SNP Shot: Genomic Insights

Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a disorder impacting multiple areas of the body, increasing the likelihood of both cancerous and non-cancerous growths.

Basal cell carcinoma, the most prevalent form of skin cancer, is the most commonly diagnosed cancer in individuals with Gorlin syndrome. These individuals typically start developing basal cell carcinomas in their teens or early twenties. These cancers frequently appear on the face, chest, and back. The number of basal cell carcinomas that arise over a person's lifetime differs among those affected. Some with Gorlin syndrome may never experience any, while others might develop thousands. People with lighter skin tones are more susceptible to developing basal cell carcinomas compared to those with darker skin. Continuous treatment can help reduce the number of carcinomas.

Most individuals with Gorlin syndrome also develop benign jaw tumors known as keratocystic odontogenic tumors. These tumors usually emerge during adolescence, with new tumors forming until approximately age 30. These tumors rarely develop later in adulthood. If left untreated, these tumors can lead to painful facial swelling and tooth displacement.

People with Gorlin syndrome face a higher risk than the general population of developing other tumors. A small percentage develop a childhood brain tumor called medulloblastoma. Benign tumors called fibromas can appear in the heart or in a woman's ovaries. Heart (cardiac) fibromas often present no symptoms, but they may obstruct blood flow or induce irregular heartbeats (arrhythmia). Ovarian fibromas are not believed to affect a woman's ability to conceive (fertility).

Additional characteristics of Gorlin syndrome include small indentations (pits) on the skin of the palms and soles; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal irregularities affecting the spine, ribs, or skull. These signs and symptoms are generally noticeable from birth or become apparent in early childhood.

Inheritance:

Gorlin syndrome follows an autosomal dominant inheritance pattern, meaning that possessing one altered copy of the responsible gene in each cell is sufficient to cause the condition. In the majority of cases, an affected individual inherits the altered gene from one affected parent. Other cases arise from new mutations in the gene and occur in individuals with no family history of the disorder. Having one mutated copy of the PTCH1 gene in each cell is enough to cause the features of Gorlin syndrome that are present early in life, including macrocephaly and skeletal abnormalities. The development of basal cell carcinomas and other tumors requires a second mutation in the other copy of the PTCH1 gene in specific cells during the person's lifetime. Most people born with one PTCH1 gene mutation eventually acquire a second mutation in some cells, leading to the development of various types of tumors.