Acta Dermato-Venereologica 99-4CompleteContent | Page 6

360 REVIEW ARTICLE Skin Cancer Associated Genodermatoses: A Literature Review Juliane SCHIERBECK, Tine VESTERGAARD and Anette BYGUM Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark Skin cancer has become the most common type of can- cer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically predisposed to skin cancer and this article is intended as a diagnostic tool when encountering pa- tients with multiple skin cancer lesions. The disorders are described with clinical characteristics, genetics and management. The most common syndromes asso- ciated with basal cell carcinoma are: Gorlin–Goltz syn- drome, Rombo syndrome, and Bazex-Dupré-Christol syndrome. Multiple squamous cell carcinomas can be related to: xeroderma pigmentosum, Ferguson-Smith, Muir-Torre syndrome, Mibelli-type porokeratosis, keratitis-ichthyosis-deafness syndrome, Rothmund- Thomson syndrome, Bloom syndrome, and epidermo- dysplasia verruciformis. Malignant melanoma can be inherited, as in familial atypical multiple mole mela- noma syndrome. Key words: genodermatoses; skin cancer; basal cell carcinoma; squamous cell carcinoma; hereditary skin cancer. Accepted Jan 16, 2019; E-published Jan 17, 2019 Acta Derm Venereol 2019; 99: 360–369. Corr: Juliane Schierbeck, Department of Dermatology and Allergy Centre, Odense University Hospital, Vesterbro 116, 1th, DK-5000 Odense C, Den- mark. E-mail: [email protected] S kin cancer is the most common type of cancer world- wide, with more than 15,000 patients annually in Denmark (which has a population of ~5.8 million) (1). Skin cancer is often caused by environmental exposure to ultraviolet radiation (UVR), immunosuppressive therapy or radiotherapy. A small, and often overlooked, group of patients are ge- netically predisposed to develop skin cancer, sometimes associated with internal malignancies. These hereditary skin conditions, or genodermatoses, are often clustered, with multiple family members showing symptoms, al­ though de novo mutations are also not uncommon. Awa- reness of these disorders is therefore essential for early diagnosis and treatment, as well as for identification of potentially affected family members. Early identification and diagnosis is crucial to the outcome and prognosis. Skin symptoms are easier to recognize, whereas visceral malignancies are more difficult and slower to identify. The first healthcare practitioners to see and treat these patients are general practitioners and dermatologists, who have a responsibility in recognizing and facilita- ting further genetic investigations and primary care, as described below. doi: 10.2340/00015555-3123 Acta Derm Venereol 2019; 99: 360–369 SIGNIFICANCE This article reviews hereditary skin syndromes that cause an increased risk of skin cancer development. It is im- portant for physicians treating skin cancer to be aware of hereditary causes, especially when examining patients with multiple cancerous lesions with no obvious explanation. This article describes clinical features, genetic descriptions and management suggestions for hereditary syndromes associated with skin cancer, and includes clinical images from our practice. This literature review focuses on hereditary causes of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). The review will serve as a tool in diagnosing and treating patients with multiple skin cancers. HEREDITARY BASAL CELL CARCINOMA Gorlin–Goltz syndrome Gorlin–Goltz syndrome (GGS), also known as Gorlin syndrome, naevoid basal cell carcinoma syndrome or multiple naevoid basal cell epithelioma, jaw cysts and bifid rib syndrome, is an autosomal dominant condi- tion causing unusual facial appearances (mandibular prognathia, lateral displacement of the inner canthus, frontal and biparietal bossing), dental cysts, palmar pits and a predisposition for BCC. Other cardinal features are calcification of the falx cerebri, medulloblastoma, kyphoscoliosis, rib anomalies, cleft lip/palate, eye ano- malies, milia and syndactyly (2). Two major and 1 minor criteria or 1 major and 3 minor criteria are necessary to determine the diagnosis, as shown in Table I. Binkley & Johnson were the first to suggest a correla- tion between dental cysts, partial agenesis of the corpus callosum, a bifid rib, an ovarian fibroma and epithelioma adenoides cysticum in 1951 (3). It was, however, the oral pathologist and human geneticist Robert J. Gorlin and the dermatologist Robert Goltz, who, in 1960, published and described the specific syndrome, which consists of multiple naevoid basal cell epitheliomas, jaw cysts and bifid ribs (4). Molecular genetics and pathophysiology. Recent studies in molecular genetics have proven GGS to be caused by mutations in the PTCH1 gene on chromosome 9q22, the PTCH2 gene on chromosome 1p32, or the SUFU gene on chromosome 10q24-q25, encoding for proteins in the This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.