Special article How many epidermal nevus syndromes exist? A clinicogenetic classification Rudolf Happle, MD Nijmegen, The Netherlands The term epidermal nevus syndrome is not suitable to describe an entity because there are different birth defects associated with epidermal nevi. A new classification is proposed to dis~ tinguish three well-defined syndromes, each recognizable by a different type of nevus. The sebaceous nevus syndrome and the Proteus syndrome are most likely due to autosomal lethal mutations and therefore always occur sporadically, whereas the CHILD syndrome can be transmitted from a mother to her daughter as an X-linked dominant, male-lethal trait. Moreover, the nevus comedonicus syndrome can be regarded as an entity closely related to this grbup of disorders. It may represent another autosomal lethal mutation that survives by mosaicism. In addition, several less well-defined phenotypes associated with epidermal nevi are reviewed. Some of them are regarded as entities in limbo. (J AM ACAD DERMATOL 1991;25:550-6.)

The term epidermal nevus syndrome l , 2 has led to much confusion. Many dermatologists erroneously believe that this name refers to a clinical entity.3-8 In fact, such an entity does not exist. Rather, several distinct birth defects have been lumped together under this designation. It is the purpose of this review to provide a new classification of epidermal nevus syndromes based on clinical, histopathologic, and genetic criteria. Apart from the well-defined entities, it seems useful to include, for heuristic purposes, some less well-defined syndromes characterized by epidermal nevi. For the sake of simplicity the term epidermal nevus will be used in a broad sense, including types that have adnexal differentiation. 2,7 WELL-DEFINED EPIDERMAL NEVUS SYNDROMES

The three syndromes that can be considered wellestablished entities are sebaceous nevus syndrome, Proteus syndrome, and CHILD syndrome (Table I). They are discussed in the fon~wing paragraphs. Sebaceous nevus syndrome This multisystem birth defect is also known by the terms linear sebaceous nevus syndrome9 and organoid nevus syndrome. to (The expression "linear seFrom the Department of Dermatology, University of Nijmegen. Reprint requests: R. Happle, MD, Department of Dermatology, University of Marburg, Deutschhausstr, 9, D-3550 Marburg, Germany.

16/1/27904

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Fig. 1.' Characteristic cutaneous lesions of sebaceous nevus syndrome;

baceous nevus" is redundant because all sebaceous nevi tend to be arranged in a linear pattern.) The phenotype was comprehensively described by

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How many epidermal nevus syndromes exist? 551

Table I. Well-defined epidermal nevus syndromes Sebaceous nevus syndrome

No. of entries in McKusick's catalog Type of nevus

Proteus syndrome

CHILD syndrome

163,200 and 165,630

176,920

308,050

Nevus sebaceus

CHILD nevus

Cutaneous pattern of distribution

Lines of Blaschko

Soft, flat, nonorganoid epidermal nevus Lines of Blaschko

~ventualspontaneous

No

No

Yes

Mental retardation, seizures, coloboma, lipodermoid of conjunctiva

Hypoplasia or aplasia of limbs; anomalies of brain, heart, or kidney

regression of nevus Major associated features

Heritability Underlying mutation

No Autosomal, lethal

Gigantism of limbs, focal skeletal hyperplasia, subcutaneous hamartomas No Autosomal, lethal

Type of mosaicism Sex ratio

Genomic 1:1

Genomic 1:1

Schimmelpenning11 in 1957. His patient had epileptic seizures, spastic hemiparesis and ataxia, deformities of the skull, coloboma of the eyelid, symblepharon, corneal opacities, and ipsilateral nevus sebaceus of the scalp and face. Schimmelpenning concluded that the symptoms this patient had "did not correspond to any of the well-known phakomatoses." Similar cases have subsequently been described under various synonyms such as linear nevus sebaceus with convulsions and mental retardation,12 linear sebaceous nevus syndrome,9,13, 14 organoid nevus syndrome,lO organoid nevus phakomatosis,15,16 Schimmelpenning-Feuerstein-Mims syndrome,15 J adassohn nevus phakomatosis,17, 18 epidermal nevus syndrome,1,3,19 and Solomon syndrome. 6 As a consequence of the confusing nomenclature, this nonmendelian trait has two entries in McKusick's catalog20 (see Table I). The sebaceous nevus that constitutes a hallmark of the syndrome (Fig. I) may be of any size. This term does not refer exclusively to a "relatively small" and "localized (usually less than 6 em)" lesion, as suggested by Solomon and Esterly. 2 On the contrary, this nevus may involve large parts ofthe body. When histopathologic examination fails to reveal hyperplasia of sebaceous glands, the syndrome cannot be identified with certainty. It should be borne in mind that before puberty organoid differentiation

Both linear (lines of Blaschko) and nonlinear, with sharp midline separation

Yes.

X-linked dominant, male-lethal Functional (lyonization) Almost exclusively women (42:2)

may be minimal or even absent in a sebaceous nevus of the scalp,21 and at any age in those parts of a sebaceous nevus that involve the trunk or the extremities. 2 The syndrome always occurs sporadically. This may be best explained by the action of a lethal mutation that survives by mosaicism. 22 The phenotype is not heritable because the underlying mutation, when present in a zygote, will lead to death of the embryo. Cells that carry the mutation can survive only in close proximity to normal cells.

Proteus syndrome This complex birth defect comprises partial gigantism of hands or feet, hemihypertrophy (including macrocephaly, subcutaneous hamartomas such as hemangioma, cystic lymphangioma, lipoma, and cerebriform hyperplasia of the plantar connective tissue), and a systematized epidermal nevus. 23 In contrast to the sebaceous nevus syndrome, this nevus is of the flat, velvety, papillomatous type (Fig. 2).24-29 In some reports this skin lesion has been inappropriately described as "linear sebaceous nevus, "30, 31 "pigmented nevi,,,23 or "pigmented and depigmented streaks."32 Any combination of these anomalies is possible. The phenotype was named after the Greek god Proteus because of the variability in the associated

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Fig. 3. Macrodactyly as a characteristic feature of Proteus syndrome.

Fig. 2. Epidermal nevus of flat, velvety, nonorganoid type as a feature of Proteus syndrome. (From Wiedemann HR, Burgio GR, Aldenhoff P, et al. Bur J Pediatr 1983;140:5-12; reproduced with permission.)

defects. 23 The most characteristic findings are asymmetric macrodactyly (Fig. 3) and cerebriform hyperplasia of the plantar connective tissue. The epidermal nevus is present in most patients,29 but its absence does not change the diagnosis. All cases are sporadic. The disease can also be best explained by the action of a lethal mutation that survives by mosaicism. 33 A typical example has been reported under the designation epidermal nevus syndrome. 34 Solomon et a1. 1 mentioned "enlarged limbs" or "localized gigantism" in some patients. These were observed after submission of their paper, and were photographically documented in a subsequent article. 2 They are suggestive of the Proteus syndrome, but they cannot be categorized with certainty.

CHILD syndrome The acronym CHILD was originally proposed for "congenitalhemidysplasia with ichthyosiform eryth-

roderma and limb defects,"35 but today the more appropriate interpretation "congenital hemidysplasia with ichthyosiform nevus and limb defects" should be used. 36 In contrast to the sebaceous nevus syndrome and Proteus syndrome, the phenotype is characterized by an inflammatory, ichthyosiform nevus that may involve large areas of the body without any linear pattern,35, 37, 38 although lesions that follow the lines of Blaschko may also be present (Fig. 4).4,39-41 Spontaneous partial regression of the nevus is not uncommon,35, 42-44 but periods of increase may also occur.40, 41, 45 Several authors have mistaken the CHILD nevus for ILYEN (inflammatory linear verrucous epidermal nevus).4,46 It should be noted that the CHILD nevus can be distinguished from ILYEN by its yellow, waxlike scales, mildness or even absence of itching, ptychotropism (affinity to body folds), a tendency to nonlinear arrangement, and histopathologic features of verruciform xanthoma. 36 The CHILD syndrome is a hereditary trait with an X-linked dominant mode oftransmission. 44 The disorder occurs almost exclusively in girls because the underlying gene has a lethal effect on male embryos. In contrast to genomic mosaicism as present in the sebaceous nevus syndrome and the Proteus syndrome, affected girls are composed of two populations of cells that are genetically identical but functionally different, because of the Lyon effect of X-inactivation. 35 Solomon et al. 1,2 have included this phenotype37 in the spectrum of "the epidermal

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How many epidermal nevus syndromes exist? 553

nevus syndrome," and this unjustified concept has been adopted by others. 3,4, 6, 40, 42, 47,48 A WELL-DEFINED RELATED DISORDER: NEVUS COMEDONICUS SYNDROME

Nevus comedonicus is, strictly speaking, not an epidermal lesion but an organoid nevus of epithelial origin. Nevus comedonicus syndrome49 can therefore be categorized as a disorder related to the group of epidermal nevus syndromes. This phenotype is extremely rare and includes skeletal defects,49-51 cerebral anomalies,52 and cataracts.52, 53 The association is certainly not fortuitous because a close topographic relationship between cutaneous and skeletal lesions has been reported (Fig. 5).50 The genetic basis of this disorder cannot be determined with certainty, but a lethal autosomal mutation that survives by mosaicism 33 is most likely. LESS WELL-DEFINED EPIDERMAL NEVUS SYNDROMES

From the following observations on various less well-defined syndromes, the emergence of other distinct entities should be expected in the future. For example, the reports of widespread verrucous epidermal nevi associated with angiodysp1asia, including aneurysms, display a remarkable consistency.5, 54-56 The nevus is of the nonepidermolytic type and has also been described as "ichthyosis hystrix,"55 It is not quite certain, however, that this is an entity distinct from sebaceous nevus syndrome because abnormal development of arteries has also been reported to be associated with the latter phenotype.57 I have seen a linear epidermal nevus of the soft, velvety, papillomatous type in a patient with KlippelTrenaunay syndrome, and a similar association has been reported by others.58, 59 Viljoen et al.60 described "darkly pigmented streaks" in four cases of Klippe1-Trenaunay syndrome, and most likely they refer to flat epidermal nevi because in another article they use the same vagueness in terminology to describe linear epidermalnevi.32 Itis unclear whether these observations represent oligosymptomatic forms of the Proteus syndrome or a distinct birth defect. In the latter case, the phenomenon of twin spotting may be considered to explain this association. 61 The event of mitotic recombination would constitute an etiologic link between the Klippel-Trenaunay syndrome and the epidermal nevus.

Fig. 4. Unilateral ichthyosiform nevus as a characteristic feature of CHILD syndrome. MISCELLANEOUS BIRTH DEFECTS ASSOCIATED WITH EPIDERMAL NEVI

Rustin et al.62 observed an extensive verrucous epidermal nevus of the nonorganoid, nonepidermolytic type in a patient with polyostotic fibrous dysplasia. A similar association has been described by Pierini et al.63 It is unclear whether these epidermal nevi should be considered a feature of classical McCune-Albright syndrome. Jancar64 observed a nevus syringocystadenomatosus papi11iferus associated with skeletal and neurologic defects. Several authors have described vitamin D-resistant rickets associated with a linear sebaceous nevus. 65 .68 These cases may belong to the broad spectrum of the sebaceous nevus syndrome, or they may constitute a distinct subtype.~ Ment et al. 70 described a linear pig-

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Fig. 5. Nevus comedonicus syndrome, a phenotype closely related to the group of epidermal nevus syndromes. A, Characteristic lesion on right arm. B, Aplasia of fifth digit of right hand. (From Schneider C. Hautarzt 1975;26:153-4; reproduced with permission.) mentary disorder in combination with a flat epidermal nevus of the nonepidermolytic type in an infant suffering from cleft palate, patent ductus arteriosus, arhinencephalia, and immune deficiency. Bafverstede! observed a widespread, hystrixlike epidermal nevus in a man with severe mental retardation and epilepsy. These cases cannot be assigned to a specific entity. It seems prudent, however, not to lump them as one single syndrome, nor to consider them "variants" of each other. CONCLUSION

When the present classification is considered, there remains no entity to be called "the epidermal nevus syndrome." The true number of different epidermal nevus syndromes is not known, but there are at least three distinct entities, the sebaceous nevus syndrome, the Proteus syndrome, and the CHILD syndrome. Furthermore, the nevus comedonicus syndrome can be regarded as a related disorder.

It may be interesting to apply the proposed classification to the twelve original cases reported by Solomon et a1.! Their cases land 7 are typical examples of the sebaceous nevus syndrome. Cases 8 and 10 cannot be classified, although they are reminiscent of the CHILD syndrome. Cases 5 and 11 probably do not represent any syndrome at all. A mild length difference of legs observed in case 11 may be fortuitous because the epidermolytic type of epidermal nevus is not known to be associated with other defects. The remaining six cases certainly do not constitute any syndrome because they represent isolated verrucous epidermal nevi of either the nonepidermolytic type (cases 3, 4, 6, and 9) or the epidermolytic type (cases 2 and 12). For example, trivial findings such as "bilateralfirst cervical ribs" (case 2) or "minimal lumbar lordosis" (case 6) are not sufficient to establish firmly an osteocutaneous syndrome. With regard to genetic counseling, Solomon and Esterly2 had to be vague: "It appears, then, that most

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cases of epidermal nevus syndrome occur sporadically, but enough data have been accumulated to arouse suspicion that autosomal dominant transmission may be present. For purposes of genetic counseling we inform patients with large epidermal nevi that genetic transmission is possible but that the data are inadequate at this time to draw conclusions." The present classification has the advantage of providing a rationale to draw specific conclusions. None of the syndromes herein discussed, with the exception of the CHILD syndrome, is transmitted to live born children (see Table I). All epidermal nevus syndromes are mosaic phenotypes, and therefore they may also occur without any cutaneous involvement. In these cases a definite diagnosis is not possible, with the exception of the Proteus syndrome, which can be recognized by other characteristic features. On the other hand, the various underlying mutations may manifest themselves exclusively in the form of an epidermal nevus. 72 The term nevus unius lateris73 -75 is hopelessly vague and should be avoided. Both unilateral and bilateral involvement of the body can be observed with any specific type of epidermal nevus, and this is not a significant factor in diagnosis. The present classification of epidermal nevus syndromes is a first approach that may be modified in the future. It is the main purpose of this review to draw attention to the remarkable clinical and genetic heterogeneity of these syndromes. An appropriate diagnosis is desirable both from a heuristic point of view and for the practical purpose of genetic counseling. REFERENCES 1. Solomon LM, Fretzin DF, Dewald RL. The epidermal nevus syndrome. Arch Dermatol 1968;97:273-85. 2. Solomon LM, Esterly NB. Epidermal and other congenital organoid nevi. Curr Probl Pediatr 1975;6:1-56. 3. Larregue M, Coseas G, Maselef P, et aI. Le syndrome du naevus epidermique de Solomon. Ann Dermatol Syph 1974;101:45-55. 4. Golitz LE, Weston WL. Inflammatory linear verrucous epidermal nevus. Association with epidermal nevus syndrome. Arch Dermatol 1979;115:1208-9. 5. Ratzenhofer E, Hohlbrugger H, Gebhart W, et aJ. Linearer epidermaler Naevus mit multiplen Missbildungen ("epidermal nevus syndrome" Solomon). Klin Padiatr 1981; 193: 117-9. 6. Raynaud F, Saurat JH. Le syndrome de Solomon (syndrome du naevus epidermique). Sa place en pediatrie generale. Ann Pediatr (Paris) 1982;29:46-52. 7. Atherton DJ, Rook A. Naevi and other developmental defects. In: Rook A, Wilkinson DS, Ebling FJG, et ai, eds. Textbook of dermatology. 4th ed. Oxford: Blackwell, 1986:167-227.

How many epidermal nevus syndromes exist? 555 8. Rogers M, McCrossin I, Commens C. Epidermal nevi and the epidermal nevus syndrome. A review of 131 cases. JAM ACAD DERMATOL 1989;20:476-88. 9. Lansky LL, Funderburk S, Cuppage FE, et al. Linear sebaceous nevus syndrome. A hamartoma variant. Am J Dis Child 1972;123:587-90. 10. Barth PG, Valk J, Kalsbeek GL, et al. Organoid nevus syndrome (linear nevus sebaceus of Jadassohn): clinical and radiological study of a case. Neuropadiatrie 1977;8: 418-28. 11. Schimmelpenning GW. Klinischer Beitrag zur Symptomatologie der Phakomatosen. Fortschr Rontgenstr 1957; 87:716-20. 12. Feuerstein Re, Mirns Le. Linear nevus sebaceus with convulsions and mental retardation. Am J Dis Child 1962;104:675-9. 13. Lovejoy FH, Boyle WE. Linear nevus sebaceous (sic) syndrome: report of two cases and a review of the literature. Pediatrics 1973;52:382-7. 14. Marks JG, Tomasovic 11. Linear nevus sebaceus syndrome. A case report. J AM ACAD DERMATOL 1980;2:31-2. 15. Hornstein LP, Knickenberg M. Zur Kenntnis des Sehimmelpenning-Feuerstein-Mims-Syndroms (organoide Naevus-Phakomatose). Arch Dermatol Forsch 1974;250:3350. 16. Kuokkanen K, Koivikko M, Alavaikko M. Organoid nevus phakomatosis. Acta Derm Venereal (Stockh) 1980;60: 534-7. 17. Vles ISH, DegraeuweP, DeCockP, etaJ. Neuroradiological findings in J adassohn nevus phakomatosis: a report of four cases. Eur J Pediatr 1985;144:290-4. 18. Zaremba 1. Jadassohn's naevus phakomatosis: 2. a study based on a review of thirty-seven cases. J Ment Defic Res 1978;22:103-23. 19. Eichler C, Flowers FP, Ross J. Epidermal nevus syndrome: case report and review of clinical manifestations. Pediatr DermatoI1989;6:316-20. 20. McKusick VA. Mendelian inheritance in man. Catalogs of autosomal dominant, autosomal recessive, and X-linked phenotypes. 9th ed. Baltimore: Johns Hopkins University, 1990. 21. Steigleder GK, Cortes AC. Verhalten der Talgdriisen im Talgdriisennaevus wahrend des Kindesalters. Arch Klin Exp Dermatol 1971;239:323-8. 22. Bapple R. Cutaneous manifestation of lethal genes. Hum Genet 1986;72:280. 23. Wiedemann HR, Burgio GR, AldenhoffP, et al. The Proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr 1983;140:5-12. 24. Burgio GR, Wiedemann HR. Further and new details on the Proteus syndrome. Eur J Pediatr 1984;143:71-3. 25. Hornstein L, Bove KE, Towbin RB. Linear nevi, hemihypertrophy, connective tissue hamartomas, and unusual neoplasms in children. J Pediatr 1987;110:404-8. 26. Malamitsi-Puchner A, Kitsiou S, Bartsocas CS. Brief clinical report: severe Proteus syndrome in an 18-month-old boy. Am J Med Genet 1987;27:119-25. 27. Bendick C. Proteus-Syndrom. Z Hautkr 1988;63:687-8. 28. Cohen MM Jr. Understanding Proteus syndrome, unmasking the elephant man, and stemming elephant fever. Neurofibromatosis 1988;1:260-80. 29. Hotamisligil GS. Ertogan F. The Proteus syndrome: association with nephrogenic diabetes insipidus. Clin Genet 1990;38:139-44. 30. Miicke J, Willgerodt H, Kunze! R, et aJ. Variability in the

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31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46.

Proteus syndrome: report of an affected child with progressive lipomatosis. Eur J Pediatr 1985;143:320-3. Clark RD,Donnai D, Rogers J, et al. Proteus syndrome: an expandeli phenotype. Am J Med Genet 1987;27:99-117. Yiljoen DL, Saxe N, Temple-Camp C. Cutaneous manifestations of the Proteus syndrome. Pediatr Dermatol 1988;5:14-21. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J AM: ACAD DERMATOL 1987;16:899-906. Attia MK, Abdel-Aziz AM. Epidermal naevus syndrome. Br JDermatoI1976;95:647-8. Happle R, Koch H, Lenz W. The CHILD syndrome. Congenital hemidysplasia with ichthyosiform erythroderma and limb defects. Eur J Pediatr 1980;134:27-33. Happle R. Ptychotropism as a cutaneous feature of the CHILD syndrome. J AM ACAD ])ilRMATOL 1990;23: 763-6. Rossman RE, Shapiro EM, Freeman RG. Unilateral ichthyosiform erythroderma. Arch DermatoI1963;88:567-71. Cullen SI, Harris DE, Carter CH, et al. Congenital unilateral ichthyosiform erythroderma. Arch Dermatol 1969; 99:724-9. Enjolras 0, Guerin D, Hewitt 1. Contribution ala connaissanee du syndrome du naevus epidermique de Solomon. Ann Dermatol VenereoI1979;106:673-80. Poiares BaptistaA, Cortesao JM. Naevus epidermique inflammatoire variable (N.E.V.I.L. atypique? entite nouvelle?) Ann Dermatol VenereoI1979;106:443-50. Zamora-Martinez E, Martin-Moreno L, Barat-Cascante A, et al. Another CHILD syndrome with xanthomatous pattern. Dermatologica 1990;180:263-6. Lambert D, Michiels Y,Nivelon A, et al. Naevus epidermique unilateral complexe a evolution regressive. Bull Soc Fr Dermatol Syph 1974;81 :243-4. Lipsitz PJ, Suser F, Weinberg S, et al. Congenital unilateral ichthyosis in a newborn. Am J Dis Child 1979;133: 76-8. Happle R, Karli6 D, Steijlen PM. CHILD-Syndrom bei Mutter und Tochter. Hautarzt 1990;41:105-8. Pilz I, Swoboda W. Chondrodysplasia punctata. Padiatr Prax 1979;22:135-41. Haustein. UF, Siiss E. Inflammatorischer linearer vermkoser epidermaler Navus (ILVEN). Dermatol Monatsschr 1978;164:120·9~

47. Lambert D, Dalac S, Aiison M, et aL Epidermal nevus associated with ganglioneuroblastoma. In: Wilkinson DS, Mascar6 JM, Orfanos CE, eds. Clinical dermatology. The CMD case collection. Stuttgart: Schattauer, 1987;48-9. 48. Parsch EM, Georgii A, Konz B. Solomon-Syndrom. In: Braun-Falco 0, Ring J, eds. Fortschritte der praktischen Dermatologie und Venerologie. Zwiilfter Band. Berlin: Springer, 1990:538-9. 49. Engber PB. The nevus comedonicus syndrome: a case report with emphasis on associated internal manifestations. Int J DermatoI1978;17:745-9. 50. Schneider C. Ein Beitrag zur Klinik des Naevus comedonicus. Hautarzt 1975;26:153-4. 51. Cripps DJ, Bertram JR. Nevus comedonicus bilateralis et verruciformis. J Cutan pathoI1976;3:273-81. 52. Popov L, Boianov L. Neopisan woden kozhno-ochen sindrom (syndroma cataracto-comedonicum congenitale) [In Bulgarian, with an English summary]. SuYr Med (Sofia) 1962;13:49-50. 53. Whyte HJ. Unilateral comedo nevus and cataract. Arch Dermato1 1968;97:533-5.

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54. McAuley DL, Isenberg DA, Gooddy W. Neurological involvement in the epidermal naevus syndrome. J Neural Neurosurg Psychiatr 1978;41:466-9. 55. Burch JV, Leveille AS, Morse PH. Ichthyosis hystrix (epidermal nevus syndrome) and Coats' disease. Am J Ophthalmol 1980;89:25-30. 56. Marsch WC, Taube KJ, Kasemann B. Ein Solitarfall von Ichthyosis hystrix gravior unilateralis. Klinische und morphologische Befunde. Z Hautkr 1981;56:1073-80. 57. Marden PM, Venters HD. A new neurocutaneous syndrome. Am J Dis Child 1966;112:79-81. 58. Palatsi R. A case of the Klippel-Trenaunay-Parkes Weber syndrome. Acta Derm Venereol (Stockh) 1975;55:233-6. 59. Wilder J, StarinkTM. Acanthosis nigricans-like epidermal naevus and Klippel-Trenaunay syndrome. Br J Dermatol 1990;123:539. 60. Viljoen D, Saxe N, Pearn J, et al. The cutaneous manifestations of the Klippel-Trenaunay-Weber syndrome. Clin Exp DermatoI1987;12:12-7. 61. Bapple R; Koopman R, Mier PD. Hypothesis: vascular twin naevi and somatic recombination in man. Lancet 1990;335:376-8. 62. Rustin MHA, Bunker CB, Gilkes JJH, et al. Polyostotic fibrous dysplasia associated with extensive linear epidermal naevi. Clin Exp Dermatol1989;14:371-5. 63. Pierini AM, Ortonne JP, FloretD. Signes dermatologiques du syndrome de McCune-Albright. A propos d'un cas. Ann Dermatol VenereoI1981;108:969-76. 64. Jancar 1. Naevus syringocystadenomatosus papilliferus with skull and brain lesions, hemiparesis, epilepsy and mental retardation. Br J Dermatol 1970;82:402-5. 65. Sugarman GI, Reed WB. Two unusual neurocutaneous disorders with facial cutaneous signs. Arch Neurol 1969; 21:242-7. 66. Moorjani R, Shaw DO. Feuerstein and Mims syndrome with resistant rickets. Pediatr Radiol 1976;5:120-2. 67. Aschinberg LC, Solomon LM, Zeis PM, et al. Vitamin Dresistant rickets associated with epidermal nevus syndrome: demonstration of a substance in the dermal lesions. J Pediatr 1977;91:56-60. 68. Carey DE, Drezner MK, Hamdan JA, et al. Hypophosphatemic rickets/osteomalacia in linear sebaceous nevus syndrome: a variant of tumor-induced osteomalacia. J Pediatr 1986;109:994-1000. 69. Fritz M, Gassenmaier A, Gassenmaier G, et al. Linearer epidermaler Naevus, Hamangiomatose der Rohrenknochen und hypophosphatamische Rachitis. Eine Variante des epidermalen Naevussyndroms? Aktuel Dermatol1988; 14:58-60. 70. Ment L, Alper J, Sirota RL, et al. Infant with abnormal pigmentation, malformations, and immunedeficiency. Arch DermatoI1978;114:1043-4. 71. Bafverstedt B. Fall von genereller, naevusartiger Hyperkeratose, Imbecillitiit, Epilepsie. Acta Derm Venereol (Stockh) 1941;22:207-12. 72. Lentz CL, Altman J, Mopper C. Nevus sebaceus of Jadassohn. Report of a case with multiple and extensive lesions and an unusual linear distribution. Arch Dermatol 1968; 97:294-6. 73. Von Baerensprung FWF. Naevus unius lateris. Ann Charite-Krankenhaus (Berl) 1863;11:91-5. 74. Pack GT, Sunderland DA. Naevus unius lateris. Arch Surg 1941;43:341-75. 75. Muller JT, Pickett AB, Frederick FD. Facial hemihypertrophy associated with nevus unius 1ateris syndrome. Oral Surg Oral Med Oral PathoI1980;50:226-8.