Ebook Vitiligo and other hypomelanoses of hair and skin: Part 1

(BQ) Part 1 book Vitiligo and other hypomelanoses of hair and skin presents the following contents: Skin color and the melanin pigmentary system, approach to the problem of leukoderma, hypomelanotic disorders.

Vitiligo and Other Hypomelanoses of H air and Skin TOPICS IN DERMA TOLOGY Series Editors: John A Parrish and Thomas B Fitzpatrick Harvard Medical School, Boston, Massachusetts VITILIGO AND OTHER HYPOMELANOSES OF HAIR AND SKIN Jean-Paul Ortonne, David B Mosher, and Thomas B Fitzpatrick Vitiligo and Other Hypomelanoses of Hair and Skin Jean-Paul Ortonne, M.D H6pital Pasteur Centre Hospitalier Universitaire Nice, France David B Mosher, M.D and Thomas B Fitzpatrick, M.D Massachusetts General Hospital Harvard Medical School Boston, Massachusetts PLENUM MEDICAL BOOK COMPANY New York and London Library of Congress Cataloging in Publication Data Ortonne, Jean-Paul, 1943Vitiligo and other hypo melanoses of hair and skin (Topics in dermatology) Includes bilbiographical references and index Vitiligo Pigmentation disorders I Mosher, David B II Fitzpatrick, Thomas B III Title IV Series [DNLM: Pigmentation disorders Skin manifestations WR 265 078v] RL790.077 1982 616.5 82-16490 e-ISBN-13: 978-1-4615-9272-3 ISBN-13: 978-1-4615-9274-7 DOl: 10.1 007/978-1-4615-9272-3 © 1983 Plenum Publishing Corporation Softcover reprint of the hardcover 1st edition 1983 233 Spring Street, New York, N.Y 10013 Plenum Medical Book Company is an imprint of Plenum Publishing Corporation All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Acknowledgments The authors wish to acknowledge the assistance of the many colleagues who have inspired and assisted them in this endeavor Particularly appreciated is the editorial review of Dr John A Parrish and the assistance of Dr Madhu A Pathak particularly in the areas of chemical leukoderma and vitiligo Diane Patry assisted with typing and copy preparation We are particularly indebted to Pat K Novak for her tireless diligence as copy editor v Preface Leukoderma is a generic term for any pigmentary dilution, be it congenital or acquired, circumscribed or generalized, devoid of or partially lacking in pigmentation In the approach to the diagnosis of leukoderma, we have generally first considered the age of onset, whether leukoderma was congenital or acquired, the extent and pattern of involvement, and the degree of pigmentary dilution The organization of this monograph reflects this approach For example, we have separated the section devoted to various disease entities into diffuse and circumscribed leukoderma and the latter into various etiologies such as genetic, metabolic, infectious, and endocrinologic One of several justifications for this monograph is to present an approach to the diagnosis of leukoderma, as detailed in Part II In formulating a guide for the physician, we have found some limitations to our previous approach; we therefore offer the following new classification based upon a clinical-pathologic correlation This could provide the means to describe both the clinical and pathologic findings in one term I Melanocytopenic leukoderma (reduction or absence of melanocytes) A Vitiligo B Piebaldism C Chemical leukoderma D Waardenburg's syndrome II Melanopenic leukoderma (reduction or absence of melanin) A Albinism B White macule of tuberous sclerosis C Nevus depigmentosis In the melanocytopenic leukodermas, melanocytes are absent and the macules are usually pure white However, in the melanopenic leukodermas, melanocytes are present, but there is a reduction of melanin, due to a defect in melanosome formation, melanization of melanosomes, melanosome transfer, or other process, so that mild to very marked pigmentary dilution is apparent Differential diagnosis of a melanocytopenic leukoderma that is congenital and circumscribed would, for example, have to include piebaldism, whereas if it were acquired and circumscribed, vitiligo and chemical leukoderma would vii viii PREFACE have to be considered Per contra, a melanopenic leukoderma that is acquired and circumscribed would include tinea versicolor, postinfiammatory hypomelanosis, leprosy, sarcoidosis, and idiopathic guttatehypomelanosis Melanopenic leukoderma that is congenital and circumscribed would include the white macules in tuberous sclerosis and nevus depigmentosis Most of the diffuse hypomelanoses are congenital melanopenic disordersthese include albinism and phenylketonuria Diffuse hypomelanoses that are exceptions include vitiligo universalis, which is an acquired melanocytopenia While this monograph itself does not embrace the newer terms "melanopenic" and "melanocytopenic," the tables, descriptive paragraphs, clinical photographs, and photomicrographs provide corresponding bases for the new terms which designate clinical-pathologic findings Jean-Paul Ortonne David B Mosher Thomas B Fitzpatrick Contents PART I SKIN COLOR AND THE MELANIN PIGMENTARY SYSTEM Melanins Epidermal Dendritic Cells Origin of Melanocytes Biologic Basis of Melanin Pigmentation Race, Light, Age, and Melanocytes Factors Controlling Pigmentation References 11 20 22 28 PART II APPROACH TO THE PROBLEM OF LEUKODERMA 37 History Physical Examination Histology and Electron Microscopy Pathogenesis Reference 40 41 51 54 56 PART III HYPOMELANOTIC DISORDERS 57 Chapter Genetic and Congenital Disorders 59 Section Disorders with Features of Oculocutaneous Albinism 59 Introduction Tyrosinase-Negative Oculocutaneous Albinism Tyrosinase-Positive Oculocutaneous Albinism Yellow-Mutant Oculocutaneous Albinism Hermansky-Pudlak Syndrome Chediak-Higashi Syndrome Albinism and Immunodeficiency Cross-McKusick-Breen Syndrome Oculocutaneous Albinoidism Ocular Albinism 59 65 69 74 75 79 87 88 89 89 ix x CONTENTS Abnormalities of the Optic Pathway in Albinism Other Defects in Albinos Differential Diagnosis Treatment of Albinism References 92 93 93 93 95 Section Disorders with Relative Generalized Decreased Pigmentation 102 Copper Deficiency Histidinemia Phenylketonuria Disorders of Methionine Metabolism Tietz Syndrome References 102 107 109 119 123 123 Section Disorders with Circumscribed Hypomelanosis 129 Vitiligo References Piebaldism References Waardenburg Syndrome References Piebaldism with Deafness (Woolf Syndrome) References Ziprkowski-Margolis Syndrome References Tuberous Sclerosis References Nevus Depigmentosus References Incontinentia Pigmenti Achromians References Incontinentia Pigmenti References Ataxia-Telangiectasia References Xeroderma Pigmentosum References Neurofibromatosis References Dyschromatosis Symmetrica; Dyschromatosis Universalis Hereditaria References Hypopigmented Markings in Dark-Skinned People: Pigmentary Demarcation Lines References 129 286 310 334 337 364 369 372 373 374 375 396 398 410 411 426 427 432 433 435 435 438 438 440 440 444 444 451 446 CHAPTER Subgroups Location Group A Arms B Legs (mid perineum straight to inner popliteal fossa) C Sternum D Back (downward on either side of midline) E Chest (linear from nipples toward midline) Mid inner upper arm to upper axilla and downward and toward the midline across pectorales muscles; may extend to flexor elbow and even to radial aspect of waist II Similar to I but passing horizontally from upper axilla toward midline III Similar to I and II, but pectoral portion dips inferiorly, then moves again in superior direction to the midline to join line from other side IV Terminus a vaguely defined white wedge pointed toward upper axillary border I Upper sternum medial to linea sternales to stomach; symmetrical II Upper sternum, then lines diverge inferiolaterally between mammary and inframammary regions I Clinical Findings Incidence Pigmentary demarcation lines are common, particularly in dark-skinned peoples A mediosternal depigmentation line has been reported in nearly 40% of 112 investigated blacks [3] In a study of 100 blacks [5], a mediosternal TABLE 110 Hypopigmented Markings in a Study of 100 Black Patientsa Number of patients by age and sex Number (and %) with mediosternal line Number (and %) with bilateral hypopigmented chest macules 100 Patients aged mo to 72 yr 26 Patients aged mo to 13 yr 74 patients aged 13 yr to 72 yr 38 (38%) 16 (16%) 18 (69%) 12 (46%) 20 (27%) (5%) 52 Males 48 Females 22 (42%) 16 (33%) 11 (10%) a (21%) From: Selmanowitz JV, Krivo JM: Hypopigmented markings in Negroes Int J DermatoI12:229-235, 1973 Copyright, 1973, J B Lippincott Co Used with permission depigmentation line was present in 38% and bilateral hypopigmented chest macules in 16% (Table 110) Sex Both males and females may be affected A mediosternal hypopigmentation line has been found in 42% of 102 male Negroes and 35% of 110 females [3,5] Bilateral hypopigmented chest macules were found in 21% of 52 black males and 10% of 48 black females [5] (Table 110) Race The hypopigmented markings have been obser'led only in dark-skinned people, principally Negroes, Japanese, and Spanish-Americans They also exist in Caucasoids but, because the contrast is faint, the pigmentary demarcation lines are less apparent Age The time of onset is unknown; in fact, in most of the cases these markings were not noted by the patient initially The incidence between six months and 13 years is greater than that between 13 and 72 years of age for both mediosternal lines and bilateral hypopigmented chest macules [5] Thus, there seems to be a progressive disappearance of these hypopigmented markings during growth and development of the individual The observation that in a given family these features are less apparent in parents than in their children reinforces this observation Heredity The inheritance pattern of hypopigmented macules of the anterior chest in five members of the same family strongly suggests autosomal dominant 447 GENETIC AND CONGENITAL DISORDERS 448 CHAPTER inheritance [4] Mediosternal depigmentation lines have been seen in a mother, her two children, and also her two sisters [3] However, because of the high incidence of such hypopigmented markings, coincidental occurrence in several individuals of the same family has to be considered Clinical Description Chest Hypopigmented Macules The principal lesion is a small hypopigmented but not totally amelanotic macule, about cm in size The margins of the lesions are ill defined The epidermis is otherwise normal Hair growth, sweating, and sensation are not disturbed In anyone patient there may be from several to 10 macules that may vary in size and shape These hypopigmented macules are always bilateral and usually symmetrical, but there is sometimes an asymmetrical distribution of lesions (Fig 180) Mediosternal Hypopigmentation Lines and Chest Hypopigmented Markings Chest-wall markings have been variously characterized as "broad and slightly curved ribbon-like markings with irregular margins and blunt ends," "narrower markings with tapered ends, somewhat leaf-shaped," and "longer streaklike FIGURE 180 Bilateral hypopigmented macules (arrows) and mediosternal line (broad arrow) Right: Periareolar hypopigmented macules The two macules indicated by arrows have leaf-shaped configurations The cause of the mediosternal line (broad arrow) is described in the text (From: Selmanowitz VJ Krivo JM: Hypopigmented markings in Negroes lnt JDermato112:229-235 1973 Copyright 1973 J B Lippincott Co Used with permission.) hypopigmentation." Lesions are usually located in the preareolar areas but have also been observed just below the mid portion of the clavicles, midway between the clavicles and nipples, and sometimes in a linear fashion from the nipples toward the midline The latter were described as Group E pigmentary demarcation lines by Selmanowitz and Krivo [7] Mediosternal hypopigmentation lines are located on the midline of the sternum and may extend longitudinally onto the abdominal skin (Figs 180, 181) In some patients, the hypopigmented band may involve the suprasternal area with a slight curvature of the band to one side Sometimes also the hypopigmentation line is not strictly located to the midline but arches away, sometimes taking a second change in direction Selmanovitz and Krivo [7] identified this latter as consistent with the pigmentary demarcation lines of Group C (Fig 182) described by Miura [6] Both types of mediosternal lines and chest macules can occur in the same individual FIGURE 181 Arrows indicate the hypo pigmented streaks The mediosternal line extends into the abdominal midline skin (broad arrows) (From: Selmanowitz VJ, Krivo JM: Hypopigmented markings in Negroes lnt J Dermato112:229-235, 1973 Copyright, 1973, J B Lippincott Co Used with permission.) 449 GENETIC AND CONGENITAL DISORDERS 450 CHAPTER Other pigmentary demarcation lines have been described Anterobrachial demarcations (Group A of Miura) have been described among blacks [5,8,9] and Japanese [6] (Fig 182) They may extend in a transpectoral direction It is not clear from the literature whether these pigmentary demarcation lines can appear as a hypopigmented streak, but a picture reported by Selmanowitz and Krivo [7] seems to show an area of hypopigmentation related to Group A pigmentary demarcation lines Group B (ventral axial lines of the inner thigh) [7] and Group E (posteromedian demarcation lines) [7] have also not been related to hypopigmentation in the literature These hypopigmented markings are not associated with other conditions and the individuals who bear them are usually in good health There are no other associated dermatologic findings Pigmentary demarcation lines is a relatively stable condition; the markings not seem to extend and, in some instances, they may progressively disappear with age [5] No histologic or electron microscopic studies of these hypopigmented markings are available FIGURE 182 The arrow points to a pronounced typical brachial demarcation line of pigmentation (Group A) A prominent line is also seen on the other arm The ends of the "V" on the chest abut a Type II mediosternal line (Group C) which arches from xiphisternal midline and returns to midline superiorly (From: Selmanowitz VJ Krivo JM: Pigmentary demarcation lines Br J Derrnatol 93:371-377 1975 Copyright 1975 Blackwell Scientific Publications Used with permission.) Diagnosis In some individuals the markings are so clear as to cause little doubt of their presence to an aware physician However, sometimes even in dark-skinned individuals they are very faint and can easily be overlooked In the latter case, Wood's light examination may be useful As pointed out by Selmanowitz and Krivo [5], the mediosternalline is not likely to be confused with anything else In a patient with hypopigmented chest macules, relevant history and the absence of other cutaneous lesions help to exclude postinflammatory hypopigmentation The presence of normal sensation on the hypopigmented macules excludes Hansen disease Tuberous sclerosis also may be present with a similar ash leaf-shaped macule, but in tuberous sclerosis the depigmentation is usually not an isolated finding and the depigmented patches are more numerous, widely distributed, and not bilaterally symmetrical Significance It is most probable that pigmentary demarcation lines are a dominantly inherited trait [1,4,5] and represents, as suggested by Selmanowitz and Krivo [7], a duality in the population of melanocytes These demarcation lines cause very slight cosmetic disfigurement and require no treatment REFERENCES Ito K: The peculiar demarcation of pigmentation along the so-called Voigt's line among the Japanese Dermatologia Internatl 44:45-47,1965 Matzumoto S: Ober eine eigentumliche Pigmentverteilung in den Voigtshen Linien (Beitrag zur Kenntnis der Voigtschen Grenzen) Arch Dermatol Syphilol (Berlin) 118:157-164, 1913 Kisch B, Nasuhoglu A: A mediosternal depigmentation line in Negroes Exp Med Surg 11:265-267, 1953 Weary PE, Behlen CH: Unusual familial hypopigmentary anomaly Arch Dermatol 92:54-55, 1965 Selmanowitz VI Krivo JM: Hypopigmented markings in Negroes Int J Dermatol12:229-235, 1973 Miura 0: On the demarcation lines of pigmentation observed among the Japanese, on inner sides of their extremities and on anterior and posterior sides of their medial regions Tohoku J Exp Med 54:135-140, 1951 Selmanowitz VI Krivo JM: Pigmentary demarcation lines-comparison of Negroes with Japanese Br J Dermotol 93:371-377, 1975 Fletcher PH: A peculiarity of pigmentation of the upper arm of Negroes Science 88:570-571, 1938 Vollum DI: Skin markings in Negro children from the West Indies Br J Dermotol 86:260-263, 1972 451 GENETIC AND CONGENITAL DISORDERS 452 OTHER MISCELLANEOUS SYNDROMES CHAPTER Darier-White Disease Darier-White disease is an uncommon autosomal dominant disorder of keratinization characterized by small hyperkeratotic papules usually located on the face, extremities, chest, and back Palms and soles, nails, and mucous membranes may be involved Spontaneous mutation is responsible for many cases Electron microscopic studies show a structural defect in the tonofilament-desmosome complex There are only a few scattered reports of leukoderma in Darier-White disease [1] Goodall and Richmond [2], in 1965, reported a 24-year-old woman with many macules of leukoderma on the upper extremities and trunk; it is possible that these represented postinflammatory changes Cornelison et al [3], in 1970, described guttate leukoderma associated with Darier-White disease Based on the presence of these widespread white macules among three of 15 patients with keratosis follicularis, Cornelison et al [3] concluded that guttate leukoderma with keratosis follicularis is more common than the scant attention afforded it in the literature would indicate These patients, two males and one female, respectively aged 21, 49, and 32, had had depigmented lesions since childhood None had a positive family history for the disease In all three patients, the white macules were numerous, to mm in diameter, asymptomatic, and randomly distributed around as well as between the hair follicles on the trunk and extremities None of the white macules occurred on the face According to the patients, no other lesions preceded the appearance of the white macules Dystrophic nail changes and characteristic keratotic papules in the typical distribution were also noted Histologic examination of white macules of two patients revealed decreased to absent epidermal melanin However, the typical histologic features of the disease, namely dyskeratosis, corps ronds or grains, were absent in these sites Cattano [4] reported a postinflammatory leukoderma in keratosis follicularis Histologic studies showed epidermal thinning, atrophy, and flattening of rete ridges Dopa-silver nitrate stain revealed a virtual absence of melanocytes Many hyperpigmented hyperkeratotic papules were present in this patient Autosomal Recessive Deafness Associated with Vitiligo (Rozycki Syndrome) Rozycki et al [5] described a syndrome of congenital deafness with profound sensorineural hearing loss, muscle wasting, short stature, hyperreflexia, achalasia, and vitiligo in two children of parents who were also first cousins In both, depigmented patches are described on their necks and trunks Both 453 GENETIC AND CONGENITAL DISORDERS FIGURE 183 a: Small hypomelanotic macules scattered over the lateral neck (Courtesy of D L RozyckL) b, c: Small hypomelanotic macules scattered over the lateral neck (Courtesy of D L RozyckL) 454 CHAPTER c FIGURE 183 (Continued) Muscle wasting involving the hands (a) and feet (b) of affected individuals (From: Rozycki DL et al: Autosomal recessive deafness associated with short stature vitiligo muscle wasting and achalasia Arch Otolaryngol 93:194-197 1971 Copyright 1971 American Medical Association Used with permission.) FIGURE 184 455 GENETIC AND CONGENITAL DISORDERS t • ~I n ot M - IIIItJ 't • "'''' -''11 "t OIfO "'l I~ ' o T t I-Ill DIAD ( MIIl o-t S4!1 ~ !tt ~~ ""-' ~tC)wN 00 ,""' FIGURE 185 Pedigree of the affected family (From: Rozycki DL et al: Autosomal recessive deafness associated with short stature vitiligo muscle wasting and achalasia Arch Otolaryngol 93:194-197 1971 Copyright 1971 American Medical Association Used with permission.) FIGURE 186 Barium swallow demonstrating dilatation of esophagus compatible with achalasia (From: Rozycki DL et al: Autosomal recessive deafness associated with short stature vitiligo muscle wasting and achalasia Arch Otolaryngol 93:194-197 1971 Copyright 1971 American Medical A~~nr.i"tinn Used with nermission.l 456 CHAPTER also had abnormal EEGs, slightly elevated beta and gamma globulins, decreased alpha globulins, and abnormal cephalin flocculation and thymol turbidity tests (Figs 183, 184, 185, 186) Focal Dermal Hypoplasia Syndrome Focal dermal hypoplasia is a rare congenital meso ectodermal syndrome which includes small stature, mental deficiency, and skeletal, ocular, oral and dental, and soft tissue defects The focal dermal hypoplasia syndrome predominantly occurs in females but may also involve males Hypopigmentation of the skin and hair may be one of the cutaneous features of this rare disorder In several patients, hyper- or hypopigmented areas of the skin have been observed to be linear or reticular [6] A nine-year-old black girl showed multiple areas of hypopigmentation, hyperpigmentation, and anetoderma distributed over the face, buttocks, legs, and thighs [7] (Figs 187, 188) Poliosis has also been reported in focal dermal hypoplasia [8] Additional cutaneous features include atrophy and linear hypermelanosis Abnormalities of dentition include hypodontia, oligodontia, and microdontia, dysp,lastic fragile enamel, delayed tooth eruption, and malocclusion Accompanying features of this syndrome include, characteristically, groups of linear yellow-red nodules and papillomas of mucosal surfaces, particularly the lips, but also of other periorificial skin-anus, eyes and genital region Localized fat deposits are seen in addition to small, thin, and dystrophic nails, and sparse, brittle hair accompanying patchy alopecia Muscular skeletal abnormalities include small stature and slender habitus with triangular facies marked by prominent ears, small rounded skull, and pointed chin Arms and legs may be asymmetrical Absence of a digit, syndactyly and polydactyly are common Ocular defects may include, most commonly, strabismus or coloboma and infrequently keratoconus Diagnosis of focal dermal hyperplasia is usually readily apparent in a Caucasian female with multiple characteristic findings A few cases in males have been reported, however, When the clinical expression, which may be highly variable, renders the diagnosis difficult, biopsy may be helpful Histopathologic studies show focally marked reduction in dermal thickness so that the epidermis is seated almost directly on subcutaneous fat The papillomas show only marked acanthosis and a vascular connective tissue Radiologic studies of long bones may also be useful-osteopathia striata or radioopaque metaphyseal stripes are found in many such cases of focal dermal hypoplasia Histopathologic studies, including split dopa and electron microscopy of the melanocytes in the abnormally melanized cutaneous areas, are not yet available Hypopigmentation with Punctate Keratosis of the Palms and Soles An 18-year-old man has been described with hypopigmented keratotic papules and irregular macules with varied degrees of hypopigmentation [9] 457 GENETIC AND CONGENITAL DISORDERS FIGURE 187 Multiple areas of anetoderma and hypopigmentation of buttocks, legs, and thighs at birth (From: Gottlieb SK et al: Focal dermal hypoplasia Arch Dermatol 108:551-553, 1973 Copyright, 1973, American Medical Association Used with permission.) 458 CHAPTER FIGURE 188 Multiple areas of anetoderma, hypopigmentation of posterior thighs and knees at age nine (From: Gottlieb SK et al: Focal dermal hypoplasia Arch Dermatol108:551-553, 1973 Copyright, 1973, American Medical Association Used with permission.) The macules varied from to 16 mm in diameter and from brown to light tan in color None of the macules depigmented totally The macules, which had sharply demarcated borders, were scattered over most of the body, but were sparse or absent on the acral portions of the body, including the head, neck, nipples, elbows, knees, genitalia, hands, and feet (Fig 189) Fontana-Masson silver stain showed melanin granules in the hypopigmented epidermis with occasional small collections of melanophages in the upper dermis Hair, mucous membranes, and irides were normally pigmented In addition, flat-topped hypopigmented keratotic papules were present on the palms, soles, and dorsolateral fingers and toes This patient also had a G6PD deficiency Other members of the family (maternal grandfather, mother, and three brothers) all also had the same dermatologic features The authors suggested an autosomal dominant pattern of inheritance 459 GENETIC AND CONGENITAL DISORDERS FIGURE 189 Sharply demarcated irregular hypomelanotic macules that were scattered all over the body in a patient with punctate keratosis of the palms and soles (From: Cole MLA: Hypopigmentation with punctate keratosis of the palms and soles Arch Dermatol112:998-1000 1976 Copyright 1976 American Medical Association Used with permission.) 460 CHAPTER Hypomelanoses in Possible Ectodermal Dysplasia Syndromes Freire-Maia et al [10] reported a seven-year-old girl with trichodysplasia, hypohydrosis, normal teeth, onychogryposis, psychomotor and growth retardation, dry and warm skin with follicular hyperkeratosis, bilateral nuclear cataracts, a peculiar facies (frontal bossing, depressed bridge of the nose), partial alopecia of the scalp, absence of eyebrows and body hair, and scarce eyelashes This girl had hyperpigmented macules on her feet, knees, arms, neck, and forehead and large hypopigmented macules on the anterolateral front forearm It was suggested that she had a genetic condition which may be a new form of ectodermal dysplasia But since the history of the onset and stability of these features is unknown, the depigmentation may in fact have been nevus depigmentosus Berlin [11] also described a congenital familial anomaly which he suggested may represent a special, unusual, incomplete and mixed type of ectodermal dysplasia The disorder, observed in two sons and two daughters of healthy parents, was characterized by a widely generalized leukomelanoderma especially involving the extremities and sparing only the scalp The mottled dyschromia exhibited the appearance of a leopard skin There were multiple abnormalities which included the following: stunted growth, thinness ofthe body, especially the legs (bird legs); mental retardation; and sexual underdevelopment in the males (hypospadia, small penis and scrotum, atrophy of the testes, absence of secondary sex signs) The appearance of the face was striking (sparse eyebrows, saddle-shaped nose, thick lips, wrinkling around the eyes and mouth) The eruption of the deciduous and permanent teeth was delayed and the pilosebaceous apparatus was underdeveloped In addition to the pigmentary abnormalities, the skin was thin, fine, and dry; there were also anetopoikilodermatous lesions, atrophic scars, and palmoplantar hyperkeratosis REFERENCES Cohen-Hadria M: Maladie de Darier (premier cas publie en Afrique du Nord); debut tras precoce; lesions zoniformes; leukodermie residuelle Bull Soc Fr Dermotol Syphiligr 46:1478-1481, 1939 Goodall JWO, Richmond QMS: A case of Darier's disease Br J Clin Proct 19:475-476, 1965 Cornelison RL et al: Guttate leukoderma in Darier's disease Arch Dermotol102:447-450, 1970 Cattano AN: An unusual case of keratosis follicularis Arch Dermotol 98:168-174, 1968 Rozycki DL et al: Autosomal recessive deafness Arch Otoloryngol 93:194-197, 1971 Goltz RW et al: Focal dermal hypoplasia syndrome Arch Dermotol101:1-11, 1970 Gottlieb SK et al: Focal dermal hypoplasia Arch Dermotol108:551-553, 1973 Marchionini A, Besser F: Ober Poikilodermia atrophicans vascularis Uacobi) Arch Dermotol Syphilol (Berlin) 165:431-442, 1932 Cole LA: Hypopigmentation with punctate keratosis of the palms and soles Arch Dermotol 112:998-1000, 1976 10 Freire-Maia N et al: A syndrome of hypohidrotic ectodermal dysplasia with normal teeth, peculiar facies, pigmentary disturbances, psychomotor and growth retardation, bilateral nuclear cataract and other signs J Med Genet 12:308-310, 1975 11 Berlin C: Congenital generalized melanoleukoderma associated with hypodontia, hypotrichosis, stunted growth, and mental retardation occurring in two sisters Dermotologico 123:227-243, 1961 ... RL790.077 19 82 616 .5 82 -16 490 e-ISBN -13 : 978 -1- 4 615 -9272-3 ISBN -13 : 978 -1- 4 615 -9274-7 DOl: 10 .1 007/978 -1- 4 615 -9272-3 © 19 83 Plenum Publishing Corporation Softcover reprint of the hardcover 1st edition... Massachusetts VITILIGO AND OTHER HYPOMELANOSES OF HAIR AND SKIN Jean-Paul Ortonne, David B Mosher, and Thomas B Fitzpatrick Vitiligo and Other Hypomelanoses of Hair and Skin Jean-Paul Ortonne, M.D.. .Vitiligo and Other Hypomelanoses of H air and Skin TOPICS IN DERMA TOLOGY Series Editors: John A Parrish and Thomas B Fitzpatrick Harvard Medical School, Boston, Massachusetts VITILIGO AND OTHER