Continuing medical education
The group of epidermal nevus syndromes: Part I. Well defined phenotypes

https://doi.org/10.1016/j.jaad.2010.01.017Get rights and content

The epidermal nevus syndromes represent a group of distinct disorders that can be distinguished by the type of associated epidermal nevus and by the criterion of presence or absence of heritability. Well defined syndromes characterized by organoid epidermal nevi include Schimmelpenning syndrome, phacomatosis pigmentokeratotica, nevus comedonicus syndrome, angora hair nevus syndrome, and Becker nevus syndrome. The molecular basis of these disorders has so far not been identified. By contrast, the group of syndromes characterized by keratinocytic nevi comprises three phenotypes with a known molecular etiology in the form of CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, type 2 segmental Cowden disease, and fibroblast growth factor receptor 3 epidermal nevus syndrome (García-Hafner-Happle syndrome), whereas Proteus syndrome is still of unknown origin. From this overview, it is clear that a specific type of these disorders cannot be classified by the name “epidermal nevus syndrome” nor by the terms “organoid nevus syndrome” or “keratinocytic nevus syndrome.”

Learning objectives

After completing this learning activity, participants should be able to distinguish nine different epidermal nevus syndromes by their characteristic features, understand the practical significance of avoiding terms like “epidermal nevus syndrome” or “keratinocytic nevus syndrome” to define any specific entity within this group of disorders, and differentiate between nonhereditary traits and those bearing a genetic risk because of either Mendelian or non-Mendelian inheritance.

Section snippets

Well defined epidermal nevus syndromes characterized by organoid nevi

These ENSs are specified by the presence of epithelial nevi showing hyperplasia or structural changes of sebaceous glands or hair follicles (Fig 1).

Epidermal nevus syndromes characterized by keratinocytic nevi

These syndromes are defined by the presence of nonorganoid EN, showing differentiation exclusively to keratinocytes (Fig 1).

Synopsis of well defined epidermal nevus syndromes

Table VIII summarizes the distinguishing features of nine well defined ENSs. The molecular basis of three syndromes characterized by keratinocytic nevi has already been identified, whereas the origin of the ENSs specified by organoid nevi is so far unknown.

In my view, a biopsy specimen is not generally needed, but in cases of doubt this measure may be helpful to identify a sebaceous, Becker, or CHILD nevus. In cases of noninflammatory keratinocytic nevi, histopathologic examination may

References (288)

  • E.V. Bonioli et al.

    Sebaceous nevus syndrome: report of two cases

    Pediatr Neurol

    (1997)
  • S. Menascu et al.

    Linear nevus sebaceus syndrome: case reports and review of the literature

    Pediatr Neurol

    (2008)
  • B. Katz et al.

    Optic nerve hypoplasia and the syndrome of nevus sebaceus of Jadassohn. A new association

    Ophthalmology

    (1987)
  • D.E. Carey et al.

    Hypophosphatemic rickets/osteomalacia in linear sebaceous nevus syndrome: a variant of tumor-induced osteomalacia

    J Pediatr

    (1986)
  • F. Skovby et al.

    Hypophosphatemic rickets in linear sebaceous nevus sequence

    J Pediatr

    (1987)
  • L.C. Aschinberg et al.

    Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions

    J Pediatr

    (1977)
  • R.A. Daniels et al.

    Tumorous phosphaturic osteomalacia: report of a case associated with multiple hemangiomas of bone

    Am J Med

    (1979)
  • G. Amir et al.

    Widespread hemangiomatosis of bone associated with rickets: recovery after irradiation

    J Pediatr

    (1993)
  • M.C. Barkham et al.

    Should naevus sebaceus be excised prophylactically? A clinical audit

    J Plast Reconstr Aesthet Surg

    (2007)
  • B. Cribier et al.

    Tumors arising in nevus sebaceus: a study of 596 cases

    J Am Acad Dermatol

    (2000)
  • R. Happle

    What is a nevus? A proposed definition of a common medical term

    Dermatology

    (1995)
  • L.M. Solomon et al.

    The epidermal nevus syndrome

    Arch Dermatol

    (1968)
  • L.M. Solomon et al.

    Epidermal and other congenital organoid nevi

    Curr Probl Pediatr

    (1975)
  • R. Happle

    Epidermal nevus syndromes

    Semin Dermatol

    (1995)
  • J.L. Sugarman

    Epidermal nevus syndromes

    Semin Cutan Med Surg

    (2007)
  • L. Pavone et al.

    Epidermal nevus syndrome: a neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy

    Neurology

    (1991)
  • J.A. Hodge et al.

    The epidermal nevus syndrome

    Int J Dermatol

    (1991)
  • J.F. Meschia et al.

    Familial systematized epidermal nevus syndrome

    Am J Med Genet

    (1992)
  • T.A. Grebe et al.

    Further delineation of the epidermal nevus syndrome: two cases with new findings and literature review

    Am J Med Genet

    (1993)
  • F. Fantini et al.

    Extensive nevus comedonicus, congenital cataract and strabismus

    Eur J Dermatol

    (1995)
  • R. Kawachi et al.

    Epidermal nevus syndrome with hemangioma simplex

    J Dermatol

    (1997)
  • A.N. Abdelhalim et al.

    Epidermal nevus syndrome: megalencephaly with bihemispheric and cerebellar involvement: imaging and neuropathologic correlation

    J Comput Assist Tomogr

    (2003)
  • A. García-de-Jalón et al.

    Epidermal naevus syndrome (Solomon's syndrome) associated with bladder cancer in a 20-year-old female

    Scand J Urol Nephrol

    (2004)
  • R. Happle et al.

    Epidermal nevi

    Adv Dermatol

    (2002)
  • R.J. Gorlin et al.

    Syndromes of the head and neck

    (2001)
  • R. Happle

    Gustav Schimmelpenning and the syndrome bearing his name

    Dermatology

    (2004)
  • G.W. Schimmelpenning

    Klinischer Beitrag zur Symptomatologie der Phakomatosen

    Fortschr Röntgenstr

    (1957)
  • P.J. Gurecki et al.

    Developmental neural abnormalities and seizures in epidermal nevus syndrome

    Dev Med Child Neurol

    (1996)
  • W. Zhang et al.

    Neuroimaging features of epidermal nevus syndrome

    AJNR Am J Neuroradiol

    (2003)
  • D.J. Atherton et al.

    Naevi and other developmental defects

  • E.S. Kishida et al.

    Epidermal nevus syndrome associated with adnexal tumors, Spitz nevus, and hypophosphatemic vitamin D-resistant rickets

    Pediatr Dermatol

    (2005)
  • S. Chatproedprai et al.

    Epidermal nevus syndrome

    Int J Dermatol

    (2007)
  • K. Paley et al.

    Delayed diagnosis of epidermal nevus syndrome associated with substantial brain malformations: a case report and review of the literature

    Cutis

    (2008)
  • Y. Miyagawa et al.

    Epidermal nevus syndrome associated with anterior scleral staphyloma and ectopic bone and cartilaginous intraocular tissue

    Jpn J Ophthalmol

    (2010)
  • A. Murakami et al.

    Oral manifestations of Schimmelpenning syndrome: case report and review of literature

    Ann Acad Med Singapore

    (1999)
  • J. Wauschkuhn et al.

    Systematized sebaceous, pigmented and epithelial nevi with neurologic symptoms: Feuerstein-Mims' neuroectodermal syndrome

    Hautarzt

    (1971)
  • J. Brihaye et al.

    Late occurrence of additional ocular and intracranial pathologies in the linear nevus sebaceus (Feuerstein-Mims) syndrome

    Acta Neurochir

    (1988)
  • R. Moorjani et al.

    Feuerstein and Mims syndrome with resistant rickets

    Pediatr Radiol

    (1976)
  • O.P. Hornstein

    Knickenberg: Zur Kenntnis des Schimmelpenning-Feuerstein-Mims-Syndroms (Organoide Naevus-Phakomatose)

    Arch Dermatol Forsch

    (1974)
  • H.D. Schworm et al.

    Discordant monozygotic twins with the Schimmelpenning-Feuerstein-Mims syndrome

    Clin Genet

    (1996)
  • Cited by (180)

    • Phacomatosis spilosebacea: A new name for a distinctive binary genodermatosis

      2023, Journal of the American Academy of Dermatology
    • The Forgotten Phacomatoses: A Neuroimaging Review of Rare Neurocutaneous Disorders

      2022, Current Problems in Diagnostic Radiology
      Citation Excerpt :

      Supratentorial brain anomalies associated with rhombencephalosynapsis were also reported, including abnormal gyri, corpus callosal anomalies, large massa intermedia, thalamic fusion, and absent septum pellucidum.72 CHILD syndrome (MIM #308050) is characterized by unilateral skin inflammation with erythema and scaling and ipsilateral visceral and limb abnormalities, ranging from limb hypoplasia to complete limb absence.77 These findings constitute the basis of the acronym; Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects.78

    • Classification of and the latest photoelectric therapy for epidermal nevi

      2022, Chinese Journal of Plastic and Reconstructive Surgery
    • Schimmelpenning syndrome: A neuro-oculo-cutaneous disorder

      2023, Indian Dermatology Online Journal
    View all citing articles on Scopus

    Funding sources: None.

    Conflicts of interest: The authors, editors, JAAD CME council members, and peer reviewers have no relevant financial relationships.

    View full text