Cowden disease is a rare inherited disorder identified by the development of multiple noncancerous growths, referred to as hamartomas. These growths can appear in various parts of the body, including the skin, mucous membranes, and internal organs. Individuals with Cowden disease also face an increased likelihood of developing certain types of cancer during their lifetime.
Genetic Origins of Cowden Disease
Cowden disease is caused by a mutation in a gene known as PTEN. The PTEN gene functions as a tumor suppressor, regulating cell growth and division. When a PTEN mutation occurs, its function is impaired, leading to the formation of hamartomas and an elevated risk for cancerous tumors.
This condition follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated PTEN gene from either parent is needed to develop the disorder. The mutation can be inherited from an affected parent or arise spontaneously in individuals with no family history. The PTEN gene is located on chromosome 10q23.3.
Recognizing the Signs
Observable signs and internal manifestations of Cowden disease often begin to appear by the late twenties. Nearly all affected individuals develop characteristic skin and mucous membrane lesions. These include trichilemmomas, which are wart-like growths frequently observed on the face.
Papillomatous papules can also be present on the skin and mucous membranes, alongside oral lesions that may have a cobblestone appearance. Macrocephaly, an abnormally large head size, is another common feature. Beyond external signs, hamartomas can develop internally in various organs.
These internal growths commonly affect the thyroid gland, manifesting as goiters or adenomas. Fibrocystic disease and fibroadenomas of the breasts are frequently observed in females. The intestinal tract can also develop hamartomatous polyps.
The Diagnostic Process
Confirming a diagnosis of Cowden disease combines clinical assessment with genetic analysis. Doctors first evaluate a patient against established major and minor diagnostic criteria. These criteria consider the presence of specific clinical features, such as characteristic mucocutaneous lesions, macrocephaly, or a history of certain cancers. For example, an operational diagnosis might be made if a patient displays specific mucocutaneous lesions, or a combination of major and minor criteria, such as two major criteria with one being macrocephaly.
The clinical assessment also includes a thorough review of the patient’s medical and family history. A definitive diagnosis is then established through genetic testing, which aims to identify a mutation in the PTEN gene. Finding a germline mutation in PTEN provides confirmation of the diagnosis and is often considered medically necessary when specific clinical signs are present. This genetic confirmation guides subsequent surveillance and management strategies.
Associated Cancer Risks and Surveillance
Individuals with Cowden disease face an increased lifetime risk of developing several specific cancers, often at a younger age than in the general population. The primary cancers associated with this condition include breast cancer, affecting both females and males, with women having an estimated lifetime risk ranging from 25% to 50%. Thyroid cancer, particularly the follicular type, is another heightened risk, with estimates ranging from 3% to 38%.
Endometrial (uterine) cancer is a concern for females, with risks typically between 13% and 30%. Colorectal cancer and kidney cancer also show an elevated incidence in affected individuals, with risks for colorectal cancer ranging from 5% to 10% and kidney cancer from 2% to 5%. Given these increased risks, proactive monitoring and screening protocols are recommended to detect any malignancies early.
Surveillance typically begins with annual thyroid ultrasound exams starting around age seven. For women, yearly mammograms and breast MRIs are often recommended beginning at age 30, or 10 years before the earliest known breast cancer in the family. Colonoscopies are generally advised every five years, starting around age 35, or earlier if symptoms are present or if there is a family history of early-onset colorectal cancer. Consideration for endometrial cancer screening, possibly with transvaginal ultrasounds or endometrial biopsies, may begin around age 35 for females. Additionally, yearly full physical examinations and skin exams are recommended.