Recognition of the phenotype of thalidomide embryopathy in countries endemic for leprosy: new cases and review of the main dysmorphological findings Fernanda S.L. Vianna a,b,c,d , Lavı ´nia Schu ¨ ler-Faccini a,b,c,d , Julio Ce ´ sar L. Leite c , Silvia H.C. de Sousa e , Lea Ma ´rcia M. da Costa f , Murilo F. Dias g , Elaine F. Morelo h , Maria Juliana R. Doriqui i , Claudia M. Maximino j and Maria Teresa V. Sanseverino a,b,c Thalidomide is the best-known teratogen worldwide. It was first marketed as a sedative in the late 1950s, but the birth of B10 000 children with birth defects resulted in the withdrawal of thalidomide from the market in 1962. Thalidomide embryopathy affects almost all organs but the main defects are concentrated in the limbs, eyes, ears, and heart. Shortly after the withdrawal of thalidomide from the market, its effectiveness in the treatment of erythema nodosum leprosum, an inflammatory condition resulting from leprosy, was reported and since the mid-1990s, the drug has been used widely in the treatment of cancers and autoimmune diseases, among other conditions. 40 000 new cases of leprosy are diagnosed every year in Brazil. Although there is a strict legislation for the prescription and use of thalidomide in Brazil, cases of thalidomide embryopathy have continued to be reported. Here, we present two new cases of thalidomide embryopathy identified in 2011 and review the major clinical findings in the literature that can aid the identification of the embryopathy. Clin Dysmorphol 22:59–63  c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Clinical Dysmorphology 2013, 22:59–63 Keywords: aberrant tears, embryopathy, heart disease, limb reduction defects, microphthalmia, thalidomide a INAGEMP – National Institute of Population Medical Genetics, b SIAT – Teratogen Information Service, c Medical Genetics Service, Hospital de Clinicas2de Porto Alegre, d Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, e Maternal and Child Hospital Complex of Maranha ˜ o, Maternity Dr Benedito Leite and Hospital Juvencio Mattos, f Department of Health, State of Maranha ˜o, g Maternal and Child Health Post Graduation Program, Federal University of Maranhao, Sao Luis, h National Leprosy Program – PNH, Health Vigilance Secretariat – SVS, Ministry of Health, i Department of Pharmacovigilance/National Sanitary Vigilance Agency – ANVISA, Brasilia DF and j Brazilian Association of People with Thalidomide Syndrome – ABPST, Sao Paulo, Brazil Correspondence to Lavı ´nia Schu ¨ ler-Faccini, Genetics Department – IB, Federal University of Rio Grande do Sul, Agronomy Campus, CP 15053, Postal Code 91501-970 Porto Alegre, RS, Brazil Fax: + 55 51 33598008/ + 55 519975-6770; e-mail: lavinia.faccini@ufrgs.br Received 17 October 2012 Accepted 8 February 2013 Introduction Thalidomide is the best-known teratogen worldwide. It was first marketed as a sedative in the late 1950s almost worldwide, but the birth of B10 000 children with birth defects resulted in the withdrawal of thalidomide from the market in 1962 (Lenz, 1988). Through evaluations carried out with a large number of patients, it was possible to describe thalidomide embryopathy. Almost all organs may be affected, but the main defects are concentrated in the limbs, eyes, ears, and heart (Lenz, 1988; Smithells and Newman, 1992). Shortly after the withdrawal of thalidomide from the market, Sheskin (1965) reported its effectiveness in the treatment of erythema nodosum leprosum (ENL), an inflammatory condition resulting from leprosy. He pre- scribed this drug to a leprosy patient as a sedative, and observed a complete improvement in symptoms and skin lesions within 3 days. Subsequently, clinical trials supported the efficacy of thalidomide in the treatment of ENL and it is currently one of the most effective treatments (Sheskin and Convit, 1969; Penna et al. , 2005; Kaur et al. , 2009). Also as a consequence of the efficacy in ENL, thalidomide’s anti-inflammatory (Sampaio et al. , 1991) and antiangiogenic properties (D’Amato et al. , 1994) were discovered, and since the mid-1990s, the drug has been used widely in the treatment of cancers and autoimmune diseases, among other conditions (Matthews and McCoy, 2003), and its use has expanded. Leprosy is a neglected disease in some countries, especially in Brazil, where 40 000 new cases are diagnosed every year (Duppre et al., 2012). Since 1965, thalidomide has been used for the treatment of ENL (Oliveira et al., 1999). Although there is a strict legislation for the prescription and use of thalidomide in Brazil (Resolution RDC N1-11 March 22, 2011. National Health Surveil- lance Agency of Brazil (ANVISA), cases of thalidomide embryopathy have continued to be reported over the decades (Castilla et al., 1996; Schuler-Faccini et al., 2007). Here, we present two new cases of thalidomide embryo- pathy identified in 2011 and review the major clinical findings that can aid the identification of the embryo- Original article 59 0962-8827  c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MCD.0b013e32835ffc58 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.