PTEN Hamartoma Syndrome (PHS) is a rare genetic condition characterized by non-cancerous growths called hamartomas, which can appear in various body systems. It encompasses a group of related disorders, including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and some forms of Proteus syndrome. While hamartomas are typically benign, individuals with PHS also face an increased risk of developing certain cancers. Recent studies suggest its prevalence may be higher than previously thought, potentially affecting approximately 1 in 9,000 to 1 in 13,000 individuals in the general population.
Underlying Genetics
PTEN Hamartoma Syndrome arises from alterations in the PTEN gene, located on chromosome 10. This gene is a tumor suppressor, meaning it normally produces an enzyme that helps regulate cell growth and division, signaling cells to stop dividing and promoting programmed cell death. When the PTEN gene is mutated, this regulatory function is impaired, leading to uncontrolled cell proliferation and the formation of hamartomas.
The inheritance pattern for PHS is autosomal dominant, meaning only one altered copy of the PTEN gene is sufficient to cause the syndrome. An affected individual has a 50% chance of passing the altered gene to each of their children. While PHS is often inherited, a significant portion of cases can also arise from new, spontaneous mutations in the PTEN gene.
Diverse Clinical Features
PHS presents with a wide array of signs and symptoms affecting multiple organ systems, with varying severity among individuals. Skin and mucous membrane manifestations are common, often appearing before age 20. These include trichilemmomas (benign hair follicle tumors, especially on the face), papillomatous papules (small, flesh-colored nodules on the skin or mouth), lipomas (fatty nodules under the skin), and acral keratoses (thickened skin on hands and feet). Some individuals may also develop vascular malformations.
Gastrointestinal involvement frequently includes hamartomatous polyps throughout the digestive tract. While many polyps are benign, there is an increased risk for adenomatous polyps, which can progress to cancer. Neurological features are also prominent, with macrocephaly (a larger-than-average head size) observed in a high percentage of patients, often due to overgrowth of brain tissue. Developmental delays, intellectual disabilities, and autism spectrum disorder are also reported in individuals with PHS.
The lifetime risk for breast cancer in women with PHS can be as high as 85%, with diagnoses often occurring at a younger age. Thyroid issues are common, including goiter and adenomas, with an increased risk of thyroid cancer, including follicular thyroid cancer. Other elevated cancer risks include endometrial cancer (up to 28% lifetime risk for women), kidney cancer (up to 34% lifetime risk), and colorectal cancer.
Diagnosis and Identification
The diagnosis of PTEN Hamartoma Syndrome typically begins with clinical suspicion based on a person’s physical findings and family history. Healthcare providers often use specific clinical diagnostic criteria, such as those developed by the Cleveland Clinic, to guide the initial assessment. These criteria consider a combination of major and minor features characteristic of PHS.
A definitive diagnosis of PHS relies on genetic testing to identify a pathogenic mutation in the PTEN gene. This is usually performed through DNA sequencing from a blood sample, confirming the gene alteration and distinguishing PHS from other conditions.
Ongoing Care and Monitoring
Managing PTEN Hamartoma Syndrome involves a proactive, multidisciplinary approach due to its varied manifestations and cancer risks. A team of specialists, including dermatologists, neurologists, gastroenterologists, and oncologists, collaborates to provide comprehensive care, ensuring all affected body systems are regularly monitored.
Rigorous cancer surveillance is a significant aspect of ongoing care, tailored to the specific risks associated with PHS. For women, this includes regular breast cancer screenings, often starting with annual mammograms and breast MRIs at an earlier age (typically 25-30 years or younger if there’s a strong family history). Colonoscopies are recommended to screen for polyps and colorectal cancer, usually beginning in early adulthood. Thyroid ultrasounds are performed regularly to monitor for nodules and thyroid cancer. Kidney and endometrial surveillance are also important, often involving regular renal ultrasounds and, for women, endometrial biopsies.
Beyond cancer screening, management also addresses non-cancerous manifestations, such as neurological issues or skin lesions, with appropriate medical or surgical interventions. Genetic counseling is strongly recommended for affected individuals and their families to understand inheritance patterns and family planning implications.