Gorlin syndrome: Year of the Zebra

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Gorlin syndrome is a rare genetic disorder that affects approximately 1 in 31,000 people worldwide. At the most basic level, people with Gorlin syndrome have an increased lifetime risk of tumors, both cancerous and non-cancerous, in nearly any organ of their body.
The most common tumor experienced is a skin cancer called basal cell carcinoma, so the disease is also known as basal cell carcinoma nevus syndrome.
Because of the rarity of the disease, your doctors might not recognize or know much about Gorlin syndrome. Medical care may be delayed or compromised if it is not identified, so it is important for people with Gorlin syndrome and their family members to learn about the syndrome and be able to effectively manage care.
Gorlin syndrome is caused by a defect in a gene that suppresses tumors in a person’s body. Genes are like instructions for cells.
Every cell has two copies of each gene. We inherit one gene from each parent.
Sometimes, we inherit a mutated gene from one parent, and sometimes a gene mutates on its own. If one gene is mutated then the other gene can suppress tumor growth on its own to a degree.
This means that if a person with Gorlin syndrome has only one broken copy of a tumor suppressing gene in each cell, they may have some features of the disease.
If any cell in their body develops a second mutation that affects the working copy of the tumor suppressing gene, then the cell has no way to prevent itself from replicating out of control.The cells will begin to pile up into a mass, and a tumor will form.
People with Gorlin syndrome usually have tumor growth at some point in their lives, but how many develop, at what age and which organs are affected is variable.
There are three genes known to cause Gorlin syndrome: PTCH1, PTCH2 and SUFU. Genetic testing may identify which defect you have.
The specific gene that is altered can affect which manifestations and symptoms you experience. A genetic counsellor can explain the risks associated with your specific gene mutation.
Gorlin syndrome commonly causes changes in the skin. A person with Gorlin syndrome will need a dermatologist to identify, monitor and potentially treat any skin changes.
One signature of the disease are tiny pits that may appear as small holes on the palms of the hands and soles of the feet but do not usually require treatment.
Basal cell carcinomas may develop during childhood and the risk increases with age. They are slow growing and rarely spread, if treated early and regularly, therefore lifelong monitoring by a dermatologist is important..
BCCs can appear as flesh-colored, tan to brown spots, or red patches. The sheen can be pearly, waxy, or shiny.
The texture may appear flat, scaley or like elevated bumps. They are typically located on areas of the skin that are exposed to ionizing radiation, commonly from UV sunlight or X rays, but can occur on all areas of the skin.
In the jaw bones, benign but destructive Odontogenic Keratocysts may form. These cysts are common during childhood and adolescence and may continue to appear throughout adulthood.
Odontogenic Keratocysts typically begin as painless, but if they grow big enough, they can cause pain, displace teeth and erode bone.
Because of the risk of tooth or bone loss, it is important for everyone to be monitored by an oral surgeon throughout their life so the cysts can be removed before they cause irreversible damage.The syndrome may cause abnormal bone development throughout the skeletal system.
This most often appears as being taller or having a larger head size than average. It can also appear as misshapen ribs, an overly curved spine, or extra fingers or toes.
Some facial changes may occur such as cleft lip and palate or a prominent forehead. The brain can be impacted by the syndrome in several ways, though only some of them will cause symptoms.
Gorlin syndrome can cause hydrocephalus or medulloblastomas, usually in infancy or early childhood. Hydrocephalus is an excess of fluid in the brain, which can raise pressure in the skull and may lead to an increase in head circumference in infancy or brain injury at any age.
Medulloblastoma is a brain cancer that occurs at the base of the brain. Individuals with the SUFU gene mutation have a higher risk of developing medulloblastoma.
Both medulloblastoma and hydrocephalus are most common during infancy and early childhood. They can be asymptomatic, or cause headaches, nausea, vomiting, balance loss, and seizure, so careful monitoring is always necessary.
Care by a neurosurgeon should be sought promptly if these problems arise. Finally, fibroid tumors can develop in organs including the heart and ovaries.
Your physicians should be made aware that you are at increased risk of fibromas. In the heart fibromas can cause fatigue, shortness of breath, and irregular heartbeat.
Calcified ovarian fibromas can develop in the ovaries, causing pain or abnormal menstruation. If caught and treated early, they usually don’t impact fertility.
People with Gorlin syndrome who have ovaries should start seeing a gynecologist when they begin their period or when symptoms present.
Gorlin syndrome can manifest in many different ways, so it is important to work closely with your care team and stay educated about the disease.
Children should attend routine well-child visits, and follow up with specialists as recommended. Education, genetic counseling, and working with specialists in the body systems affected can provide individuals of any age with an idea of what to expect and how best to navigate their individual manifestations.
To reduce the risk of basal cell carcinomas, precautionary measures should be taken including avoiding ionizing radiation, and UV sunlight, wearing UV protective clothing, hats, and sunglasses; and wearing sunblock or sunscreen when outside.
It may feel overwhelming to keep track of all symptoms and manage care but you are not alone. The Gorlin Syndrome Alliance supports anyone impacted by the syndrome and can provide you with resources and personal connections.
There is a surge in interest in the discovery of new treatments and diagnostic tools for the manifestations of the syndrome.
You can help the Gorlin Syndrome Alliance and its collaborators gain a better understanding of the characteristics of Gorlin syndrome by entering de-identified information into the Gorlin Syndrome Alliance Patient Registry and help pave the way for an improved quality of life.
We are here to help you expertly manage the manifestations. Skillful, knowledgeable management of Gorlin syndrome is possible, and will give you the freedom to enjoy a rich,
Gorlin syndrome: Video, Causes, and Symptoms | Osmosis