Gorlin Syndrome is a rare genetic condition that impacts various body systems. It leads to a predisposition for developing certain tumors, both cancerous and noncancerous, and can cause a range of physical characteristics.
What is Gorlin Syndrome?
Gorlin Syndrome, also known as Nevoid Basal Cell Carcinoma Syndrome (NBCCS), is a hereditary disorder. This condition arises from a mutation in a tumor suppressor gene, most commonly the PTCH1 gene, located on chromosome 9. Mutations in other genes like SUFU or PTCH2 can also cause similar features. The PTCH1 gene provides instructions for producing a protein called patched-1, which normally helps control cell growth and division. When this gene is mutated, the patched-1 protein cannot effectively suppress cell proliferation, leading to the formation of tumors characteristic of the syndrome.
The inheritance pattern of Gorlin Syndrome is autosomal dominant. This means an individual only needs to inherit one copy of the mutated gene from a parent to develop the condition. In most cases, an affected person inherits the mutation from one affected parent. However, some instances result from new mutations, where the individual develops the condition without a family history. The way the syndrome manifests can vary greatly among individuals, even within the same family, due to differing penetrance and expressivity of the gene mutation.
Recognizing the Key Features
A common manifestation involves the skin, specifically the development of basal cell carcinomas (BCCs). These skin cancers typically begin to appear during adolescence or early adulthood, and their number can vary significantly among affected individuals. Small pits on the palms and soles are another characteristic dermatological sign.
Skeletal abnormalities are frequently observed. These include jaw cysts (odontogenic keratocysts), which often emerge during adolescence. Rib anomalies, such as bifid or splayed ribs, and vertebral defects like fused vertebrae or scoliosis, are also common. Macrocephaly (unusually large head size) with a prominent forehead can also be present.
Neurological features include medulloblastoma, a brain tumor that affects a small proportion of children. This type of tumor is more commonly associated with SUFU gene mutations. Hydrocephalus (fluid buildup in the brain) is another neurological concern. Other features include eye abnormalities (e.g., strabismus, cataracts) and benign tumors like ovarian fibromas in females.
Diagnosis and Ongoing Management
The diagnosis of Gorlin Syndrome typically involves a combination of clinical examination, imaging studies, and genetic testing. Healthcare providers look for specific clinical criteria, such as the presence of multiple basal cell carcinomas or jaw cysts, along with other characteristic features. Imaging techniques like X-rays identify skeletal anomalies, including jaw cysts, rib abnormalities, and calcification of the falx cerebri in the brain. Magnetic resonance imaging (MRI) may screen for brain tumors like medulloblastoma, especially in children.
Genetic testing confirms diagnosis by identifying mutations in the PTCH1, SUFU, or PTCH2 genes. This testing can also be used for predictive purposes in family members. A confirmed genetic mutation helps solidify the diagnosis, particularly when clinical signs are mild or atypical.
Ongoing management of Gorlin Syndrome requires a multidisciplinary approach. Dermatologists routinely monitor for and treat basal cell carcinomas, often through surgical removal. Oral surgeons manage jaw cysts, which may require repeated procedures. Regular screenings detect potential complications early, such as annual skin examinations and periodic imaging for tumors. Lifelong follow-up care addresses new manifestations and provides appropriate interventions.