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Caso Clnico / Case Report

Sndrome de Proteus: relato de caso * Proteus syndrome: a case report *


Nara Regina Nunes Vieira 1 Cludia Mrcia Resende Silva 2 Luciana Baptista Pereira 3 Bernardo Gontijo 4

Resumo: A sndrome de Proteus considerada hamartomatose congnita que afeta os trs folhetos embrionrios, acarretando o crescimento excessivo dos tecidos. Os autores descrevem um caso dessa sndrome rara. Trata-se de uma criana do sexo masculino portadora desde o nascimento de hiperplasia cerebriforme plantar, gigantismo do p esquerdo, mancha em vinho do Porto, linfangioma e macrocefalia, entre outras caractersticas tipicamente descritas nessa sndrome, que apresenta grande polimorfismo clnico e evolutivo. Palavras-chave: Anormalidades mltiplas; hamartoma; sndrome de Proteus. Summary: Proteus syndrome is considered the congenital hamartomatosis that affects the three germ layers and results in excessive tissue growth. The authors report a case of this rare entity. The patient was a male child born with plantar cerebriform hyperplasia, left foot gigantism, port-wine stains, lym phangioma, cranial macrocephaly and other characteristics typically described in this syndrome that displays great polymorphism in its presentation and clinical course. Key words: Abnormalities, multiple; hamartoma; Proteus syndrome.

INTRODUO A sndrome de Proteus foi reconhecida pela primeira vez como entidade nosolgica distinta em 1979 por Cohen e Hayden, que a descreveram como uma nova sndrome hamartomatosa.1 Em 1983 Wiedeman2 props o nome sndrome de Proteus para essa doena, descrevendo quatro casos com as seguintes caractersticas: gigantismo parcial das mos e dos ps, nevo pigmentado, hemi-hipertrofia, tumores subcutneos, macrocefalia e outras anomalias cranianas e viscerais. O nome deriva do deus grego Proteus, capaz de alterar sua forma para evitar ser capturado. Essa denominao muito oportuna, visto que a sndrome se caracteriza por grandes variaes morfolgicas em sua apre-

INTRODUCTION Proteus syndrome was recognized for the first time as a different nosologic entity in 1979, by Cohen and Hayden, who described it as a new hamartomatosa syndrome.1 In 1983, Wiedeman2 proposed the name Proteus syndrome for this disease, describing four cases with the following characteristics: partial gigantism of the hands and feet, pigmented nevi, hemihypertrophy, subcutaneous tumors, macrocephaly and other cranial and visceral anomalies. The name is derived from the Greek god Proteus, capable of altering his form in order to avoid being captured. This denomination is very opportune, since the syndrome is characterized by great morphologic

Recebido em 10.6.1999. / Received in June, 10th of 1999. Aprovado pelo Conselho Consultivo e aceito para publicao em 26.1.2001. / Approved by the Consultive Council and accepted for publication in January, 26th of 2001. * Trabalho realizado no Servio de Dermatologia do Hospital das Clnicas, Faculdade de Medicina da UFMG. / Work done at the Dermatology Service of the Hospital das Clnicas, Faculdade de Medicina da UFMG. Residente de Dermatologia. / Resident of Dermatology. Mdica, Ambulatrio de Dermatologia. / Doctor, Dermatology Ambulatory. Professora Assistente de Dermatologia UFMG. Docente, Ambulatrio de Dermatologia Peditrica, Hospital Central UFMG. / Assistant Professor of Dermatology UFMG. Teacher, Clinic of Pediatric Dermatology, Central Hospital UFMG. 4 Professor Adjunto de Dermatologia UFMG. Coordenador, Ambulatrio de Dermatologia Peditrica, Hospital Central UFMG. / Adjunct Professor of Dermatology UFMG. Coordinator, Pediatric Dermatology Ambulatory, Central Hospital UFMG.
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2001 by Anais Brasileiros de Dermatologia

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sentao e evoluo. Por exemplo, crianas com essa sndrome podem ser normais ao nascimento e, mais tarde, apresentar todos os critrios diagnsticos.3 Cerca de 67 casos foram descritos na literatura de lngua inglesa at fevereiro de 1997.4,5 O mais conhecido o de Joseph Merrick (cuja histria foi contada no livro e filme O homem elefante) aceito desde 1988, aps os estudos de Cohen, como sndrome de Proteus, e no de neurofibromatose, como se acreditava.6,7 Neste relato apresentado um caso de sndrome de Proteus com os seguintes critrios diagnsticos: hiperplasia cerebriforme plantar esquerda, gigantismo do p esquerdo, linfangioma, macrocefalia, assimetria facial e do crnio, palato ogival, hipoplasia dentria, orelhas em abano, sindactilia parcial e mancha em vinho do Porto. O diagnstico diferencial principal neste caso se faz com a sndrome de Klippel-Trenaunay-Weber, considerada por alguns autores uma forma localizada da sndrome de Proteus. RELATO DO CASO Paciente de quatro anos, do sexo masculino, faiodrmico, natural e residente em Contagem, MG, apresentando desde o nascimento mcula angiomatosa (mancha em vinho do Porto), bem delimitada, com bordas irregulares, no hemitrax e hemiabdmen esquerdos, perna e brao esquerdos (Figura 1). Verificaram-se, tambm, membro inferior esquerdo com volume aumentado (Figura 2), hiperplasia cerebriforme plantar esquerda (Figura 3), veias proeminentes no tronco, linfangiomas no abdmen e coxa esquerda (Figura 4) e angioceratomas na perna e p esquerdos (Figura 5). O desenvolvimento neuropsicomotor demonstrava-se atrasado, com retardo mental leve.

variations in its presentation and clinical course. For instance, children with the syndrome can be normal at birth, yet later present all of the diagnostic criteria.3 The literature contains descriptions of some 67 cases written in the English language up until February 1997.4,5 The most well known is that of Joseph Merrick (whose story is told in the book and film The elephant man). Since 1988, after Cohen's studies it was accepted that he had Proteus syndrome and not neurofibromatosis, as was previously believed.6,7 In this report, a case of Proteus syndrome is presented with the following diagnostic criteria: left plantar cerebriform hyperplasia, gigantism of the left foot, lymphangioma, macrocephaly, facial and cranial asymmetry, ogival palate, dental hypoplasia, protuberant ears, partial syndactyly and Portwine stains. The main differential diagnosis in this case is made with Klippel-Trenaunay-Weber syndrome, considered by some authors to be a localized form of Proteus syndrome. CASE REPORT Patient, four years old, male, mulatto, natural and resident in Contagem, MG, presented since birth angiomatous maculae (Port-wine stains), well delimited, with irregular borders, on the hemithorax and left hemiabdomen, left leg and arm (Figure 1). Examination also showed left lower member with increased volume (Figure 2), left plantar cerebriform hyperplasia (Figure 3), prominent veins in the trunk, lymphangiomas in the abdomen and left thigh (Figure 4) and angiokeratomas in the leg and left foot (Figure 5). Neuropsychomotor development was demonstrably late, with slight mental retardation.

Figura 1: Mcula angiomatosa com bordas irregulares no hemitrax e hemiabdmen esquerdo (tambm presente na perna e brao esquerdo) Figure 1: Angiomatous macula with irregular borders on the left hemithorax and hemiabdomen (also present on left leg and arm) An bras Dermatol, Rio de Janeiro, 76(2):201-208, mar./abr. 2001.

Figura 2: Aumento do volume do membro inferior esquerdo Figure 2: Increased volume of left lower member

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Figura 3: Hiperplasia cerebriforme plantar Figure 3: Plantar cerebriform hyperplasia

Figura 4: Linfangiomas na coxa esquerda Figure 4: Lymphangiomas in the left thigh

Apresentava tambm assimetria craniana, fronte olmpica, macrocefalia (percentil > 95), orelhas em abano, palato ogival, hipoplasia dentria, sindactilia do segundo e do terceiro dedos do p esquerdo, membro inferior esquerdo menor do que o direito (2cm) e testculos retrados. No havia visceromegalias. O paciente no apresentava alteraes na avaliao oftalmolgica. Tratava-se de caso nico na famlia, sem consanginidade entre os pais. Em relao aos exames complementares, havia aumento do dimetro anteroposterior do crnio (dolicocefalia) na radiografia simples. A tomografia computadorizada do crnio mostrava assimetria da calota craniana, rea sugestiva de angiomatose na regio frontal bilateral e exuberncia de veia perimesenceflica esquerda. As angiografias cerebral e vertebral foram normais, assim como a ultrasonografia abdominal. Na radiografia simples da perna e do p esquerdos havia aumento das partes moles e estrutura ssea normal. O dupplex scan do membro inferior esquerdo no revelou fstulas arteriovenosas e malformao vascular. Os exames histopatolgicos das leses cutneas caracterizaram angioceratoma (perna esquerda) e hemangioma cavernoso (infra-axilar esquerda). A criana evoluiu com alguns episdios de erisipela no membro inferior esquerdo, tratados com antibiticos, e

He also presented cranial asymmetry, Olympic forehead, macrocephaly (percentile > 95), protuberant ears, ogival palate, dental hypoplasia, syndactyly of the left second and third toes, left lower member smaller than the right (2cm) and retracted testicles. There was no visceromegaly and the patient did not present alterations in the ophthalmologic evaluation. This was the only case in the family and there was no consanguinity between the parents. In relation to the complementary exams, there was an increase in the anteroposterior diameter of the skull (dolichocephaly) in the simple x-ray. Computerized tomography of the skull showed asymmetry of the cranium, an area suggestive of angiomatosis in the bilateral front area and exuberance of the left perimesencephalic. Cerebral and vertebral angiography were normal, as well as the abdominal ultrasound scan. Simple x-ray of the leg and left foot showed increase in the soft parts and normal bone structure. Duplex scan of the left lower member did not detect arteriovenous fistulae or vascular malformation. Histopathological exams of the cutaneous lesions characterized angiokeratoma (left leg) and cavernous hemangioma (left infra-axillary). The child coursed with some episodes of erysipelas in the left lower member, treated with antibiotics, and is being

Figura 5: Angioceratomas no p esquerdo An bras Dermatol, Rio de Janeiro, 76(2):201-208, mar./abr. 2001.

Figure 5: Angiokeratomas on left foot

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est sendo acompanhada no Servio de Dermatologia do Hospital das Clnicas da UFMG, tendo sido submetida criocirurgia com nitrognio lquido para tratamento das leses de angioceratoma, com boa resposta, e antibiticos para infeces no membro inferior esquerdo, quando necessrio. DISCUSSO A doena considerada hamartomatose congnita que afeta os trs folhetos embrionrios e tem como resultado o crescimento excessivo dos tecidos. No h alterao na secreo do hormnio do crescimento, mas parece haver distrbios na produo dos fatores de crescimento insulinalike e das protenas de ligao plasmtica desses fatores nos tecidos acometidos.7 A causa desconhecida, no tendo sido observado nenhum tipo de herana. Quase todos os casos so espordicos, com apenas dois casos de possvel transmisso da sndrome de pais para filhos.1,8 Estudos citogenticos de rotina no tm demonstrado alteraes cromossmicas, sugerindo que a sndrome seja resultado de mosaicismo por mutao somtica (o gene autossmico dominante homozigtico seria letal).1 O caritipo de um paciente mostrou segmento adicional no brao longo do cromossomo 1 (Cr 1q).4,8 Constituem evidncias de mosaicismo somtico a ocorrncia espordica, sem predileo por sexo, a distribuio das leses em mosaico e sua extenso varivel, porm jamais envolvendo toda a superfcie corprea.1 No paciente em questo a ocorrncia foi espordica, sem outros casos na famlia. As leses no acometiam a superfcie corprea total e, sim, um porte lateral, mas eram bastante variveis morfolgica e histologicamente. Existem vrios critrios diagnsticos propostos.2,5,7 Em 1989 Samlaska7 sugeriu sete critrios maiores 1. gigantismo das mos e/ou dos ps; 2. nevo pigmentado; 3. hemi-hipertrofia; 4. tumores subcutneos; 5. anomalias cranianas; 6. crescimento acelerado; e 7. anomalias viscerais , sendo necessrios pelo menos quatro deles para o diagnstico (Quadro 1). Desses, o paciente apresenta gigantismo do p esquerdo com massa plantar esquerda, hemi-hipertrofia parcial esquerda, tumores subcutneos e anomalias cranianas. Dentre as anomalias associadas destacam-se as cutneas, esquelticas e craniofaciais. O paciente apresenta mancha angiomatosa na superfcie corporal esquerda, orelhas em abano, palato ogival, hipoplasia dentria e sindactilia de pododctilos esquerdos apresenta, portanto, quatro alteraes maiores e cinco associadas. Os critrios diagnsticos propostos por DarmstadtLane em 19945 constam do quadro 2. O paciente apresenta os seguintes critrios: gigantismo do p esquerdo (cinco pontos), hiperplasia cerebriforme plantar esquerda (quatro pontos), tumores subcutneos linfangioma (quatro pontos), macrocefalia (dois pontos e meio), assimetria facial (um ponto), assimetria do crnio (um ponto), palato ogival (um ponto), hipoplasia
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followed up at the Dermatology Service of the Hospital das Clnicas, UFMG, after having been submitted to cryosurgery with liquid nitrogen for treatment of the angiokeratoma lesions, with good response, and antibiotics for infections in the left lower member when necessary. DISCUSSION The disease is considered congenital hamartomatosis that affects the three germ layers and results in excessive tissue growth. There is no alteration in the secretion of the growth hormone, but there appears to be some disorder in the production of the insulin-like growth factors and proteins with plasmatic binding to these factors in the involved tissues.7 The cause is unknown and no type of inheritance has been observed. Almost all of the cases are sporadic, with only two cases of possible transmission of the syndrome from parent to children.1,8 Routine cytogenetic studies have not demonstrated any chromosomal alterations, suggesting that the syndrome is a result of mosaicism by somatic mutation (the dominant homozygous autosomal gene would be lethal).1 The karyotype of one patient showed an additional segment in the long arm of the chromosome 1 (Cr 1q).4,8 The sporadic occurrence, without sex bias, mosaic distribution of the lesions and their variable extension, although never involving the whole body surface constitute evidence of somatic mosaicism.1 In the patient in question, the occurrence was sporadic, without other cases in the family. The lesions did not involve the entire corporal surface, but the left side, although they were very variable in morphologic and histologic terms. Various diagnostic criteria have been proposed.2,5,7 In 1989, Samlaska7 suggested seven major criteria 1. gigantism of the hands and/or feet; 2. pigmented nevi; 3. hemihypertrophy; 4. subcutaneous tumors; 5. cranial anomalies; 6. accelerated growth; and 7. visceral anomalies, with at least four of these being present to confirm the diagnosis (Table 1). Of these, the patient presented gigantism of the left foot with left plantar mass, partial left hemihypertrophy, subcutaneous tumors and cranial anomalies. Among the associated anomalies, the cutaneous, skeletal and craniofacial aspects are highlighted. The patient presented angiomatous stain in the left side of the body, protuberant ears, ogival palate, dental hypoplasia and syndactyly of the left toes- thereby presenting four major and five associated alterations. The diagnostic criteria proposed by Darmstadt-Lane in 19945 are shown in Table 2. The patient presented the following criteria: gigantism of the left foot (five points), cerebriform left plantar hyperplasia (four points), subcutaneous tumors lymphangioma (four points), macrocephaly (two and a half points), facial asymmetry (one point), asymmetry

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Quadro 1: Caractersticas clnicas maiores e ocasionais da Sndrome de Proteu, propostas por Samlaska em 1989 Table 1: Major and occasional clinical characteristics of Proteus syndrome, as proposed by Samlaska in 1989
Caracterstica / Characteristic Maiores / Major Hemi-hipertrofia (parcial ou completa) / Hemihypertrophy (partial or complete) Macrodactilia / Macrodactyly Massas subcutneas (lipomatose, lipomatose plvica, hamartomas, hemangioma cavernoso) / Subcutaneous mass (lipomatosis, pelvic lipomatosis, 'hamartomas', cavernous hemangioma) Massas plantares ou palmares (nevo do tecido conjuntivo, lipomatose) / Plantar or palmar mass (nevus of the conjunctive tissue, lipomatosis) Exostose (craniana, extremidades distais) / Exostosis (cranial, distal extremities) Nevo epidrmico (linear, espiralado) / Epidermal nevus (linear, spiral) Escoliose / Scoliosis Ocasionais / Occasional Cutneas (varicosidades, manchas caf com leite, angioceratoma, fibroma, etc.) / Cutaneous (varicosity, caf au lait stains, angiokeratoma, fibroma, etc.) Esquelticas (macrocefalia, geno valgo, etc.) / Skeletal (macrocephaly, genu valgum, etc.) Crnio-facial (estrabismo, palato ogival, prognatismo mandibular, etc.) / Craniofacial (strabismus, ogival palate, mandibular prognathism, etc.) Miscelnea (retardo mental, atrofia muscular, cistos pulmonares, etc.) / Miscellaneous (mental retardation, muscular atrophy, pulmonary cysts, etc.)

dentria (um ponto), sindactilia parcial (um ponto), mancha em vinho do Porto (um ponto), totalizando mais de 21,5 pontos. Anomalias sistmicas so mais raras, sendo descritos cistos pulmonares,9 malformao cerebral com convulses, lipomas plvicos, hipertrofia renal, dilatao e hipertrofia da aorta, cistos ovarianos e genitlia ambgua.1,4,9 O paciente no apresenta malformao visceral, o que foi evidenciado pelos exames de imagem. A hiperplasia cerebriforme palmar e plantar um dos sinais mais caractersticos da sndrome e, de acordo com Clark et al., pode ser considerada patognomnica.1 Pode estar presente uni ou bilateralmente, sendo histologi-

of the skull (one point), ogival palate (one point), dental hypoplasia (one point), partial syndactyly (one point), Port-wine stains (one point), totaling over 21.5 points. Systemic anomalies are rarer and pulmonary cysts,9 cerebral malformation with convulsions, pelvic lipomas, renal hypertrophy, dilation and hypertrophy of the aorta, ovarian cysts and ambiguous genitalia have been described. 1,4,9 The patient did not present visceral malformation, as shown by the image exams. Palmar and plantar cerebriform hyperplasia is one of the most characteristic signs of the syndrome and according to Clark et al. can be considered pathognomonic.1 It may be unilaterally or bilaterally

Quadro 2: Caractersticas diagnsticas para a sndrome de Proteus e sua pontuao de acordo com a classificao proposta por Darmstadt-Lane em correspondncia ao caso apresentado Table 2: Diagnostic characteristics of Proteus syndrome and points according to the classification proposed by Darmstadt-Lane and corresponding to the current case report
Caractersticas / Characteristic Macrodactilia e/ou hemi-hipertrofia / Macrodactyly and/or hemihypertrophy Hiperplasia cerebriforme palmar ou plantar / Palmar or plantar cerebriform hyperplasia Tumores subcutneos e lipomas / Subcutaneous and lipomatous tumors Nevo epidrmico verrucoso / Verrucose epidermal nevus Exostose ou macrocefalia craniana / Exostosis or cranial macrocephaly Anormalidades menores / Lesser abnormalities Pontos / Points 5 4 4 3 2.5 1 Paciente / Patient + + + + +*

Para estabelecer o diagnstico so necessrios 13 pontos ou mais. * Assimetria craniana e facial, mancha em vinho do Porto, palato ogival, hipoplasia dentria, orelhas em abano, totalizando seis pontos / To establish the diagnosis, 13 or more points are necessary. * Cranial and facial asymmetry, Port-wine stain, ogival palate, dental hypoplasia, protuberant ears, sum up six points.

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camente caracterizada como um nevo do tecido conjuntivo ou lipomatoso. Alguns autores consideram que o diagnstico de sndrome de Proteus no pode ser feito apenas pela presena das massas plantares.7 A hemi-hipertrofia bastante comum, sendo observada neste caso. A macrodactilia e o crescimento acelerado so achados em 98% dos casos.5 Alguns autores descrevem o crescimento acelerado dos tecidos nos primeiros anos de vida. Quanto mais rpido e precoce esse crescimento, mais grave o caso.4,7 Outro achado bastante caracterstico diz respeito aos tumores subcutneos, com grande variedade histolgica. O paciente apresenta linfangioma e malformao vascular venosa (hemangioma cavernoso). Nevos epidrmicos verrucosos, lineares ou espiralados tambm podem estar presentes.4,5,7 As anomalias cranianas e faciais (macrocefalia, exostose, assimetria, palato ogival, prognatismo, m ocluso dentria, etc.) tambm foram notadas em grande nmero de pacientes.4,7,9 Neste caso, estavam presentes assimetrias craniana e facial, macrocefalia, palato ogival e hipoplasia dentria. A exostose do canal auditivo considerada, por alguns autores, patognomnica da sndrome de Proteus.1 Aproximadamente dois teros dos pacientes tm inteligncia normal, mas retardo mental pode-se associar s anomalias cranianas.4,5,9 O paciente apresentava retardo mental em associao s anomalias cranianas j descritas. Escoliose e cifoescoliose esto presentes em 50% dos pacientes.5,7 A sindactilia, apresentada pelo paciente em questo, foi descrita em alguns casos, assim como a polidactilia.10 A diminuio no tecido celular subcutneo e atrofia muscular das reas no envolvidas so comuns e talvez se devam a uma desnutrio secundria demanda tumoral.9 Outro achado importante a hipoplasia drmica com aparncia proeminente das veias, descrita por Happle.11 Ela poderia ser explicada por mecanismo gentico de twin spitting e empregada como critrio diagnstico, principalmente nos casos duvidosos. O paciente apresenta proeminncia das veias no tronco, principalmente na regio anterior. A transformao maligna dos hamartomas, de modo geral, risco bem conhecido, embora tenham sido relatados apenas dois casos de malignizao (um mesotelioma e um tumor testicular) relacionados com a sndrome de Proteus.5 Alteraes oftalmolgicas mais comumente observadas incluem exostose periorbital, catarata, coloboma de retina, hamartoma do segmento posterior, tumor epibulbar e telecanto.4 O exame oftalmolgico do paciente foi normal. H evidncias da existncia de formas localizadas dessa sndrome, sendo muito difcil fazer o diagnstico nesses casos. Um caso com mltiplas exostoses (craniana, facial e mandibular) e tumor na esclera,9 e outros dois com achado isolado de macrodactilia ao nascimento, sendo um deles associado sindactilia, foram descritos.12,13 Os principais diagnsticos diferenciais so:2,4,5,7,10,14,15,16 1. neurofibromatose tipo I: presena de massas tumorais
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present and histologically is characterized as nevus of the conjunctive or lipomatous tissue. Some authors consider that the diagnosis of Proteus syndrome cannot be based solely on the presence of plantar mass.7 Hemihypertrophy is quite common, and was observed in this case. Macrodactyly and accelerated growth are found in 98% of cases.5 Some authors have described accelerated tissue growth in the first years of life. The faster and more precocious this growth, the more serious the case.4,7 Another very characteristic finding concerns the subcutaneous tumors, which present a great histological variety. The patient presented lymphangioma and veined vascular malformation (cavernous hemangioma). Linear or spiral verrucose epidermal nevi can also be present.4,5,7 Cranial and facial anomalies (macrocephaly, exostosis, asymmetry, ogival palate, prognathism, dental malocclusion, etc. have also been observed in a great number of patients.4,7,9 In this case, cranial and facial asymmetries, macrocephaly, ogival palate and dental hypoplasia were present. Exostosis of the auditory channel is considered, by some authors, pathognomonic of Proteus syndrome.1 Approximately two thirds of the patients possess normal intelligence, but mental retardation can be associated with the cranial anomalies.4,5,9 The patient presented mental retardation in association with the above described cranial anomalies. Scoliosis and cyphoscoliosis are present in 50% of these patients.5,7 The syndactyly presented by the patient in question has also been described in other cases, as well as polydactyly.10 Decrease in the subcutaneous cellular tissue and muscular atrophy of non-involved areas are common and perhaps are due to malnutrition secondary to the tumoral demand.9 Another important finding is dermal hypoplasia with prominent appearance of the veins, as described by Happle.11 This could be explained by the genetic mechanism of twin splitting and used as a diagnostic criterion, especially in doubtful cases. The patient presented prominence of the veins in the trunk, mainly in the anterior region. In general, the malignant transformation of the hamartomas is a well-known risk, although only two cases of malignancy have been reported (one mesothelioma and a testicular tumor) in relation to Proteus syndrome.5 The most commonly observed ophthalmic alterations include periorbital exostosis, cataracts, coloboma of retina, hamartoma of the posterior segment, epibulbar tumor and telecanthus.4 The patient's ophthalmological exam was normal. There is evidence pointing to the existence of localized forms of this syndrome, though diagnosis is very difficult in such cases. A case with multiple exostosis (cranial, facial and mandibular) and tumor in the sclera,9 and another two with isolated finding of macrodactyly at birth, one of which in association with syndactyly, have been described.12,13 The main differential diagnoses are:2,4,5,7,10,14,15,16 1. type I neurofibromatosis: presence of subcutaneous

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subcutneas, neurofibromas, mculas caf-com-leite, eflides axilares, ndulos de Lisch e macrocefalia. A presena de hemi-hipertrofia e macrodactilia rara e geralmente ocorre pela presena de neuromas plexiformes; 2. sndrome de Klippel-Trenaunay-Weber: apresenta-se como hemi-hipertrofia, manchas em vinho do Porto, veias varicosas (geralmente unilaterais), malformaes arteriovenosas, bem como nevos epidrmicos. No ocorrem exostoses, hiperplasia cerebriforme plantar e crescimento acelerado. As formas localizadas da sndrome de Proteus so difceis de diferenciar dessa sndrome. No paciente apresentado, a ausncia de veias varicosas e de malformaes arteriovenosas, bem como a presena de hiperplasia cerebriforme plantar, confirma o diagnstico de sndrome de Proteus e no de Klippel-Trenaunay-Weber; 3. sndrome de Bannayan: doena com herana autossmica dominante composta de angiomatose, lipomatose, macrocefalia e risco aumentado de tumores intracranianos. Os pacientes no tm exostose craniana, nevo epidrmico, alteraes palmares e plantares, vistos na sndrome de Proteus; 4. lipomatose encfalo-crnio-cutnea: caracterizada por assimetria craniana, malformao ocular e craniana, calcificaes oculares, convulses, retardo mental, lipomas subcutneos no couro cabeludo com alopecia associada e lipomas cerebral e visceral. Embora seja considerada uma forma localizada da sndrome de Proteus, a maioria dos autores julga tratar-se de entidades distintas com manifestaes comuns; 5. outras sndromes que devem ser lembradas so a sndrome de Maffucci, a sndrome do nevo epidrmico e a discondroplasia de Ollier. O tratamento multidisciplinar, com suporte clnico e psicolgico. A remoo cirrgica dos tumores deve ser tentada no s nos casos com risco de complicaes (sangramento e obstruo), mas tambm naqueles inestticos. Essa correo deve ser feita o mais precocemente possvel a fim de proporcionar criana imagem corporal relativamente normal. O acompanhamento dos hamartomas, pelo risco de transformao maligna, deve ser realizado.2,3,4,5,9 A criana em questo est sendo acompanhada pelos servios de dermatologia, oftalmologia e gentica. Apresentou erisipela por duas vezes, sendo tratada com antibitico. As leses de angioceratoma foram tratadas com crioterapia com timo resultado. At o momento no foram detectadas alteraes sugestivas de malignidade em qualquer leso hamartomatosa. q

tumorous masses, neurofibromas, caf au lait macules, axillary ephelides, Lisch nodules and macrocephaly. The presence of hemihypertrophy and macrodactyly is rare and usually occurs due to the presence of plexiform neuromas; 2. Klippel-Trenaunay-Weber syndrome: presents as hemihypertrophy, Port-wine stains, varicose veins (usually unilateral), arteriovenous malformations, as well as epidermal nevi. Exostoses do not occur, nor does plantar cerebriform hyperplasia and accelerated growth. The localized forms of Proteus syndrome are difficult to differentiate from this syndrome. In the patient presented herein, the absence of varicose veins and arteriovenous malformations, as well as the presence of plantar cerebriform hyperplasia, confirms the diagnosis of Proteus syndrome rather than KlippelTrenaunay-Weber syndrome; 3. Bannayan syndrome: disease with dominant autosomal hereditary, composed of angiomatosis, lipomatosis, macrocephaly and increased risk of intracranial tumors. The patients do not have cranial exostosis, epidermal nevus, palmar and plantar alterations, as seen in Proteus syndrome; 4. cutaneous-cranial-encephalon lipomatosis: characterized by cranial asymmetry, ocular and cranial malformation, ocular calcifications, convulsions, mental retardation, subcutaneous lipomas in the scalp with associated alopecia and cerebral and visceral lipomas. Although considered a localized form of Proteus syndrome, the majority of authors judge these to be different entities with common manifestations; 5. other syndromes that should be kept in mind are Maffucci's syndrome, epidermal nevus syndrome and Ollier's dyschondroplasia. Treatment is multidisciplinary, with clinical and psychological support. Surgical removal of the tumors should be attempted in cases with risk of complications (bleeding and obstruction) and also for aesthetic reasons. This correction should be made as early as possible in order to provide the child a relatively normal corporal image. Follow up of the hamartomas should be realized due to the risk of malignant transformation.2,3,4,5,9 The child in question is being followed up by the dermatology, ophthalmology and genetics services. He presented erysipelas twice, which was treated with antibiotics. The angiokeratoma lesions were treated using cryotherapy with optimum results. To date, no alterations suggesting malignancy have been detected in any hamartomatosa lesion. q

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REFERNCIAS / REFERENCES
1. Cohen MM. Proteus syndrome: clinical evidence for somatic mosaicism and selective review. Am J Med Genet 1993;47:645-52. 2. Wiedemann HR, Burgio GR, Aldenhoff P, Kunze J, Kaufmann HJ, Schirg E. 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. 3. Alavi S, Chakrapani A, Kher A, Bharucha BA. The Proteus syndrome. J Postgrad Med 1993;39:219-21. 4. Barona-Mazuera MR, Hidalgo-Galvn LR, Orozco-Covarrubias ML et al. Proteus syndrome: new findings in seven patients. Pediatr Dermatol 1997;14:1-5. 5. Darmastd GL, Lane AT. Proteus syndrome. Pediatr Dermatol 1994;11:222-6. 6. Wallace MR. Elephant man's disease. Science 1994;264:188. 7. Samlaska CP, Levin SW, James WD et al. Proteus syndrome. Arch Dermatol 1989;125:1109-14. 8. Rudolph G, Blum WF, Jenne E et al. Growth hormone (GH), insulin-like growth factors (IGFs), and IGF- binding protein-3 (IGFBP-3) in a child with Proteus syndrome. Am J Med Genet 1994;50:204-10. 9. Vaughn RY, Selkinger AD, Howell CG, Parrish RA, Edgerton MT. Proteus syndrome; diagnosis and surgical manangement. J Pediatr Surg 1993;28:5-10. 10. Reardon W, Harding B, Winter RM, Baraitser M. Hemihypertrophy, hemimegalencephaly, and polydactyly. Am J Med Genet 1996;66:144-9. 11. Happle R, Steijlen PM, Theile U et al. Patch dermal hypoplasia as a characteristic feature of Proteus syndrome. Arch Dermatol 1997;133:77-80. 12. VanBever Y, Hennekam RCM. Isolated macrodactyly or extremely localized Proteus syndrome? Clin Dysmorphol 1994;3:351-2. 13. Lacombe D, Battin J. Isolated macrodactyly and Proteus syndrome. Clin Dysmorphol 1996;5:255-7. 14. Hagari Y, Aso M, Shimao S et al. Proteus syndrome: report of the first Japanese case with special reference to differentiation from Klippel-Trenaunay-Weber syndrome. J Dermatol 1992;19:477-80. 15. Martinez DN, Castillo V, Mckinster CD et al. Encefalocraniocutaneous lipomatosis: an uncommon neurocutaneous syndrome. J Am Acad Dermatol 1995;32:387-9. 16. Rizzo R, Pavone L, Micali G et al. Encephalocraniocutaneus lipomatosis, proteus syndrome, and somatic mosaicism. Am J Med Genet 1993;47:653-5.

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An bras Dermatol, Rio de Janeiro, 76(2):201-208, mar./abr. 2001.

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