An epidermal nevus is a type of congenital hamartoma. This means it is a benign, non-cancerous overgrowth of the normal cells that make up the epidermis, the outermost layer of the skin. The term “nevus” is a general medical term for a birthmark or a mole.

To understand how an epidermal nevus forms, it is helpful to use an analogy.

• Think of the process of building a baby’s skin in the womb as laying down millions of identical, perfectly smooth “tiles” (the epidermal cells). This process follows a master blueprint contained in the DNA.
• In an epidermal nevus, very early in this construction process, one single tile receives a “faulty instruction”, a spontaneous genetic error, or mutation.
• This single faulty tile, and all the new tiles that are ever made by copying it, will now follow this new, slightly different blueprint.
• As the embryo grows, these cells migrate and multiply, creating a distinct patch or streak of “tiles” that are thicker, rougher, or more disorganized than the surrounding smooth tiles.
• This patch of different-looking tiles that often follows the normal lines of skin development is the epidermal nevus.

Because this genetic error occurred only in that one original skin cell, the rest of the “building” the rest of the skin and the body is made from the original, correct blueprint. This concept is known as mosaicism.

A key feature of many epidermal nevi is that they often follow a pattern known as the Lines of Blaschko. These are invisible lines in the skin that trace the path of embryonic skin cell migration. This is why the lesions often appear in a linear, swirled, or whorled pattern.

Clinically, it’s caused by a somatic mutation in skin cells during embryonic development, leading to localized overproliferation of keratinocytes or other skin components.

The cause of an epidermal nevus is a postzygotic somatic mutation.

• Somatic means the mutation occurs in a regular body cell, not in an egg or sperm cell.
• Postzygotic means the mutation occurs after fertilization, during the early stages of embryonic development.

This is a random genetic error. The specific genes that are mutated are often those that are part of key cellular signaling pathways that control cell growth and differentiation, such as the FGFR3, PIK3CA, or RAS family of genes. When one of these genes is mutated in a single embryonic skin cell, it causes that cell and all of its descendants to overgrow in a disorganized but benign fashion, forming the nevus.

In my experience, these lesions are typically not inherited. They arise spontaneously during fetal development and follow the lines of Blaschko on the skin.

An epidermal nevus is a congenital condition, meaning it is present at or shortly after birth. It is not contagious and cannot be acquired later in life.

The most crucial thing for parents to understand is that it is not an inherited condition in the traditional sense. Because the mutation occurs spontaneously in the embryo, it was not passed down from the parents. There is nothing a parent did or did not do to cause it. The risk of the parents having another child with the same condition is extremely low, no higher than that of the general population.

In my experience, most cases are isolated, but some are associated with syndromes such as epidermal nevus syndrome especially when neurologic or skeletal symptoms are present.

The signs and symptoms depend on whether the nevus is an isolated skin finding or part of a broader syndrome.

The Skin Lesion Itself

The primary sign is the appearance of the birthmark.

• Appearance: It is typically a skin-colored, brownish, or grayish patch. While it may be flat at birth, it often becomes thickened, warty (verrucous), and can have a velvety texture over time, especially during puberty.
• Pattern: The lesion often appears in a linear (straight line), whorled, or swirled pattern.
• Location: It can appear anywhere on the body, but it is common on the trunk, limbs, and head and neck.
• Symptoms: The nevus itself is usually asymptomatic. It does not typically cause pain, but it can sometimes be itchy. The primary concern is usually its cosmetic appearance.

The Association with Epidermal Nevus Syndrome (ENS)

The true medical significance of an epidermal nevus is its potential association with Epidermal Nevus Syndrome.

• ENS is not a single disease, but a broad term used to describe the combination of having an epidermal nevus along with abnormalities in other organ systems, most commonly the brain, skeleton, and eyes.
• The risk of having ENS is directly related to the size and extent of the nevus. A person with a small, isolated epidermal nevus is very unlikely to have any other problems. A person with a very large or extensive nevus, especially on the head or face, has a higher risk.
• The associated problems in ENS can include:
  • Neurological Issues: Seizures (epilepsy), developmental delays, or intellectual disability.
  • Skeletal Issues: Abnormalities of the bones in the limbs or spine (scoliosis).
  • Ocular (Eye) Issues: A variety of abnormalities, including growths on the eye or strabismus.

Clinically, I look for unilateral, well-demarcated lesions, and in rare cases, systemic involvement (e.g., seizures, eye defects) when evaluating for a syndrome.

The diagnosis of the skin lesion itself is typically straightforward and made by a dermatologist. The main focus of the diagnostic process is to determine if it is an isolated finding or part of a syndrome.

1. Clinical Examination: The diagnosis of an epidermal nevus is usually made based on its characteristic clinical appearance, a linear, warty plaque that has been present since birth.
2. Skin Biopsy: If the diagnosis is uncertain, a small sample of the lesion can be taken for a biopsy. A pathologist will examine the tissue under a microscope and can see the characteristic overgrowth of the epidermis, confirming the diagnosis. A biopsy can also be used for genetic testing of the affected tissue to identify the specific somatic mutation.

The Workup for Epidermal Nevus Syndrome

For any child with a large or extensive epidermal nevus, especially if it is located on the head or face, a comprehensive evaluation to screen for ENS is recommended. This evaluation should be coordinated by a team of specialists.

• A Full-Body Skin Examination by a dermatologist.
• A Neurological Examination by a pediatric neurologist. A brain MRI may be performed to look for any structural brain abnormalities.
• An Ophthalmological Examination by a pediatric ophthalmologist.
• A Skeletal Examination by an orthopedist, which may include X-rays.

In my experience, I assess associated anomalies especially in widespread or complex cases to rule out underlying syndromic presentations.

The management plan for an epidermal nevus has two distinct parts: treating the skin lesion itself (which is often cosmetic) and managing any associated problems if Epidermal Nevus Syndrome is diagnosed.

1. Treatment of the Epidermal Nevus Skin Lesion

It is important to understand that the nevus is benign and does not medically require treatment. The decision to treat the skin lesion is almost always for cosmetic reasons or if the nevus is in a location where it is frequently irritated. Treatment can be challenging, and recurrence is common.

• Topical Treatments: Medicated creams containing retinoids, vitamin D analogues, or keratolytics (which help to break down thick skin) can sometimes help to flatten the lesion and reduce its warty appearance, but they do not remove it.
• Destructive Methods: These methods aim to remove the surface of the nevus.
  • Laser Ablation: CO2 or erbium:YAG lasers can be used to vaporize the thickened epidermal tissue.
  • Cryotherapy: Using liquid nitrogen to freeze and destroy the tissue.
  • These methods often require multiple sessions and have a risk of scarring and recurrence.
• Surgical Excision: The most definitive treatment for an epidermal nevus is to surgically cut it out. This is a practical option for smaller nevi. For very large, extensive nevi, surgical excision would result in a significant scar and may require skin grafting, making it a more complex decision.

2. Management of Epidermal Nevus Syndrome

If a child is diagnosed with ENS, the management is entirely supportive and is tailored to their specific problems. This requires a multidisciplinary team of specialists.

• For Epilepsy: Treatment with anti-seizure medications managed by a neurologist.
• For Developmental Delays: An intensive program of early intervention therapies, including physical, occupational, and speech therapy.
• For Skeletal or Eye Problems: Management by an orthopedist or ophthalmologist as needed.
• An individualized education plan (IEP) is essential to support the child’s learning needs in school.

Clinically, treatment is tailored to the patient’s age, symptoms, and lesion location, persistent or extensive lesions may need long-term dermatologic follow-up.

An epidermal nevus is a benign, non-cancerous birthmark that results from a random genetic error in a single skin cell during fetal development. While the appearance of the linear, warty plaque can be a source of cosmetic concern, the skin lesion itself is harmless. Its true medical significance lies in its association with Epidermal Nevus Syndrome. A large or extensive nevus should be considered a clue that warrants a thorough evaluation by a team of specialists to screen for any underlying neurological, skeletal, or ocular issues. A comprehensive initial workup provides parents with crucial answers and peace of mind. It ensures that if any associated problems are present, they can be managed proactively, allowing a child to receive the support they need to thrive.

The American Academy of Dermatology (AAD). (n.d.). Birthmarks: Signs and symptoms. Retrieved from https://www.aad.org/public/diseases/a-z/birthmarks-symptoms

National Organization for Rare Disorders (NORD). (2022). Epidermal Nevus Syndrome. Retrieved from https://rarediseases.org/rare-diseases/epidermal-nevus-syndrome/

National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2021). Epidermal nevus. Retrieved from https://rarediseases.info.nih.gov/diseases/6334/epidermal-nevus