The epidermal nevus syndrome is known by many names. It is a multisystem disease with potentially devastating consequences. Most cases are sporadic though occasional cases of autosomal dominant transmission have been documented. Recent classifications have identified at least 5 distinct syndromes within this larger syndrome
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
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EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Schimmelpenning syndrome
Feuerstein and Mims syndrome
AGE RANGE-MEDIAN Birth to 40 years SEX (M:F) =
DISEASE ASSOCIATIONS CHARACTERIZATION Skeletal Findings Bone cysts
Bone hyperplasia or hypertrophy
Syndactyly, polydactyly, chinodactyly
Vitamin D-resistant rickets
Neurologic Findings Cerebrovascular accidents
Cerebrovascular malformations and neoplasias
Cranial nerve palsies
Spinal cord stenosis
9-30% of patients
Blocked tear duct
Colobomas of lid, iris, choroid retina
Corneal opacity and pannus formation
Ectopic lacrimal glands
Extension of epidermal nevus to eyelid, conjunctiva, or sclera
Micro- or macroophthalmia
Optic nerve hypoplasia
Urogenital Findings Horseshoe kidneys
Vascular Findings Aneurysms
Patent ductus arteriosus
Extensive linear epidermal nevus associated with hemangiomas of bones and vitamin-D-resistant rickets.
Stosiek N, Hornstein OP, Hiller D, Peters KP.
Department of Dermatology, University of Erlangen-Nuremberg, Germany.
Dermatology 1994;189(3):278-82 Abstract quote
The association of connate, left-sided, extensive epidermal verrucous nevus, multiple isolated bone tumors and vitamin-D-resistant rickets since childhood seen in a 20-year-old male patient corresponded to an epidermal nevus syndrome (ENS).
However, other organ involvement occasionally associated with ENS could not be found in this patient, and his intraosseous tumors represented histologically benign hemangiomas. Serum analysis revealed hypophosphatemia (together with phosphaturia), decreased levels of 1,25-dihydroxycholecalciferol and elevated levels of alkaline phosphatase indicating hypophosphatemic osteomalacia.
Therefore we suppose that vitamin-D-resistant rickets combined with skeletal tumors represents a peculiar type of osteomalacia caused by unilateral mesenchymomas.
Epidermal nevus syndrome: association with central precocious puberty and woolly hair nevus.
Tay YK, Weston WL, Ganong CA, Klingensmith GJ.
Department of Dermatology, University of Colorado Health Sciences Center, Denver 80262, USA.
J Am Acad Dermatol 1996 Nov;35(5 Pt 2):839-42 Abstract quote
The epidermal nevus syndrome is characterized by the association of epidermal nevi with abnormalities of the skin, skeletal system, central nervous system, eyes, and cardiovascular system, as well as with malignant conditions.
We describe a 2-year-old girl with an extensive epidermal nevus involving the left side of the body (nevus unius lateris) and associated with a woolly hair nevus on the left parietal area of the scalp and multiple acquired melanocytic nevi. Idiopathic central precocious puberty characterized by premature breast and public hair development and advanced bone age developed at the age of 20 months. A sharp increase in serum gonadotropins after a luteinizing hormone releasing hormone (LHRH) stimulation test confirmed the presence of central precocious puberty.
This is the third reported case of precocious puberty associated with the epidermal nevus syndrome.
Hypophosphatemic vitamin D-resistant rickets, precocious puberty, and the epidermal nevus syndrome.
Ivker R, Resnick SD, Skidmore RA.
Department of Dermatology, University of North Carolina at Chapel Hill, USA.
Arch Dermatol 1997 Dec;133(12):1557-61 Abstract quote
BACKGROUND: The association of multisystem pathologic conditions and epidermal nevi, known as the epidermal nevus syndrome, includes disorders of bone, central nervous system, eye, kidney, vasculature, body symmetry, and skin. Rarely, vitamin D-resistant rickets has been observed in association with this syndrome. Precocious puberty is another rare finding associated with epidermal nevus syndrome, having been observed in 3 patients.
OBSERVATION: A female infant with an extensive epidermal nevus, hypophosphatemia, and precocious puberty is described. Despite medical therapy, the patient's phosphate levels continued to be very low (0.87-0.97 mmol/L), establishing the diagnosis of hypophosphatemic vitamin D-resistant rickets. At 21 months of age, areas of the nevus were excised. Laboratory values obtained shortly after the operation showed a significant, but transient, improvement in the serum phosphate level. After a second excision, maintenance of her serum phosphate level in the range of 1.29 to 1.61 mmol/L was possible.
CONCLUSIONS: There is evidence that epidermal nevi produce a potent phosphaturic factor. We hypothesize that limited excision debulked the nevus sufficiently to allow medical management of the hypophosphatemia. Surgical intervention should be considered for patients affected with vitamin D-resistant rickets with epidermal nevi. The cause of the precocious puberty is unknown. It may be hypothesized that the nevus released a factor that induced puberty.
A novel epidermal nevus syndrome with congenital cylindromatous turban tumor.
Department of Pathology, University of Miami School of Medicine, Miami, FL, USA.
J Cutan Pathol. 2003 Oct;30(9):586-90 Abstract quote.
BACKGROUND: Epidermal nevi (in the broad sense of epithelial nevi) may give rise to benign or malignant skin tumors. They may also be associated with anomalies of other organ systems in an epidermal nevus syndrome.
RESULTS: This article describes a preterm infant with nevus sebaceus of the scalp and face, a large turban tumor with features of malignant cylindroma and multiple non-cutaneous defects. These included skeletal, hematopoietic, hepatobiliary, and urinary anomalies. Severe secondary lesions were present (pulmonary hypoplasia due to oligohydramnios; cerebral infarcts probably related to the turban tumor). Karyotype was normal, and family history was negative.
CONCLUSIONS: This unique case is unlike any reported epidermal nevus syndrome. Similarly, there is no prior report of a congenital cylindroma, certainly not as a turban tumor, which implies very rapid growth. The presence of both overgrowth and undergrowth phenomena (e.g. hypoplastic urinary tract and biliary atresia) may reflect dysregulation of paracrine growth factors, presumably due to genetic mutation.
Chromosomal mosaicism in two patients with epidermal verrucous nevus. Demonstration of chromosomal breakpoint.
Stosiek N, Ulmer R, von den Driesch P, Claussen U, Hornstein OP, Rott HD.
Department of Dermatology, University of Erlangen-Nuremberg, Germany.
J Am Acad Dermatol 1994 Apr;30(4):622-5 Abstract quote
Linear epidermal nevi are hamartomas that originate in embryonic ectoderm. For epidermal nevi associated with involvement of other systems, such as the skeleton or central nervous system, the term epidermal nevus syndrome has been introduced. Chromosomal aberrations have been suggested but not proven as an underlying cause.
We performed cytogenetic studies of skin cells from two unrelated men who had a verruciform epidermal nevus. Variegated translocation mosaicism with an identical breakpoint localized at the long arm of chromosome 1 was present in both patients. Normal skin and blood lymphocytes showed normal karyotypes.
Epidermal nevus syndrome: MR of intracranial involvement.
Lazzeri S, Mascalchi M, Cellerini M, Martinetti MG, Dal Pozzo G.
Dipartimento di Fisiopatologia Clinica, Universita di Firenze, Italy.
AJNR Am J Neuroradiol 1993 Sep-Oct;14(5):1255-7 Abstract quote
Focal thickening of the calvarium, hypoplasia of the white matter, cortical calcifications, and a leptomeningeal drape that enhanced after contrast injection were demonstrated by MR in the parietooccipital region ipsilateral to a facial sebaceous nevus in a patient with epidermal nevus syndrome.
Epidermal nevi and the epidermal nevus syndrome. A review of 131 cases.
Rogers M, McCrossin I, Commens C.
Department of Dermatology, Children's Hospital, South Wales, Australia.
J Am Acad Dermatol 1989 Mar;20(3):476-88 Abstract quote
One hundred thirty-one patients with epidermal nevi are reviewed. The commonest site of involvement was the head and neck, and 13% of patients had widespread lesions. Ages of onset ranged from birth to 14 years. A spread beyond the original distribution was noted in 37% of patients. Many clinical patterns occurred, including eight cases of inflammatory linear verrucous epidermal nevus. A variety of other cutaneous abnormalities were found. Biopsies were performed in 41 cases. Three patients developed secondary tumors. One hundred nineteen of the patients were assessed for the presence of abnormalities in other organ systems. One or more abnormalities were demonstrated in 33% of patients, and in 5%, five or more abnormalities were detected.
This study indicates that patients with epidermal nevi are at significant risk of having other abnormalities and warrant detailed initial assessment and close follow-up.
Epidermal nevus syndrome: subgroup with neuronal migration defects.
el-Shanti H, Bell WE, Waziri MH.
Department of Pediatrics, University of Iowa College of Medicine, Iowa City.
J Child Neurol 1992 Jan;7(1):29-34 Abstract quote
Epidermal nevus syndrome is one of the sporadic congenital hamartoses in which neurologic abnormalities have been frequently reported.
We report two cases with severe primary brain involvement, seizures, mental retardation, and facial hemihypertrophy. We emphasize the superiority of magnetic resonance imaging over other radiographic studies in outlining the primary central nervous system anomalies associated with this syndrome. Although attempts were made to distinguish between several variants of epidermal nevus syndrome, it is clear that these are one entity. Proteus syndrome, encephalocraniocutaneous lipomatosis, and epidermal nevus syndrome have several overlapping phenotypic features.
We suggest that they represent a phenotypic continuum, which in turn suggests a common pathogenetic process. While the cause of these syndromes is unknown, observations point to a somatic mutation leading to variable patterns of mosaicism.
Semin Dermatol 1995;14:111 Shimmelpenning syndrome
Nevus comedonicus syndrome
Pigmented hairy epidermal nevus syndrome Paradominant inheritance
Becker's nevus, ipsilateral breast hypoplasia, skeletal defects
Proteus syndrome Paradominant inheritance
Soft, flat, nonorganoid epidermal nevus
Anomalies of brain, heart, or kidney
Familial systematized epidermal nevus syndrome.
Meschia JF, Junkins E, Hofman KJ.
Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Am J Med Genet 1992 Nov 15;44(5):664-7 Abstract quote
Epidermal nevi are typically congenital but rarely familial.
We report on a family in which 3 relatives have systematized epidermal nevi. The propositus also has evidence of a hemangioma and a hemangioendothelioma. Peripheral blood and skin fibroblast karyotypes of the propositus did not show evidence of mosaicism. Epidermal nevi have been associated with nondermatologic pathology, involving the nervous, vascular, and skeletal systems in sporadic cases.
This report demonstrates that nondermatologic pathology can be also be associated with systematized epidermal nevi in a familial setting. The apparent skipping of generations may be explained by autosomal dominant inheritance with decreased penetrance.
Further delineation of the epidermal nevus syndrome: two cases with new findings and literature review.
Grebe TA, Rimsza ME, Richter SF, Hansen RC, Hoyme HE.
Department of Pediatrics, Steele Memorial Children's Research Center, Tucson, AZ
Am J Med Genet 1993 Aug 1;47(1):24-30 Abstract quote
"Epidermal nevus syndrome" ("ENS") is a neurocutaneous disorder in which epidermal nevi are associated with other abnormalities, most commonly of the skeletal and central nervous systems.
We present two cases of epidermal nevus syndrome (ENS) with very different clinical findings. The first case is a newborn with multiple linear epidermal nevi of the trunk and limbs, and several other anomalies, including bony duplications of the lower limbs and hypoplastic left heart syndrome. The second patient, a 6-year-old boy, has a linear nevus sebaceous of the scalp with severe CNS involvement, including generalized seizures, moderate mental retardation, microcephaly, and a left hemiparesis. He also has genitourinary, cardiac, and skeletal defects. These two patients exhibit several abnormalities not previously recognized and illustrate the wide clinical spectrum of "epidermal nevus syndrome."
We present a review of the clinical findings in 74 cases of "ENS." Correlation was noted between the presence of skin lesions located on the head and CNS involvement. The wide clinical spectrum of "ENS" as illustrated by these two patients suggests that "ENS" is a causally heterogeneous group of disorders.
Phacomatosis pigmentokeratotica: another epidermal nevus syndrome and a distinctive type of twin spotting.
Boente MC, Pizzi de Parra N, Larralde de Luna M, Bonet HB, Santos Munoz A, Parra V, Gramajo P, Moreno S, Asial RA.
Department of Dermatology, Hospital del Nino Jesus, Pasaje Bertres 224, San Miguel de Tucuman, 4000 Tucuman, Argentina.
Eur J Dermatol 2000 Apr-May;10(3):190-4 Abstract quote
The name epidermal nevus syndrome could be applied to a group of clinically and histopathologically different entities as has been pointed out by Happle. Phacomatosis pigmentokeratotica is a further type of epidermal nevus syndrome distinguished by the presence of a sebaceous nevus and a contralateral speckled lentiginous nevus of the papular type, associated with skeletal or neurological abnormalities. T
hree new cases of this recently delineated syndrome are presented. A common origin may account for the temporal and spatial relationship between the epidermal and the speckled lentiginous nevus.
The concept of melanocytic-epidermal twin spotting similar to the interpretation of vascular twin spotting could explain the pathogenesis of this entity.
HISTOLOGICAL TYPES CHARACTERIZATION General VARIANTS
Abnormal neuronal migration and gliomatosis cerebri in epidermal nevus syndrome.
Choi BH, Kudo M.
Acta Neuropathol (Berl) 1981;53(4):319-25 Abstract quote
A detailed neuropathologic examination of the brain of a child with the typical epidermal nevus syndrome revealed a primary disturbance of development of the brain.
The developmental disturbance consisted of an abnormal or incomplete migration of neurons to form the cerebral and cerebellar cortices. The normal architectonic pattern of the cortical layer formation of the cerebrum and cerebellum was also disturbed. In addition, there was an abnormality in the proliferative activity of astroglial cells resulting in gliomatosis cerebri.
It is suggested that the basic abnormality underlying various neurologic derangements in epidermal nevus syndrome is the result of a defect in specific developmental events, such as neuronal migration and cortical differentiation.
Epidermal nevus syndrome with hemimegalencephaly: a clinical report of a case with acanthosis nigricans-like nevi on the face and neck, hemimegalencephaly, and hemihypertrophy of the body.
Sakuta R, Aikawa H, Takashima S, Yoza A, Ryo S.
Department of Pediatrics, Numazu City Hospital, Shizuoka, Japan. A
Brain Dev 1989;11(3):191-4 Abstract quote
A 5-year-old boy with the epidermal nevus syndrome and hemimegalencephaly is reported.
He had pigmented nevi on the forehead and neck, and hemihypertrophy of the body from the birth. He developed intractable seizures, mental retardation, and right hemiparesis. His seizure pattern changed from early infantile epileptic encephalopathy to infantile spasms at 2 months of age. Electroencephalograms showed a suppression-burst pattern in the neonatal period, subsequently changing to hypsarrhythmia. Computerized tomography of the brain disclosed slight dilatation of the posterior horn of the lateral ventricle at the age of 2 months. Later, hemimegalencephaly with calcification on the left side of the brain was noted.
Histological examination of the pigmented nevus on the neck showed it to be an acanthosis nigricans-like lesion. Clinical differences between tuberous sclerosis and epidermal nevus syndrome with hemimegalencephaly are discussed.
Epidermal nevus syndrome with hemimegalencephaly: neuropathological study.
Sakuta R, Aikawa H, Takashima S, Ryo S.
Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan
Brain Dev 1991 Jul;13(4):260-5 Abstract quote
A neuropathologic examination of a 5-year-boy with epidermal nevus syndrome and hemimegalencephaly revealed 1) left hemimegalencephaly with an increased volume of the white matter, and 2) cerebral polymicrogyria with pachygyria, heterotopic neurons and prominent astrogliosis. Golgi staining revealed hypertrophic neurons with increased dendrites and spines.
The hemihypertrophy of the cerebral hemispheres seems to have contributed to an increased volume of the white matter with migration disorder, and may have been due to a disorder in the germinal cell proliferation stage.
Epidermal nevus syndrome: a neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy.
Pavone L, Curatolo P, Rizzo R, Micali G, Incorpora G, Garg BP, Dunn DW, Dobyns WB.
Pediatric Clinic, University of Catania, Italy.
Neurology 1991 Feb;41(2 ( Pt 1)):266-71 Abstract quote
The epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder that consists of epidermal nevi and congenital anomalies involving the brain and other systems.
From among over 60 patients with ENS presenting with neurologic manifestations, we identified 17 who had hemimegalencephaly based on pathologic or radiologic studies.
Associated brain and neurologic abnormalities included gyral malformations in 12 of 12, mental retardation in 13 of 14, seizures in 16 of 17 (including 9 with infantile spasms), and contralateral hemiparesis in 7 of 12. All had ipsilateral epidermal nevi of the head, and several had ipsilateral facial hemihypertrophy. We concluded that these abnormalities comprise a recognizable neurologic variant of ENS that we believe represents the full expression of primary brain involvement. Several patients also had evidence of acquired brain lesions such as infarcts, atrophy, porencephaly, and calcifications, which are best explained by prior ischemia or hemorrhage.
Given repeated observations of blood vessel anomalies in ENS patients, we hypothesize that underlying vascular dysplasia predisposes to these acquired lesions. The same cause may be invoked to explain the wide variety of neurologic symptoms reported in ENS patients without hemimegalencephaly. While the cause of ENS remains unknown, several observations suggest a somatic mutation.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Development of both cutaneous and visceral malignancies Treatment
Epidermal nevus syndrome: a review and case report.
Losee JE, Serletti JM, Pennino RP.
Division of Plastic Surgery, University of Rochester, NY 14642, USA.
Ann Plast Surg 1999 Aug;43(2):211-4 Abstract quote
The epidermal nevus syndrome is a disease complex of epidermal nevi and developmental abnormalities of different organ systems.
The authors present a case of congenital systematized epidermal nevus syndrome in a patient with skin lesions covering approximately 80% of the total body surface area. The patient underwent staged treatment of the epidermal nevi with a carbon dioxide laser utilizing two different techniques. The larger verrucous lesions were debulked initially, and the resulting defects and thinner lesions were treated using the Silk Touch modality. The lesions were dermaplaned sequentially until they were ablated completely. All wounds healed without complication, and in a 2-year follow-up the patient has experienced no recurrence in the treated areas.
Epidermal nevi can be treated safely, effectively, and without recurrence with carbon dioxide laser ablation.
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