Definition

Basal cell nevus syndrome is a group of conditions affecting the skin, nervous system, eyes, endocrine glands, urinary tract, reproductive systems, and bones. Basal cell nevus syndrome is characterized by a mutation in a specific gene responsible for suppressing the development of tumors and regulating the growth of cells. This condition will result in an unusual facial appearance and individuals affected by it will have an increased susceptibility to developing skin cancer (such as basal cell carcinoma) as well as other benign growths (non-cancerous tumors).

Basal cell nevus syndrome is a medical condition often referred to as Gorlin syndrome, Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome, and basal cell carcinoma nevus syndrome.

Basal cell nevus syndrome is an uncommon hereditary condition that often runs in the family. The prevalence of basal cell nevus syndrome is estimated to be 1 case per 40,000 individuals. Basal cell nevus syndrome can be broadly classified into two types:

• Hereditary: Approximately 70% of individuals with this condition inherit it from their family.
• Spontaneous: Approximately 30% of individuals with basal cell nevus syndrome get it spontaneously and not inherited, indicating that they possess a random genetic mutation.

Causes

Basal cell nevus syndrome is an uncommon hereditary condition. The etiology of this condition is attributed to mutations in the PTCH genes, specifically PTCH1 and PTCH2. PTCH1 ("patched gene") mutations account for 50-85% of all instances of basal cell nevus syndrome. In addition, this condition has also been associated with another gene known as SUFU. These genes are responsible for regulating the normal proliferation of cells in the body. 

When a mutation occurs in this gene, it impairs the body's ability to regulate cell division and growth. Consequently, the body is unable to inhibit the proliferation of specific forms of cancer. The gene mutations are primarily inherited within families as an autosomal dominant pattern. If one of your parents has transmitted the gene to you, you could experience this syndrome in the future. Nevertheless, basal cell nevus syndrome can occur even in the absence of a familial background.

Risk factor

Basal cell nevus syndrome can impact individuals of all genders equally, without any predilection for a certain gender. While the disease has the potential to impact individuals from all races, people of African or Asian descent have a lower probability of being affected by this. The most important risk factor in the development of basal cell nevus syndrome is a familial predisposition to this condition. If one of your parents is affected by basal cell nevus syndrome, there is a 50% probability that you could also have this condition in the future.

Symptoms

The symptoms and signs associated with basal cell nevus syndrome may vary. The prevailing symptoms and signs encompass:

• Basal cell carcinoma, the predominant kind of skin cancer, frequently manifests on the face, hands, or neck
• A keratocystic odontogenic tumor could appear, it is a benign cyst that often develops in the jawbone during adolescence and persists until about the age of 30
• A palmoplantar pit refers to a tiny indentation found on the soles of the feet or palms of the hands

In addition to these, many other, less prevalent symptoms could be observed, including:

• Brain tumors, such as meningioma or medulloblastoma (malignant brain tumors, typically found in children).
• Cleft lip or cleft palate.
• Various eye conditions, such as strabismus (crossed eyes), microphthalmia (small eyes), cataracts, or nystagmus (rapid eye movements).
• Ovarian fibroma refers to the development of tumors in the ovaries.
• A cardiac fibroma, a neoplasm located in the heart, characterized by an abnormal proliferation of cells that can lead to arrhythmias.
• Frontal bossing refers to a large forehead, while hypertelorism is characterized by an increased distance between the eyes.
• Bone abnormalities affecting the ribs, spine, or cranium, such as scoliosis or kyphosis.
• Excessive head circumference (macrocephaly).
• Facial milia, white lumps or cysts that appear on the skin.
• Wide nose.
• Thick and prominent eyebrows.
• Protruding jaw (in certain instances).
• Hearing impairment.
• Intellectual disability.
• Seizures. 

Diagnosis

When diagnosing basal cell nevus syndrome, the doctor begins the process by having a medical interview with you. The doctor will inquire about the symptoms you are currently having, the duration of these symptoms, and any relevant familial history of such conditions. After that, the doctor will do a physical examination to identify signs of basal cell nevus syndrome. In addition, they may do diagnostic tests to help confirm this diagnosis, including:

• Tests are conducted to identify particular gene mutations in samples of blood, hair, or skin
• MRI of the brain
• Cranial CT scan
• Ultrasound examination of the abdomen
• Radiographic imaging of bone, teeth, and skull
• Cardiac echocardiography

The diagnosis of basal cell nevus syndrome can be established if one of the following two criteria is fulfilled:

• Exhibits two major indicators and one minor indicator
• Exhibits one major indicator and three minor indicators

The major indicators encompass:

• Familial history of basal cell nevus syndrome
• Experiencing the occurrence of two or more basal cell carcinomas before the age of 30
• Keratocystic odontogenic tumor
• Palmoplantar pit
• Calcium deposits in the brain.

Some of the minor indicators include:

• Medulloblastoma, a type of malignant brain tumor in children
• Macrocephaly, characterized by an abnormally large head, along with a broad forehead
• Possessing extra digits on the hands or feet
• Cleft lip
• Cleft palate
• Abnormally shaped spine or ribs
• Small eyes
• Iris neoplasm
• Cataract 
• Ovarian fibroma
• Cardiac fibroma 
• Abdominal cyst
• Calcified ovarian cyst 

Management

A cure for basal cell nevus syndrome has yet to be identified. The focus of your lifelong treatment will revolve around the prevention, monitoring, and management of symptoms. This will entail conducting basic testing and analysis of body regions that are prone to the development of tumors and fibromas, including the brain, jaw, heart, and ovaries.

Treatment options for basal cell nevus syndrome focus on the management of symptoms, such as:

Skin cancer treatment

If you are diagnosed with basal cell carcinoma, treatment for skin cancer may involve:

• Applying topical chemotherapy to the skin.
• Cryotherapy is a medical procedure used to treat skin cancer by freezing the affected area.
• Medications and advanced laser technology to eradicate skin cancer (photodynamic therapy).

Surgical procedure

If you have a jaw tumor or cyst, your doctor can perform surgery to remove it. Mohs surgery is a technique used by doctors to excise damaged skin tissue in cases of basal cell carcinoma.

Complications

Basal cell nevus syndrome most frequently leads to the development of basal cell carcinoma, a prevalent form of skin cancer. Another potential complication that may arise is the loss of vision or hearing as a result of injury to the nerves responsible for these senses.

Prevention

Currently, there is no known established method to avoid basal cell nevus syndrome. Individuals who are in a relationship and have a familial background of basal cell nevus syndrome may need to consider seeking genetic counseling before conceiving a child. To prevent the development of basal cell carcinoma in individuals with basal cell nevus syndrome, it is advisable to avoid direct sunlight and use sunscreen. In addition, individuals with basal cell nevus syndrome are strongly recommended to stay away from radiation, such as X-rays, due to their increased sensitivity to radiation, which might potentially induce the development of skin cancer.

When to see a doctor?

If you encounter signs of basal cell nevus syndrome, particularly if there is a familial predisposition to the condition, it is advisable to get medical advice from a doctor.

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