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Epidermal Nevus Syndrome

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
 
Updated: Jun 06, 2016
 

Background

Epidermal nevi (EN) are congenital hamartomas of embryonal ectodermal origin classified on the basis of their main component; the component may be sebaceous, apocrine, eccrine, follicular, or keratinocytic. An estimated one third of individuals with epidermal nevi have involvement of other organ systems; hence, this condition is considered to be an epidermal nevus syndrome (ENS). Solomon defines epidermal nevus syndrome as a sporadic neurocutaneous linkage of congenital ectodermal defects in the skin, brain, eyes, and/or skeleton. Epidermal nevus syndrome is often termed the Solomon syndrome. Schimmelpenning first detailed epidermal nevi with neurologic anomalies; hence, the term Schimmelpenning syndrome. The term organoid nevus may be used to emphasize the admixture of epidermal cells often evident in individual lesions of epidermal nevi.

Gustav Schimmelpenning, born in 1928 in Oldenburg (Germany), served from 1971-1994 as the head of the Department of Psychiatry at the University of Kiel.[1] In 1957, he described a case of sebaceous nevus involving the head, with ipsilateral ocular lesions including coloboma of the upper lid, increased density of cranial bones, epileptic seizures, and mental retardation. He called this combination of anomalies a new phacomatosis. Subsequently, others reported this phenotype as Schimmelpenning syndrome, Feuerstein-Mims syndrome, Schimmelpenning-Feuerstein-Mims syndrome, epidermal nevus syndrome, Solomon syndrome, linear sebaceous nevus (LSN) syndrome, organoid nevus phacomatosis, or Jadassohn nevus phacomatosis.

A clinical entity called epidermal nevus syndrome should be more precisely defined and distinguished by clinical, histopathologic, and genetic criteria. In this review, 4 distinct epidermal nevus syndromes, recognizable by the different types of associated epithelial nevi, are described. These include linear sebaceous nevus, linear nevus comedonicus (NC), linear epidermal nevus (LEN), and inflammatory linear verrucous epidermal nevus (ILVEN). Each type may be regarded as part of a syndrome with systemic associations.

Linear epidermal nevus syndrome is a congenital neurocutaneous disorder characterized by linear epidermal nevus with significant involvement of the nervous, ophthalmologic, and/or skeletal systems.[2] Clinical manifestations include mental retardation, seizures, and movement disorders that are caused by a wide range of neuropathologic lesions. Intracranial and/or intraspinal lipomas may occur.

Linear sebaceous nevus, also known as organoid nevus syndrome, often has the term linear deleted because almost all syndromic sebaceous nevi are linear. It has also been called Schimmelpenning-Feuerstein-Mims syndrome and Jadassohn nevus phakomatosis. Schimmelpenning syndrome, as noted above, links a sebaceous nevus with cerebral anomalies, coloboma, and lipodermoid of the conjunctiva.

Linear nevus comedonicus is also known as comedone nevus, nevus follicularis keratosus, nevus acneiformis unilateralis, and nevus zoniform. Cataracts may be a prominent feature of nevus comedonicus syndrome.

Inflammatory linear verrucous epidermal nevus is a linear, persistent, pruritic plaque, usually first noted on a limb in early childhood. Originally described by Unna in 1896, a few patients were reported prior to 1971 when Altman and Mehregan[3] delineated inflammatory linear verrucous epidermal nevus as a distinct entity in 25 patients. They coined the name inflammatory linear verrucous epidermal nevus, labeling it a clinical and histopathologic type of linear verrucous nevus that is often inflammatory or psoriasiform. Inflammatory linear verrucous epidermal nevus accounts for approximately 5% of patients with epidermal nevi and has been described in a mother and daughter.

Six different syndromes with epidermal nevi as part of them have been delineated. These include (1) Proteus, (2) congenital hemidysplasia with ichthyosiform nevus and limb defect, (3) phakomatosis pigmentokeratotica, (4) sebaceous nevus, (5) Becker nevus, and (6) nevus comedonicus[4] syndromes.

Phacomatosis pigmentokeratotica is characterized by the presence of multiple organoid nevi with sebaceous differentiation, a speckled lentiginous nevus, and skeletal and neurologic abnormalities.[5] It may or may not be associated with extracutaneous involvement. In a study of one affected family, phacomatosis pigmentokeratotica was found to be caused by a postzygotic HRAS mutation in a multipotent progenitor cell.[6]

The spectrum has recently been expanded with the description of linear Cowden nevus as a new distinct epidermal nevus.[7] This nonorganoid epidermal nevus is probably due to loss of heterozygosity, occurring at an early developmental stage in an embryo with a germline PTEN mutation, giving rise to Cowden disease. The combination of nevoid hypertrichosis, diffuse lipoatrophy, and epidermal nevus has been suggested as a possible new epidermal nevus syndrome.[8] Thus, the epidermal nevus syndrome may be best viewed as a heterogeneous congenital disorder that includes both the keratinocytic epidermal nevus syndrome and sebaceous nevus syndrome.[9] An individual patient may have the same postzygotic HRAS and KRAS gene mutations and be evident clinically with distinct features.

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Pathophysiology

Epidermal nevi arise from pluripotential germinative cells of the basal layer of the embryonic epidermis.

Inflammatory linear verrucous epidermal nevus is distinct from psoriasis; however, they may share some common pathogenic pathways. These pathways are probably mediated by interleukin 1, interleukin 6, tumor necrosis factor-alpha, and intercellular adhesion molecule-1.

Epidermal nevus syndrome–associated skeletal disease focal bone defects may manifest as fibrous dysplasia, even without the typical radiographic or histopathologic findings of fibrous dysplasia.[10] A patient had elevated circulating fibroblast growth factor 23 (FGF-23) levels with no activating mutations. This focal skeletal disease may be a source of FGF-23 in persons with epidermal nevus syndrome and thus may be a clue to its pathogenesis.

A bilateral, systematized epidermal nevus syndrome patient was described with cerebral involvement caused by a mosaic FGFR3 mutation, possibly representing a distinct entity within the group of epidermal nevus syndromes.[11] Other mutations of FGFR3 have been described in keratinocytic epidermal nevus syndrome.[12] A mosaic KRAS mutation has also been documented.[13]

The Schimmelpenning-Feuerstein-Mims syndrome, which is composed of a craniofacial nevus sebaceus, seizures, developmental delay, and ocular and skeletal abnormalities, is a sporadic condition hypothesized to result from mosaicism involving a lethal autosomal dominant gene.[14] It has been described in severely affected discordant monozygotic twins, supporting the concept of a postzygotic mutation.

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Epidemiology

Frequency

The syndromes are uncommon. In a review by Rogers and associates[15] of 131 patients with epidermal nevi and epidermal nevus syndrome, one third of the patients had the nevus sebaceous type, 60% had the noninflammatory type, 6% had inflammatory linear verrucous epidermal nevus, and only 2 had nevus comedonicus.

Sex

Linear sebaceous nevus syndrome and nevus comedonicus syndrome have a female-to-male ratio of 1:1. This ratio may also be true of linear epidermal nevus.

Inflammatory linear verrucous epidermal nevus has a female predominance, with a female-to-male ratio of 4:1.

Age

The age at diagnosis ranges from birth to age 40 years.

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Prognosis

The prognosis depends on the presence and the severity of any of a variety of associated internal defects. Mortality and morbidity are related to the associated systemic anomalies.

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Patient Education

The patient and/or the family should be reassured that epidermal nevus syndrome is not a genetic disorder that can be passed to future children.

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Sergiusz Jozwiak, MD, PhD Professor and Head of Pediatric Neurology, Warsaw Medical University, Poland

Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi

Disclosure: Received honoraria from Novartis for speaking and teaching.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Mark A Crowe, MD Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine

Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society

Disclosure: Nothing to disclose.

References
  1. Happle R. Gustav Schimmelpenning and the syndrome bearing his name. Dermatology. 2004. 209(2):84-7. [Medline].

  2. Mall V, Heinen F, Uhl M, Wellens E, Korinthenberg R. CNS lipoma in patients with epidermal nevus syndrome. Neuropediatrics. 2000 Aug. 31(4):175-9. [Medline].

  3. Altman J, Mehregan AH. Inflammatory linear verrucose epidermal nevus. Arch Dermatol. 1971 Oct. 104(4):385-9. [Medline].

  4. Vidaurri-de la Cruz H, Tamayo-Sanchez L, Duran-McKinster C, de la Luz Orozco-Covarrubias M, Ruiz-Maldonado R. Epidermal nevus syndromes: clinical findings in 35 patients. Pediatr Dermatol. 2004 Jul-Aug. 21(4):432-9. [Medline].

  5. Chantorn R, Shwayder T. Phacomatosis pigmentokeratotica: a further case without extracutaneous anomalies and review of the condition. Pediatr Dermatol. 2011 Nov-Dec. 28(6):715-9. [Medline].

  6. Groesser L, Herschberger E, Sagrera A, Shwayder T, Flux K, Ehmann L, et al. Phacomatosis Pigmentokeratotica Is Caused by a Postzygotic HRAS Mutation in a Multipotent Progenitor Cell. J Invest Dermatol. 2013 Jan 21. [Medline].

  7. Happle R. Linear Cowden nevus: a new distinct epidermal nevus. Eur J Dermatol. 2007 Mar-Apr. 17(2):133-6. [Medline].

  8. Bakhach M, Abbas O, Kibbi AG, Kurban M, Jundi MA. Nevoid hypertrichosis, diffuse lipoatrophy and epidermal nevus: a new syndrome?. Int J Dermatol. 2013 Mar 3. [Medline].

  9. Igawa S, Honma M, Minami-Hori M, Tsuchida E, Iizuka H, Ishida-Yamamoto A. Novel postzygotic KRAS mutation in a Japanese case of epidermal nevus syndrome presenting with two distinct clinical features, keratinocytic epidermal nevi and sebaceous nevi. J Dermatol. 2016 Jan. 43 (1):103-4. [Medline].

  10. Heike CL, Cunningham ML, Steiner RD, et al. Skeletal changes in epidermal nevus syndrome: does focal bone disease harbor clues concerning pathogenesis?. Am J Med Genet A. 2005 Dec 1. 139A(2):67-77. [Medline].

  11. Garcia-Vargas A, Hafner C, Perez-Rodriguez AG, et al. An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation. Am J Med Genet A. 2008 Sep 1. 146A(17):2275-9. [Medline].

  12. Ousager LB, Bygum A, Hafner C. Identification of a novel S249C FGFR3 mutation in a keratinocytic epidermal nevus syndrome. Br J Dermatol. 2012 Jan 9. [Medline].

  13. Farschtschi S, Mautner VF, Hollants S, Hagel C, Spaepen M, Schulte C, et al. Keratinocytic epidermal nevus syndrome with Schwann cell proliferation, lipomatous tumour and mosaic KRAS mutation. BMC Med Genet. 2015 Feb 10. 16(1):6. [Medline]. [Full Text].

  14. Rijntjes-Jacobs EG, Lopriore E, Steggerda SJ, Kant SG, Walther FJ. Discordance for Schimmelpenning-Feuerstein-Mims syndrome in monochorionic twins supports the concept of a postzygotic mutation. Am J Med Genet A. 2010 Nov. 152A(11):2816-9. [Medline].

  15. Rogers M, McCrossin I, Commens C. Epidermal nevi and the epidermal nevus syndrome. A review of 131 cases. J Am Acad Dermatol. 1989 Mar. 20(3):476-88. [Medline].

  16. Ball EA, Hussain M, Moss AL. Squamous cell carcinoma and basal cell carcinoma arising in a naevus sebaceous of Jadassohn: case report and literature review. Clin Exp Dermatol. 2005 May. 30(3):259-60. [Medline].

  17. Wu ZW, Shi WM, Sun Y, Li XJ, Song J. Cutaneous spindle cell squamous cell carcinoma in nevus sebaceous. Int J Dermatol. 2010 Dec. 49(12):1429-31. [Medline].

  18. Liu Y, Valdebran M, Chen J, Elbendary A, Wu F, Xu M. Nevus Sebaceous of Jadassohn With Eight Secondary Tumors of Follicular, Sebaceous, and Sweat Gland Differentiation. Am J Dermatopathol. 2016 Apr 19. [Medline].

  19. Miyagawa Y, Nakazawa M, Kudoh T. Epidermal nevus syndrome associated with anterior scleral staphyloma and ectopic bone and cartilaginous intraocular tissue. Jpn J Ophthalmol. 2010 Jan. 54(1):15-8. [Medline].

  20. Menni S, Boccardi D, Gualandri L. Keratinocytic epidermal nevus with oral involvement and cleft palate. G Ital Dermatol Venereol. 2008 Oct. 143(5):347-9. [Medline].

  21. Castori M, Annessi G, Castiglia D, et al. Systematized organoid epidermal nevus with eccrine differentiation, multiple facial and oral congenital scars, gingival synechiae, and blepharophimosis: a novel epidermal nevus syndrome. Am J Med Genet A. 2010 Jan. 152A(1):25-31. [Medline].

  22. Happle R. Epidermal nevus syndromes. Semin Dermatol. 1995 Jun. 14(2):111-21. [Medline].

  23. Mahto M, Ashworth J, Vickers DM. A case of linear epidermal naevus presenting as genital warts--a cautionary tale. Int J STD AIDS. 2005 Mar. 16(3):267-9. [Medline].

  24. Wiedemeyer K, Hartschuh W. Trichoblastomas with Merkel cell proliferation in nevi sebacei in Schimmelpenning-Feuerstein-Mims syndrome - Histological differentiation between trichoblastomas and basal cell carcinomas. J Dtsch Dermatol Ges. 2009 Feb 2. [Medline].

  25. Idriss MH, Elston DM. Secondary neoplasms associated with nevus sebaceus of Jadassohn: a study of 707 cases. J Am Acad Dermatol. 2014 Feb. 70(2):332-7. [Medline].

  26. Pernet C, Munoz J, Bessis D. [PENS (papular epidermal nevus with "skyline" basal cell layer)]. Ann Dermatol Venereol. 2015 Jan. 142(1):41-5. [Medline].

  27. Jaqueti G, Requena L, Sanchez Yus E. Trichoblastoma is the most common neoplasm developed in nevus sebaceus of Jadassohn: a clinicopathologic study of a series of 155 cases. Am J Dermatopathol. 2000 Apr. 22(2):108-18. [Medline].

  28. Micali G, Nasca MR, Musumeci ML. Effect of topical calcipotriol on inflammatory linear verrucous epidermal nevus. Pediatr Dermatol. 1995 Dec. 12(4):386-7. [Medline].

  29. Zvulunov A, Grunwald MH, Halvy S. Topical calcipotriol for treatment of inflammatory linear verrucous epidermal nevus. Arch Dermatol. 1997 May. 133(5):567-8. [Medline].

  30. Davison SP, Khachemoune A, Yu D, Kauffman LC. Nevus sebaceus of Jadassohn revisited with reconstruction options. Int J Dermatol. 2005 Feb. 44(2):145-50. [Medline].

  31. Winston KR, Kang J, Laoprasert P, Kleinschmidt-DeMasters BK. Hemispherectomy in a premature neonate with linear sebaceous nevus syndrome. Pediatr Neurosurg. 2008. 44(2):159-64. [Medline].

  32. Kiedrowicz M, Kacalak-Rzepka A, Królicki A, Maleszka R, Bielecka-Grzela S. Therapeutic effects of CO2 laser therapy of linear nevus sebaceous in the course of the Schimmelpenning-Feuerstein-Mims syndrome. Postepy Dermatol Alergol. 2013 Oct. 30(5):320-3. [Medline]. [Full Text].

  33. Shahgholi E, Mollaian M, Haghshenas Z, Honarmand M. Congenital rhabdomyosarcoma, central precocious puberty, hemihypertrophy and hypophosphatemic rickets associated with epidermal nevus syndrome. J Pediatr Endocrinol Metab. 2011. 24(11-12):1063-6. [Medline].

  34. Hato N, Tsujimura M, Takagi T, Okada M, Gyo K, Tohyama M, et al. Infantile inflammatory pseudotumor of the facial nerve as a complication of epidermal nevus syndrome with cholesteatoma. Auris Nasus Larynx. 2013 Feb 19. [Medline].

  35. Lefkowitz A, Schwartz RA, Lambert WC. Nevus comedonicus. Dermatology. 1999. 199(3):204-7. [Medline].

  36. Miteva LG, Dourmishev AL, Schwartz RA. Inflammatory linear verrucous epidermal nevus. Cutis. 2001 Nov. 68(5):327-30. [Medline].

 
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Characteristic epidermal nevus in the axillary fossa of a child with Jadassohn nevus phakomatosis.
An extensive plaque is observed over most of the left scapula, neck area, and lumbosacral location.
Plaque is evident in the region of the left groin, and it has a unilateral distribution.
Epidermal nevus syndrome, demonstrating extension of a plaque distally.
Extensive unilateral linear epidermal nevi in a 14-year-old girl with Jadassohn nevus phakomatosis. The plaques are elevated; some have verrucous characteristics.
An 8-year-old girl with Jadassohn nevus syndrome. Note typical plaques in the midline and on the arm and the neck. The plaques are darker and more verrucous on the arm and the neck than on the midline.
 
 
 
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