Introduction to the special issue on Clinical Genetics in Latin America

In this special issue of the American Journal of Medical Genetics Part C, Seminars in Medical Genetics, we show the diversity of Clinical Genetics in the Latin American region. A collection of 19 manuscripts with authors from 55 genetic programs across 11 countries demonstrates strong collaborations and partnerships across the region. There are also collaborations with 16 centers in the United States with an emphasis on efforts to provide access to genetic services, telemedicine, education, training, and scientific collaborations. This collection also contains molecular data, including exomes from over 1,000 individuals in the Latin American region. There are tremendous efforts in population screening, healthcare outcomes, epidemiological surveillance, and examples of network development to maximize utilization of genetic information, provide diagnosis, and manage patients with rare diseases. Disease-specific cohorts such as RASopathies, skeletal dysplasia, earlyonset Alzheimer's disease, orofacial clefts, craniofacial microsomia, hypertrichosis, and many others are highlighted in this special issue. This special will serve as a reference for the breadth of innovative work being developed to provide genetics care in Latin America. Large genomic studies are currently underway in the region. First, a reinterpretation of variants of uncertain significance in a cohort of 341 individuals with neurogenetic disorders from Buenos Aires and Cincinnati during follow up showed a 30% reclassification to pathogenic variants (Salinas et al., 2020). In another study using exome analysis in 500 individuals from Brazil (Quaio et al., 2020), the authors provided a high diagnostic yield and therapeutic and management interventions tailored to specific diagnosis. In this study, there was a 7.4% rate of secondary findings using the ACMG reporting recommendations. Several examples of healthcare outcomes and population screenings studies are presented in this special, and these groups' efforts are important to identify management needs and allocate better resources to deliver care in Latin America. Brazil's Craniofacial Project analyzed healthcare outcomes of 1,322 individuals with orofacial clefts across states (Gil-da-Silva-Lopes et al., 2020). The majority of individuals had nonsyndromic oral clefts (n = 1,025), and chromosomal abnormalities were the most common syndromic etiology (n = 93). This highlights the need to facilitate access to testing and identify needs in this population. Genomic imbalances in 54 Brazilian individuals with craniofacial microsomia identified chromosomal abnormalities in 8 individuals, and 22q11.2 deletion syndrome was the most common etiology (Spineli-Silva et al., 2020). Congenital heart disease was found in the majority of individuals with pathogenic deletions. A large cohort of individuals with autosomal dominant early-onset Alzheimer's disease due to a founder PSEN1 pathogenic variant c.1292C>A (p.A431E) was characterized in Mexico (Dumois-Petersen et al., 2020). This study presents valuable phenotypic and genotype information to help develop public health measurements to identify at-risk individuals and population screening based on risk stratification and appropriate genetic counseling. A comprehensive analysis of genetic studies to detect carriers of hemophilia A and B was performed in the Mexican population (González-Ramos et al., 2020). This study presents data from 558 independent families with hemophilia A (n = 1,389) and 74 families with hemophilia B (n = 320). Detailed molecular, linkage, inversion, and X-inactivation studies were performed to increase diagnostic detection and provide appropriate counseling in the Mexican population. The Latin American Network for Congenital Malformation Surveillance, ReLAMC, aims to increase epidemiological surveillance in Latin America (Orioli et al., 2020). This network includes five national and six regional registries from the following countries: Argentina, Brazil, Chile, Costa Rica, Paraguay, Colombia, Nicaragua, and Mexico. A total of 101,749 newborns with malformations are included in the database from a total of over 9 million births. The ReLAMC database contains information about rates of microcephaly, neural tube defects, congenital heart disease, cleft lip and palate, and many others across the different regions. These efforts will allow us to monitor changes in incidence and help develop public policies in Latin American countries. Tertiary centers across the Latin American region have developed expertise across many different disorders and provided innovative care by developing care networks. A center in Brazil provides an 18-year experience of the diagnosis, follow up, and management of 242 individuals with RASopathies (Bertola et al., 2020). Noonan syndrome (n = 185) was the most common RASopathy in this cohort, followed by cardiofaciocutaneous syndrome (n = 23). This manuscript presents genotype–phenotype correlations, common and atypical presentations in this population. Another recent experience from a new program for Noonan syndrome in the southwest region of Colombia describes molecular and clinical data from 26 individuals (Lores et al., 2020). The incidence of cardiomyopathy was low in this population compared to other cohorts. These efforts highlight the importance of creating referral centers for the management of rare diseases. Skeletal dysplasias are a particular group of genetic diseases requiring specific expertise for the diagnosis. In Latin America, although DOI: 10.1002/ajmg.c. 31875