==== Front Ann Saudi MedAnn Saudi MedAnnals of Saudi Medicine0256-49470975-4466King Faisal Specialist Hospital and Research Centre 1839827310.5144/0256-4947.2008.132asm-2-132Case ReportSkin tags as a presenting sign of basal cell nevus syndrome in three sisters of the same family Alghamdi Yousef From Adama Clinics, Jeddah, Saudi ArabiaCorrespondence and reprints: Yousef Alghamdi, MD, Dermatology, Adama Clinics, Altahleyah Street, Jeddah, PO Box 51454, Jeddah 21543, Saudi Arabia, T: +9662-660-0000, F: +9662-667-9898, dryousefmd@yahoo.comMar-Apr 2008 28 2 132 134 01 7 2007 Copyright © 2008, Annals of Saudi Medicine2008This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. ==== Body Basal cell nevus syndrome (BCNS), which is also known as nevoid basal cell carcinoma, Gorlin’s syndrome, and MIM 109400 (Mendelian Inheritance in Man), is an autosomal dominant genodermatosis characterized mainly by the presence of multiple basal cell carcinomas (BCCs), jaw cysts, and palmoplantar pits.1 It was first described by Jarish and White in 1894,1 but its syndromic nature was not defined until 1960 by Gorlin and Goltz.2 The PTCH 1 gene, the human homologue of the Drosophila patched polarity gene, has been shown to be involved in the development of BCNS3–5 with some cases appearing as spontaneous mutations of the same gene.6 In this article we describe three sisters of different ages with an almost exactly identical presentation. Their main complaint was multiple skin tag-like papules on the skin. Case 1 A 10-year-old girl presented to the dermatology clinic with a complaint of an increasing number of skin tags since the age of 4 (Figure 1, 2). Many dermatologists had seen her and the condition was misdiagnosed as skin tags, warts, and nevi. No skin biopsy had been done before from the skin tags. The medical history revealed hydrocephalus since birth for which she had undergone a shunt operation. She had borderline mental retardation with learning disability; she was still in the first grade. Physical examination showed multiple skin-colored to brownish soft papules; some were pedunculated, located on the face, neck, trunk, axillae and extremities. She had multiple small 0.5–1 mm palmoplantar pits. She also had characteristic phenotypic abnormalities: macrocephaly, bossing of the skull, a broad nasal root, ocular hypertelorism, scleral melanocytosis, high arched palate, uplifting of the nose, and narrow sloping shoulders. Other aspects of the physical examination were unremarkable. Radiological examination of the skull revealed hydrocephalus, calcification of the falx cerebri in addition to the ventriculoperitoneal shunt tube. X-ray of the hands revealed shortening of the fourth metacarpal bone. Other aspects of the radiographic survey were unremarkable. Panoramic x-ray of the mandible revealed no jaw cysts. A skin biopsy found follicular basal cell carcinoma (BCC) (Figure 3). The patient was treated by snipping off those pedunculated lesions followed by cryotherapy to the base to minimize scarring. In addition, the patient was provided with photoprotection and genetic counseling. Cases 2 and 3 An 8-year-old sister of the patient described in case 1 presented in exactly the same way with skin tags, hydrocephalus, a shunt operation, characteristic facies and palmoplantar pits. She was dropped from school because of poor performance. A 6-year-old sister of the previous 2 patients, presented with only multiple skin tags and palmoplantar pits. There was no hydrocephalus yet she had a characteristic facies as well. Cases 2 and 3 did not come back for further investigation. The parents were first-degree relatives, but there were no similar problems in them or in their families. DISCUSSION BCNS is a genodermatosis transmitted as an autosomal dominant trait exhibiting high penetrance and variable expressivity, mapped to chromosome 9q22.3-31.7,8 Inherited or spontaneous mutations in the human homologue of the Drosophila patched gene underlie the disorder.7 The diagnosis of BCNS relies mostly on the clinical features. Table 1 summarizes both major and minor features of this syndrome.9 For diagnosis we need at least two major features, or one major feature and an affected first-degree relative or two minor features and an affected first-degree relative, or multiple BCCs in childhood.6,10,11 The main complaint of the patients was the presence of multiple skin tag-like papules that were increasing in number. Skin tags are benign fibroepithelial polyps and are distinctly uncommon in this age group. Our cases developed many of the features of this syndrome early in life, with hydrocephalus, characteristic facie, palmoplantar pits, and skin tag-like lesions being among the early manifestations. Despite the fact that they were not twins, they developed almost exactly the same features. Nomland described skin tags in association with this syndrome and used the term “nevus of basal cell”.12 Elvira Chiritescu et al described 7 children with the same presentation. Multiple skin tags in this age group could represent an early sign for BCNS.11 The first case also had scleral melanocytosis, which had not been reported before with BCNS; whether it is part of the syndrome or just an isolated finding is not known. BCCs develop much more in sun-exposed areas,13,14 especially the head and neck. Thus, a high index of suspicion and early detection of this syndrome could help in the proper management of those cases. Early use of sunscreen could decrease the number of BCCs and/or prevent aggressive growth. Patients with BCNS should be followed closely and therapy must be directed at the individual lesions as they arise, most importantly tumors. BCCs could be treated with different modalities, cryotherapy being the least scarring. Delta-aminolevulinic acid and blue light photodynamic therapy and 5-aminolevulinic acid photodynamic therapy were reported to be successful in the treatment of multiple BCCs in BCNS with an excellent cosmetic outcome.15,16 Other modalities of treatment include electrocautery, excisions, topical imiquimod, 17 and CO2 laser resurfacing.18 Genetic counseling is important as the disease is autosomal dominant and any child of an affected family is at 50% risk of carrying the affected gene and developing the disease.19–22 In conclusion, we need to have a high index of suspension to diagnose these rare syndromes as early diagnosis and genetic counseling could prevent major consequences. Figure 1 Case 1 showing characteristic phenotype with bossing of the skull, hypertelorism, broad nasal root, up-lifting of the nose, and a few dark brown skin tag-like lesions on the face and neck. Figure 2 Same case with multiple dark brown skin tag-like papules on the back. Figure 3 (a,b) Basal cell carcinoma, follicular type from Case 1. (Hematoxylin-eosin stain) Table 1 Diagnostic criteria of basal cell nevus syndrome.6,9–11 Major features Multiple basal cell carcinomas Basal cell carcinoma before age 20 Odontokeratogenic cysts confirmed by histology Palmar or plantar pits (>3) Bilamellar clarification of falx cerebri Positive family history Minor features Congenital skeletal anomaly Macrocephaly Cardiac or ovarian fibroma Medulloblastoma Lymphomesenteric cysts Congenital malformations ==== Refs REFERENCES 1 Howell JB Caro MR The Basal-Cell Nevus: Its relationship to multiple cutaneous cancers and associated anomalies of development Arch Dermatol 1959 79 67 80 2 Gorlin RJ Nevoid Basal Cell Carcinoma Syndrome Medicine 1987 66 98 113 3547011 3 Hahn H Wicking C Zaphiropoulos PG Gailani MR Shanley S Chidambaram A Mutations of the human homologue of Drosophila Patched in the Nevoid Basal Cell Carcinoma Syndrome Cell 1996 85 841 8681379 4 Johnson RL Rothman AL Xie J Goodrich LV Bare JW Bonifas JM Human homologue of Patched, a candidate gene for the Basal Cell Nevus Syndrome Science 1996 272 1668 8658145 5 Wolter M Reifenberger J Sommer C Ruzicka T Reifenberger G Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinoma of the skin and primitive neuroectodermal tumors of the central nervous system Cancer Res 1997 57 2581 2585 9205058 6 Shanley S Ratcliffe J Hockey A Haan E Oley C Ravine D Nevoid Basal Cell Carcinoma Syndrome: review of 118 affected individuals Am J Med Genet 1994 50 282 90 8042673 7 High A Zedan W Basal Cell Nevus Syndrome Curr Opin Oncol 2005 3 17 2 160 166 15725922 8 Unden AB Stahle-Backdahl M Holmberg E Larsson C Toftgard R The mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q Acta Derm Venereol 1997 77 4 9 9059667 9 Crawford Capt Kevin M MD Kobayashi Maj Todd MD Nevoid basal cell carcinoma syndrome or multiple hereditary infundibulocystic basal cell carcinoma syndrome J Am Acad Dermatol 2004 51 989 995 15583598 10 Kimonis VE Goldstein AM Pastakia B Yang ML Kaas R DiGiovanna JJ Clinical Manifestations in 105 persons with nevoid basal cell carcinoma syndrome Am J Med Genet 1997 69 299 308 9096761 11 Chiritescu E Maloney ME Acrocordons as a presenting sign of nevoid basal cell carcinoma syndrome J Am Acad Dermatol 2001 44 789 794 11312426 12 Nomland R Multiple basal cell epithelioma originating from congenital pigmented basal cell nevi Arch Dermatol Syphilol 1932 25 1002 1008 13 Howell JB Nevoid basal cell carcinoma syndrome: Profile of genetic & environmental factors in oncogenesis J Am Acad Dermatol 1984 11 98 104 6736355 14 Goldstein AM Bale SJ Peck GL DiGiovanna JJ Sun exposure and basal cell carcinomas in the nevoid basal cell carcinoma syndrome J Am Acad Dermatol 1993 7 29 1 34 41 8315076 15 Itkin A Gilchrest BA Delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinoma in two patients with nevoid basal cell carcinoma syndrome Dermatol Surg 2004 7 30 7 1054 1061 15209801 16 Oseroff AR Shieh S Frawley NP Cheney R Blumenson LE Pivnick EK Bellnier DA Treatment of diffuse basal cell carcinomas and basaloid follicular hamartomas in nevoid basal cell carcinoma syndrome by wide-area 5-aminolevulinic acid photodynamic therapy Arch Dermatol 2005 1 141 1 60 67 15655143 17 Vereecken P Monsieur E Petein M Heenen M Topical application of imiquimod for the treatment of high-risk facial basal cell carcinoma in Gorlin Syndrome J Dermatolg Treat 2004 4 15 2 120 121 18 Doctoroff A Oberlender SA Purcell SM Fullface carbon dioxide laser resurfacing in the management of a patient with the nevoid basal cell carcinoma syndrome Dermatol Surg 2003 12 29 12 1236 1240 14725671 19 Chung CH Wong TW Shieh TY Shieh DB Chao SC Nevoid Basal Cell Carcinoma Syndrome clinical manifestations & mutation analysis of a Taiwanese family J Formos Med Assoc 2003 11 102 11 793 797 14724726 20 Petrikovsky BM Bialer MG McLaughlin JA Bale AE Sonographic and DNA-Based prenatal detection of Gorlin Syndrome J Ultrasound Med 1996 6 15 6 493 495 8738998 21 Bialer MG Gailani MR McLaughlin JA Petrikovsky B Bale AE Prenatal diagnosis of Gorlin Syndrome Lancet 1994 8 13 344 22 Hogge WA Blank C Roochvarg LB Hogge JS Wulfsberg FA Raffel LJ Gorlin Syndrome (nevoid basal cell carcinoma syndrome): Prenatal detection in a fetus with macrocephaly and ventriculomegaly Prenat Diagn 1994 8 14 8 725 727 7991513