the function of the protein it produces. These mutations can be inherited from a parent or occur spontaneously during a person's lifetime. Inherited mutations follow an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the syndrome.

Signs and symptoms:

The signs and symptoms of Cowden syndrome can vary widely among affected individuals. Some of the most common features include:

• Multiple skin abnormalities: These may include trichilemmomas (benign tumors of the hair follicles), acral keratoses (thickened, wart-like growths on the hands and feet), and papillomatous papules (small, raised bumps on the skin).


• Macrocephaly: An abnormally large head size.


• Thyroid abnormalities: Such as goiter (enlarged thyroid gland) or thyroid nodules.


• Breast abnormalities: Women with Cowden syndrome have an increased risk of developing benign breast tumors (fibroadenomas) and a significantly higher risk of developing breast cancer.


• Gastrointestinal polyps: These are noncancerous growths that can occur in the stomach, small intestine, or colon.


• Benign uterine growths: Women may develop uterine fibroids, which are noncancerous tumors in the uterus.


• Intellectual disability: Some individuals with Cowden syndrome may have learning difficulties or intellectual disabilities.

Risk factors:

Having a family history of Cowden syndrome or a known PTEN gene mutation increases the risk of developing the condition. However, it is important to note that not all individuals with a PTEN gene mutation will develop Cowden syndrome, and the severity of symptoms can vary even among affected family members.

Diagnosis:

Diagnosing Cowden syndrome can be challenging due to its variable presentation and overlap with other conditions. A thorough medical evaluation, including a detailed family history, physical examination, and various tests, is necessary for an accurate diagnosis. Genetic testing can identify mutations in the PTEN gene and confirm the diagnosis.

Management and treatment:

There is currently no cure for Cowden syndrome, so treatment focuses on managing the individual symptoms and reducing the risk of associated complications. Regular screenings and surveillance are essential to detect and manage potential complications early. This may involve regular skin examinations, breast imaging, thyroid function tests, colonoscopies, and other screenings based on individual risk factors.

Conclusion:

Cowden syndrome is a rare genetic disorder caused by mutations in the PTEN gene. It is characterized by the development of multiple hamartomas in various parts of the body. Early diagnosis and appropriate management are crucial in reducing the risk of associated complications, including an increased risk of certain cancers. Genetic counseling and testing are recommended for individuals with a family history of Cowden syndrome or those exhibiting symptoms associated with the condition.