Epidermal Nevus syndromes

Are You Confident of the Diagnosis?

Characteristic findings on physical examination

The epidermal nevus syndrome encompasses a heterogeneous group of disorders characterized by wide-spread whorls or bands of epidermal or appendageal cell types associated with one or more systemic abnormalities, with the central nervous system, eyes, and skeleton being most frequently involved. The cutaneous lesions for the most part, follow the lines of Blashcko, which are thought to represent patterns of ectodermal migration during embryogenesis (Figure 1).

Figure 1.

Widespread whorls of velvety tan papules characterize this systematized epidermal nevus of the ENS.

The epidermal nevus syndrome has been classified by Happle into two categories, those with keratinocytic proliferations and those with organoid lesions that stem from appendageal structures.

Who is at Risk for Developing this Disease?

Most epidermal nevus syndromes occur sporadically and are found in all ethnic or racial groups.

What is the Cause of the Disease?

Cutaneous lesions represent postzygotic somatic cell genetic mosaicism in most instances. Some well-defined syndromes have been characterized by known gene defects.


Pathophysiology for most syndromes is unknown. However genetic defects for some well-recognized conditions have recently been discovered. They include: ENS with epidermolyitic hyperkeratosis (K1 or K10), Type 2 segmental Cowden disease (PTEN), Garcia-Hafner-Happle ENS( FGFR3), CHILD syndrome (NSDHL),

Systemic Implications and Complications

There are both similarities and characteristic differences in systemic manifestations of the various epidermal nevus (EN) syndromes.

Nevus sebaceous syndrome patients may have skeletal, neurologic and ophthalomologic defects (Figure 2). They include hemimegalencephaly and other structural brain abnormalities, seizures, and mental retardation; craniofacial defects, kyphoscoliosis, hip dislocation, limb deformities and hypophosphatemic rickets; epibulbar lipodermoids, colobomas, corneal opacities and optic nerve defects

Figure 2.

A patient with the nevus sebaceous syndrome.

Phakomatosis pigmentokeratotica patients demonstrate a nevus spilus with the epidermal nevus, an example of twin spotting. They may have hyperhidrosis, muscular weakness, dysesthesia and sensory-motor neuropathy. Vitamin D resistant rickets is also more common in this ENS type.

Patients with the Becker nevus syndrome have patches that do not conform to the lines of Blaschko, but occur in a checkerboard pattern. These cases may have ipsilateral breast hypoplasia, supernumerary nipples, pectus deformities, fused ribs, short limbs, odontomaxillary hypoplasia and ipsilateral muscle hypoplasia.

Proteus syndrome is characterized by a nonorganoid soft, velvety EN accompanied by a progressive cerebriform plantar or palmar connective tissue nevus, telangiectatic vascular malformations, lipomas, bone overgrowth (particularly macrodactyly), seizures, mental retardation, and visceral overgrowth.

Type 2 segmental Cowden disease patients demonstrate hemihypertrophy, various hemolymphatic vascular malformations, cutaneous and systemic lipomatosis, hydrocephalus, seizures, gastrointestinal polyposis and focal segmental glomerulosclerosis

Treatment Options

Treatment options are summarized in Table I.

Table I.
Surgical options Medical options
 Selective focal areas for surgical excision  Keratolytic agents (eg, salicylic acid gel 6%) plus debridement
 Ablative CO2 laser vaporization  Topical retinoids (eg, tretinoin 0.1% cream, tazarotene (0.1% gel)
 Aggressive cryotherapy  Topical calcipotriene

Optimal Therapeutic Approach for this Disease

Surgical excision of cutaneous lesions that may be problematic should be considered prior to school age. This is particularly true for patient with lesions in the axillary and inguinal regions since thickening of lesions in those areas before puberty is not uncommon (ptychotrophism). Clearly, any tumors that arise need to be removed.

Keratolytic agents such as salicylic acid gel 6% followed by gentle debridement may be utilized to reduce stratum corneum thickness. Topical retinoids (such as tretinoin 0.1% cream or tazarotene 0.1% gel) or topical calcipotriene may be beneficial.

Patient Management

A multispecialty approach to patients with ENS is best. Neurology, ophthalmology, orthopedics, and later plastic surgery should provide assessments. Selective radiologic imaging will be necessary and may include magnetic resonance imaging and computed tomography of the craniospinal axis.

Unusual Clinical Scenarios to Consider in Patient Management

Patients with extensive EN should have serum calcium, phosphorus, and parathyroid hormone levels monitored for several years, until normal values are obtained on multiple occasions. Patients with Proteus syndrome need frequent surgical evaluation and follow-up. Periodic developmental and psychological assessments are necessary.

What is the Evidence?

Happle, R. “The group of epidermal nevus syndromes: Part I. Well defined phenotypes”. J Am Acad Dermatol. vol. 63. 2010. pp. 1-22. (This is an extensive review of the most common epidermal nevus syndromes.)

Happle, R. “The group of epidermal nevus syndromes: Part II. Less well defined phenotypes”. J Am Acad Dermatol. vol. 65. 2010. pp. 25-30. (This is an extensive review of the more unusual epidermal nevus syndromes.)

Branding-Bennett, HA, Morel, KD. “Epidermal nevi”. Pediatr Clin N Am. vol. 57. 2010. pp. 1184-98. (This is an excellent review of current knowledge of epidermal nevus syndromes.)