Basal Cell Nevus Syndrome: All You Need to Know

What Are the Other Names for Basal Cell Nevus Syndrome?

Following are the different names of this syndrome:

• Collapse Section.

• Basal cell nevus syndrome.

• BCNS.

• Gorlin Syndrome.

• Gorlin-Goltz syndrome.

• NBCCS.

• Nevoid basal cell carcinoma syndrome.

What Is the Frequency of Basal Cell Nevus Syndrome?

Basal cell nevus syndrome affects an estimated one in 31,000 people. While more than one million new cases of basal cell carcinoma are diagnosed each year in the United States, fewer than one percent of these skin cancers are related to this syndrome. In addition, the disease affects men and women in relatively equal distribution (1:1.3). Although the disease affects all races, Africans, Americans, and Asians represent only five percent of cases.

What Is the Pathophysiology of Basal Cell Nevus Syndrome?

• Any mutation in patched 1 (PTCH1), a tumor suppressor gene located on chromosome 9q, causes basal cell nevus syndrome. The PTCH gene encodes a transmembrane receptor protein that recognizes signaling proteins due to homozygous inactivation of the PTCH gene and the formation of multiple basal cell carcinomas and other associated neoplasms.

• Patients with basal cell nevus syndrome inherit one defective copy of the tumor suppressor gene, which leads to a "second hits" mutation, such as from ultraviolet light or ionizing radiation. Recently, mutations in the suppressor of a fused gene (SUFU) on chromosome 10q and PTCH2 on chromosome 1p have been found in patients suffering from Gorlin's syndrome. Patients with SUFU mutations have a 20-fold higher risk of developing medulloblastoma than those with PTCH1 mutations in Gorlin syndrome.

• If there is one mutated copy of the PTCH1 gene in each cell, the characteristics of Gorlin syndrome, such as skeletal abnormalities and microcephaly, are evident. However, a mutation in the second copy of the PTCH1gene must also occur in specific cells during the person's lifetime for basal cell carcinomas and other tumors to develop. Therefore, patients with one PTCH1 gene mutation eventually develop a second mutation in some cells and consequently develop various tumors.

What Are the Risk Factors for Basal Cell Nevus Syndrome?

The following are the factors that increase basal cell nevus syndrome:

1. Chronic Sun Exposure: Severe sunburns also increase the risk of basal cell carcinoma.

2. Radiation Therapy: Radiation therapy used to treat acne or other skin-related conditions may increase the risk.

3. Fair Skin: People with freckles, fair skin, red or blonde hair, or light-colored eyes are at significant risk.

4. Immune-Suppressing Drugs: Drugs like anti-rejection drugs used after transplant surgery are also risk factors.

How Does Basal Cell Nevus Syndrome Appear?

Basal cell nevus syndrome is developed chiefly on sun-exposed body parts like the head and neck. There can be changes in the skin, showing the following characteristics:

• A Shiny Bump: There is a translucent skin-colored bump on the skin. Tiny blood vessels are visible through this bump. This bump bleeds and might scab over.

• A Brown, Black, or Blue Lesion: There are lesions with dark spots with a translucent border.

• A Scaly Patch: There are flat patches with a raised edge. These patches might show growth.

• A White Lesion: These patches show a white, waxy appearance with no clearly defined border.

What Are the Signs of Basal Cell Nevus Syndrome?

The most common signs of basal cell nevus syndrome include:

• Basal cell carcinoma (the most common skin cancer) is often on the face, hands, or neck.

• The benign cysts of the maxilla and mandible appear during adolescence until age 30.

• Pits are found in the soles of feet or palms of hands.

Other symptoms include:

• Brain tumors, including meningioma or medulloblastoma.

• Cleft lip or palate.

• Eye-related disorders like crossed eyes (strabismus), small eyes (microphthalmia), cataracts, or rapid eye movements (nystagmus).

• Calcified ovaries (fibromas).

• Cardiac fibromas, cardiac arrhythmia.

• Large forehead (frontal bossing) or wide-set eyes (hypertelorism).

• Skeletal problems.

• Huge head (macrocephaly).

• White skin bumps or cysts (facial milia).

Is Basal Cell Nevus Syndrome Inherited?

Yes, basal cell nevus syndrome is inherited mostly. There are two conditions:

• Inherited: About seven in ten people with basal cell nevus syndrome inherited it.

• Spontaneous: About three in ten people had not inherited it.

How to Diagnose Basal Cell Nevus Syndrome?

A physical examination is done to rule out and diagnose basal cell nevus syndrome, followed by a blood test to check for gene mutations.

The following are the imaging techniques:

• MRI (magnetic resonance imaging).

• Ultrasound.

• X-rays use small doses of radiation. Radiations can increase the risk of basal cell carcinoma.

How to Treat Basal Cell Nevus Syndrome?

For the management of basal cell nevus syndrome, a multidisciplinary approach is used. A dermatologist is required to diagnose and treat basal cell carcinomas. Metastasis has also been seen in these patients.

• Pediatric patients must undergo annual skin screening by a dermatologist until the first basal cell carcinoma, followed by a screening at least every six months.

• Adults should undergo a check-up every four months.

• Several baseline examinations are suggested in pediatric patients. A baseline MRI (magnetic resonance imaging) scan of the brain (repeated yearly until eight years of age, then discontinued) is advised. Baseline jaw X-rays are repeated annually until the first jaw cyst, followed by every six months.

• Baseline spine X-rays at one year of age and repeat if symptomatic or per scoliosis protocol every six months.

• A baseline cardiac ultrasound is suggested in pediatric patients to check for cardiac fibromas.

• Females should have a pelvic ultrasound at menarche (when the menstrual cycle begins)to check for ovarian fibromas.

• Annual speech, vision, and hearing screenings and routine developmental screenings should be performed in pediatric patients with Gorlin syndrome.

• Patients should have a baseline MRI scan of the brain, genetic counseling, and possibly a psychological evaluation if needed. Jaw X-rays should be repeated if required, and an annual neurology evaluation should occur in patients with a history of medulloblastoma.

• In addition, pregnant patients must undergo a medical maternal-fetal assessment as there is a risk for the following conditions:

  • Hydrocephalus.
  • Microcephaly
  • Cardiac fibromas.

The following are the methods used for the treatment

• Electrodesiccation and curettage.

• Cryosurgery.

• Surgical excision.

• Mohs micrographic surgery (MMS).

• MMS in combination with CO2 laser treatment.

Topical treatment options include

• 5 percent 5-Fluorouracil.

• 5 percent Imiquimod.

• Photodynamic therapy.

• Vismodegib, an antagonist of the smoothened receptor and a hedgehog pathway inhibitor can be used to treat basal cell nevus syndrome.

What Is the Differential Diagnosis?

1. Bazex syndrome.

2. Fibrous papule of the face.

3. Melanocytic nevi.

4. Milia.

5. Pseudohypoparathyroidism.

6. Rombo syndrome.

7. Seborrheic keratosis.

8. Unilateral nevoid BCC with comedones.

Conclusion

Basal cell nevus syndrome is a rare genetic disorder. It increases the risk of skin cancer called basal cell carcinoma. It also can cause jaw cysts or minor dents in hands or feet. With proper management, people with basal cell nevus syndrome typically live a high quality of life. It can be inherited or a spontaneous mutation. Genetic mutation is the leading cause of the syndrome. Many surgical, radiological, and topical treatments treat basal cell nevus syndrome.