Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome)

What causes Gorlin syndrome

Most cases are caused by a change in the PTCH1 gene, which normally acts as a brake on the hedgehog signaling pathway, a growth pathway active during development. When one copy of PTCH1 is faulty, the brake is weakened, and a second "hit" in a cell (often from UV light or radiation) can allow uncontrolled growth.

It is autosomal dominant: each child of an affected parent has a 50% chance of inheriting it. About a third or more of cases arise from a new gene change with no family history. Severity varies widely, even within families.

Signs and features

Skin

• Basal cell carcinomas (BCCs): often multiple, beginning in adolescence or early adulthood. Some people develop dozens or hundreds over a lifetime. They may look like skin-colored, pink or brown bumps resembling moles or skin tags, especially on the face, neck, chest and back
• palmar and plantar pits: small, shallow, pinpoint depressions on the palms and soles in most adults with the syndrome
• milia and small cysts on the skin

People with darker skin tend to develop fewer BCCs, likely because of natural UV protection.

Jaw

• odontogenic keratocysts: fluid-filled cysts in the jawbones, often first appearing in childhood or adolescence. They may cause swelling, pain, displaced teeth or no symptoms and are found on dental X-rays

Skeleton and head

• a larger head (macrocephaly) with a prominent forehead
• rib anomalies (bifid, fused or splayed ribs)
• spine differences such as scoliosis
• calcification of the falx cerebri (a membrane in the brain), seen on imaging in most adults with the syndrome

Other tumors

• medulloblastoma: a brain tumor in a small percentage of children, usually under age 3, more often with SUFU variants. It can block fluid flow and cause hydrocephalus
• ovarian and cardiac fibromas
• cleft lip or palate in some

Diagnosis

Diagnosis is based on clinical criteria (major and minor features) and confirmed by genetic testing. Major features include multiple BCCs or a BCC before age 20, jaw keratocysts, palmar or plantar pits, calcified falx cerebri, and an affected first-degree relative. Two major features, or one major and two minor, suggest the diagnosis.

Tests used:

• full skin examination
• panoramic dental X-ray (orthopantomogram)
• skull X-ray or MRI to detect falx calcification (avoiding unnecessary CT radiation)
• spine and chest imaging only when clinically needed
• genetic testing of PTCH1, SUFU and PTCH2

Treatment and surveillance

Skin cancers

BCCs grow slowly and rarely spread, but they can damage nearby tissue, especially on the face. Treatment options include:

• surgical excision or Mohs surgery for facial or high-risk lesions
• curettage and electrodesiccation
• topical treatments (imiquimod, 5-fluorouracil) for superficial BCCs
• photodynamic therapy
• hedgehog pathway inhibitors (vismodegib, sonidegib) as tablets for many or advanced BCCs; side effects such as muscle cramps, hair loss and taste changes are common

Radiation therapy should be avoided, because it triggers new BCCs in the treated area.

Jaw cysts

Keratocysts are removed surgically. They tend to recur, so dental X-rays are repeated regularly, often yearly from age 8.

Surveillance schedule

Expert guidelines suggest:

• skin exams from childhood, then every 3 to 12 months in adults, depending on the number of BCCs
• dental panoramic X-rays from about age 8, yearly until around 21 or until no cysts for 2 years
• regular head circumference checks and developmental assessment in infants
• MRI screening for medulloblastoma in young children with SUFU variants
• pelvic ultrasound and heart echocardiography at baseline

Prevention and daily life

• strict sun protection: sunscreen, hats, protective clothing, shade, no tanning beds
• minimize ionizing radiation: avoid unnecessary X-rays and CT scans; MRI and ultrasound are preferred
• regular self-checks of the skin
• genetic counseling for family planning

Life expectancy is generally normal. Other skin cancers, such as squamous cell carcinoma and melanoma, are not part of the syndrome but are checked for during routine skin cancer screening. The main burden is the frequent need to treat skin cancers and jaw cysts.

Frequently asked questions

What is Gorlin syndrome?

Gorlin syndrome is a rare inherited condition that causes many basal cell skin cancers, jaw cysts, pits on the palms and soles, and skeletal differences. It is usually caused by a change in the PTCH1 gene.

What are the first signs of Gorlin syndrome?

Early signs may include a large head, jaw cysts found on dental X-rays in childhood, pits on the palms or soles, and basal cell carcinomas appearing in the teens or twenties. Some children have a medulloblastoma in early childhood.

How is Gorlin syndrome treated?

There is no cure. Care focuses on regular skin and dental checks, early treatment of basal cell carcinomas by surgery, topical therapy or hedgehog inhibitor tablets, surgical removal of jaw cysts, sun protection and avoiding radiation.

Is Gorlin syndrome inherited?

Yes. It is autosomal dominant, so each child of an affected parent has a 50% chance of inheriting it. Many cases also arise from a new gene change with no family history.