Epidermal nevus syndrome

Overview

Epidermal nevus syndrome (ENS) refers to a group of rare, congenital disorders characterized by the presence of epidermal nevi (noncancerous skin growths) along with abnormalities in other organ systems, including the nervous, skeletal, ocular, and urogenital systems. The syndrome represents a form of mosaicism, where some cells in the body carry a genetic mutation while others do not. ENS typically becomes apparent in infancy or early childhood, and its severity and symptoms vary widely depending on the organs involved.

Causes

Epidermal nevus syndrome is caused by postzygotic (after fertilization) somatic mutations, meaning the mutation occurs in some but not all of the body’s cells. The most commonly associated gene mutations include:

• FGFR3 (Fibroblast Growth Factor Receptor 3)

• HRAS and KRAS: Proto-oncogenes involved in cell signaling and development

• PTCH1: Associated with basal cell nevus syndrome-like features

Since these mutations occur sporadically, ENS is generally not inherited. However, the exact mutation and affected pathways can influence the type and severity of systemic involvement.

Symptoms

ENS presents with a combination of skin lesions and multisystem involvement. Symptoms may include:

Skin-related:

• Linear or patchy epidermal nevi—wart-like, brownish or skin-colored lesions following the lines of Blaschko

• Nevi may be present at birth or appear within the first year of life

• Lesions may become thickened or inflamed over time

Neurological:

• Seizures

• Intellectual disability or developmental delays

• Brain malformations (e.g., hemimegalencephaly)

• Hydrocephalus

Skeletal:

• Asymmetrical limb growth

• Shortened or malformed limbs

• Vertebral anomalies, scoliosis

Ocular:

• Colobomas (defects in the eye structure)

• Cataracts

• Optic nerve atrophy

Other possible symptoms:

• Heart or kidney malformations

• Genitourinary anomalies

Diagnosis

Diagnosis is based on clinical evaluation and a combination of skin, neurological, and radiological findings. Steps may include:

• Dermatological exam: Identification of epidermal nevi in characteristic distribution patterns

• Skin biopsy: Confirms the diagnosis and can help differentiate from other types of nevi

• Neuroimaging: MRI or CT scan of the brain to detect malformations

• Skeletal X-rays: To evaluate for bone anomalies

• Ophthalmologic evaluation: For vision-related issues

• Genetic testing: May identify mosaic mutations in affected tissue

Treatment

Treatment of ENS is symptomatic and multidisciplinary, aiming to manage skin lesions and systemic complications. Options include:

• Topical treatments: Retinoids or keratolytic agents for thickened skin lesions

• Laser therapy: May reduce the appearance of nevi or remove superficial lesions

• Surgical excision: Considered in cases of large or symptomatic nevi

• Antiepileptic medications: For seizure control

• Developmental therapy: Occupational and speech therapy for developmental delays

• Orthopedic interventions: For skeletal abnormalities or functional limitations

• Regular follow-ups: With neurology, dermatology, orthopedics, and ophthalmology as needed

Prognosis

The prognosis for individuals with epidermal nevus syndrome varies widely based on the extent of systemic involvement. Some children may have only mild skin lesions with little or no additional symptoms, while others may experience significant neurological or developmental challenges. With early diagnosis, comprehensive medical care, and supportive therapies, many individuals can lead improved and functional lives. Lifelong monitoring and care are typically necessary due to the potential for progression or complications over time.