Frederick C Morgan1, Lamis Yehia2, Christine McDonald3, Julian A Martinez-Agosto4, Antonio Y Hardan5, Joan Tamburro6, Mustafa Sahin7, Cheryl Bayart8, Charis Eng9. 1. Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio. 2. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. 3. Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. 4. Department of Human Genetics, UCLA, Los Angeles, California. 5. Department of Child Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California. 6. Department of Dermatology, Cleveland Clinic, Cleveland, Ohio. 7. Translational Neurosciences Center, Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts. 8. Department of Dermatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: cheryl.bayart@cchmc.org. 9. Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Center for Personalized Genetic Healthcare, Community Care and Population Health, Cleveland Clinic, Cleveland, Ohio; Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio; Germline High Risk Cancer Focus Group, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio. Electronic address: engc@ccf.org.
Abstract
BACKGROUND: Dermatologic phenotypes in PTEN hamartoma tumor syndrome (PHTS) are heterogeneous and poorly documented. OBJECTIVE: To characterize dermatologic findings among PHTS and conduct an analysis of genotype-dermatologic phenotype associations. METHODS: Mucocutaneous findings were reviewed in a multicenter cohort study of PHTS. Genotype-dermatologic phenotype associations were tested using multivariable regression. RESULTS: A total of 201 patients were included. Children were significantly less likely than adults to have oral papillomas, vascular malformations, benign follicular neoplasms, and acral keratoses. There were no cases of skin cancer among children. Basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma developed in 5%, 2%, and 1% of White adults, respectively. After adjusting for age, missense mutations were associated with 60% lower odds of developing cutaneous papillomatous papules (odds ratio: 0.4; 95% confidence interval [0.2, 0.7]), oral papillomas (0.4; 95% confidence interval [0.2, 0.9]), and vascular malformations (0.4; 95% confidence interval [0.2, 0.8]). LIMITATIONS: Partly retrospective data. CONCLUSION: Children are less likely than adults to have certain dermatologic findings, likely due to age-related penetrance. The risk of pediatric melanoma and the lifetime risk of nonmelanoma skin cancer in PHTS may not be elevated. Missense variants may be associated with the development of fewer dermatologic findings but future validation is required.
BACKGROUND: Dermatologic phenotypes in PTEN hamartoma tumor syndrome (PHTS) are heterogeneous and poorly documented. OBJECTIVE: To characterize dermatologic findings among PHTS and conduct an analysis of genotype-dermatologic phenotype associations. METHODS: Mucocutaneous findings were reviewed in a multicenter cohort study of PHTS. Genotype-dermatologic phenotype associations were tested using multivariable regression. RESULTS: A total of 201 patients were included. Children were significantly less likely than adults to have oral papillomas, vascular malformations, benign follicular neoplasms, and acral keratoses. There were no cases of skin cancer among children. Basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma developed in 5%, 2%, and 1% of White adults, respectively. After adjusting for age, missense mutations were associated with 60% lower odds of developing cutaneous papillomatous papules (odds ratio: 0.4; 95% confidence interval [0.2, 0.7]), oral papillomas (0.4; 95% confidence interval [0.2, 0.9]), and vascular malformations (0.4; 95% confidence interval [0.2, 0.8]). LIMITATIONS: Partly retrospective data. CONCLUSION: Children are less likely than adults to have certain dermatologic findings, likely due to age-related penetrance. The risk of pediatric melanoma and the lifetime risk of nonmelanoma skin cancer in PHTS may not be elevated. Missense variants may be associated with the development of fewer dermatologic findings but future validation is required.
Authors: Mark A Scheper; Nikolaos G Nikitakis; Eleni Sarlani; John J Sauk; Timothy F Meiller Journal: Oral Surg Oral Med Oral Pathol Oral Radiol Endod Date: 2006-01-10
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