Everything You Need to Know About PTCH1

Patched-1, or PTCH1, is a tumor suppressor gene, meaning it helps prevent certain types of cancers from developing. When you have a PTCH1 mutation, the gene’s cancer-suppressing effect no longer works.

“There are over 100 clinical abnormalities that can happen,” says Joe Mignone, MD, oncologist and cofounder of SurvivorRx. They’re “usually diagnosed at a young age, but they may not be detected in some until their teens or young adulthood.”

“A PTCH1 mutation is rare, estimated to be between 1 in 31,000 to 1 in 164,000,” says Dr. Mignone. “True numbers may be higher, as some people with mild features and symptoms may never be diagnosed.”

Most people with a PTCH1 mutation will inherit the PTCH1 gene variant from their parents, but it is still possible to spontaneously develop the mutation later in life. Mignone says that 70 to 80 percent of the risk factors and causes are inherited, with 20 to 30 percent occurring spontaneously, or de novo.

Gorlin syndrome is rare, affecting 40,000 to 60,000 individuals. It affects men and women equally and is present in all races, though African American and Asian individuals may have a lower risk of the condition, making up 5 percent of all cases.

Gorlin syndrome can lead to the development of both noncancerous and cancerous tumors and developmental abnormalities, including:

• Keratocystic odontogenic tumors, or noncancerous (benign) tumors of the jaw
• Medulloblastoma, a type of cancerous, fast-growing brain tumor that develops in the cerebellum

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• Cardiac or ovarian fibromas, which are typically benign tumors

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• Superficial pits in the palms and soles of the feet, which around 75 to 90 percent of people with Gorlin syndrome have

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• Macrocephaly, or a very large head

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In addition, “Those with PTCH1 mutations can have bone and eye problems,” says Mignone. “The mutation is also associated with cleft lip or palate, and those with the mutation may be born with extra fingers or toes.”

While experts know that PTCH1 mutations can cause an increased risk of certain cancers, they are not as certain how the mutation relates to other changes associated with Gorlin syndrome.

“PTCH1 genetic testing typically uses saliva or blood, and someone should be tested whenever they have any features or family history of Gorlin syndrome,” says Mignone.

Kenneth Mark, MD, a cosmetic dermatology expert in New York City, also recommends that people with a family history of a PTCH1 mutation undergo testing for it.

If you’re looking to start a family, you may want to undergo prenatal testing if you or your partner has a PTCH1 mutation. “If a parent has the gene, then there is a 50 percent chance of the fetus acquiring it as well,” says Mignone. It is always advised to meet with a genetic counselor so that proper testing is performed.”

Having a risk factor for cancer does not mean you will develop cancer. It just means you have a higher risk compared with someone who doesn’t have the mutation.

If testing confirms you have a PTCH1 mutation:

• Contact your doctor to discuss your results and their recommended next steps.
• Schedule a meeting with a genetic counselor if you’re planning on getting pregnant.
• Discuss screening schedules for skin cancers, as well as any other cancers you have a family history of, with your doctor.
• Take extra precautions to protect your skin, such as wearing sunscreen, staying in shade, and wearing large hats when you’re outside.

• X-rays
• Magnetic resonance imaging of the brain to check for tumors
• Total body skin exams
• Echocardiogram to check for heart fibromas
• Ultrasounds of the heart and ovaries
• Yearly hearing, vision, and speech evaluations

Researchers are continually looking into potential new therapies that target the hedgehog signaling pathways. Several clinical trials are either ongoing or recently finished. As novel treatments successfully go through clinical trials, new therapies may become available to treat cancers caused by PTCH1 mutations.

• The PTCH1 gene helps prevent cancers from forming, but some people have mutations that make the gene less effective.
• PTCH1 mutations are strongly associated with Gorlin syndrome, a hereditary condition that can increase your risk of basal cell skin cancers and developmental abnormalities, as well as other types of cancer, such as nonhereditary skin cancers, breast cancer, and colon cancer.
• If you test positive for a PTCH1 mutation, it doesn’t mean you will develop cancer. Your doctor will likely recommend getting early and frequent cancer screenings in order to detect any growths or changes early on.