SNP Shot: Genomic Insights

Cowden syndrome is a genetic condition distinguished by the presence of multiple non-cancerous growths called hamartomas, and a heightened risk of developing specific cancers.

Hamartomas are a near-universal characteristic of Cowden syndrome. These growths commonly appear on the skin and mucous membranes (such as the linings of the mouth and nose), but can also occur in the intestines and other areas of the body. Skin and mucous membrane hamartomas usually become noticeable before the age of 30.

Cowden syndrome is linked to an increased likelihood of developing cancers of the breast, thyroid gland, and the uterine lining (endometrium). Kidney cancer, colorectal cancer, and melanoma, a serious type of skin cancer, have also been observed in individuals with Cowden syndrome. Compared to the general population, those with Cowden syndrome tend to develop these cancers at a younger age, often in their thirties or forties. They are also more susceptible to developing multiple cancers throughout their lives. Other conditions affecting the breast, thyroid, and endometrium are also common. Additional symptoms can include an abnormally large head size (macrocephaly) and a rare, non-cancerous brain tumor known as Lhermitte-Duclos disease. A small percentage of individuals may experience developmental delays, intellectual disability, or autism spectrum disorder, potentially impacting communication and social skills.

Some individuals exhibit features suggestive of Cowden syndrome, particularly the development of related cancers, but do not fully meet the diagnostic criteria. These individuals are often diagnosed with Cowden-like syndrome. Both Cowden syndrome and Cowden-like syndrome are caused by mutations in the same genes.

Cowden syndrome shares characteristics with another condition called Bannayan-Riley-Ruvalcaba syndrome. Individuals with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other non-cancerous tumors. Some Cowden syndrome patients have relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, while others display features of both conditions. Due to these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of related conditions, known as PTEN hamartoma tumor syndrome (named after the gene responsible), rather than two separate disorders.

Inheritance:

Cowden syndrome and Cowden-like syndrome follow an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is needed to cause the condition and increase cancer risk. In some cases, the altered gene is inherited from an affected parent. However, in other cases, the mutation occurs spontaneously. These new mutations occur in individuals with no family history of the disorder.