Holoprosencephaly (HPE) is genetically heterogeneous with four genes, SIX3, SHH, TGIF, and ZIC2 that have been identified to date and that are altered in 12% of patients. To analyze this prevalence in a South American population-based sample (57 HPE cases in 244,511 live and still births or 1 in 4300), we performed a mutational study of these genes in 30 unrelated children (26 newborns and 4 non-newborns) with HPE being ascertained by ECLAMC (Latin American Collaborative Study of Congenital Malformations). We identified three novel mutations: two were missense mutations of the SHH gene (Cys183-->Phe; His140-->Pro); the third mutation was a 2-bp deletion in the zinc-finger region of the ZIC2 gene. These molecular results explained 8% (2/26 newborn samples) of the HPE cases in this South American population-based sample, a proportion similar to our previously published data from a collection of cases.

Thalidomide, mainly used for the treatment of leprosy, is a current teratogen in South America, and it is reasonable to assume that at present this situation is affecting many births in underdeveloped countries. Moreover, the potential re‐marketing of thalidomide for the treatment of a large variety of diseases may extend the problem to the developed world. When the drug is available, the control of its intake during early pregnancy is very difficult since most pregnancies are unintended. The ongoing occurrence of thalidomide embryopathy cases went undetected by the ECLAMC, due to several factors: (1) low populational coverage through this monitoring system; (2) pre‐existence of the teratogen with its effects present in both baseline (expected) and monitored (observed) materials; and (3) lack of a defined phenotype to be monitored. Thus, if thalidomide re‐enters the market throughout the world, due to the wide range of new applications, occurrence of phocomelia alone might not be sufficient to detect its effects. By a case‐reference approach, the ECLAMC registered 34 thalidomide embryopathy cases born in South America after 1965 whose birthplaces correspond to endemic areas for leprosy. Phocomelia was found in five of eleven fully described cases. Thus, phocomelia alone is neither specific nor sufficient to serve as a suitable phenotype to survey the teratogenic effects of thalidomide. Therefore, a thalidomide‐like phenotype, defined as any bilateral upper and/or lower limb reduction defect of the preaxial and/or phocomelia types, should be included in the routine surveillance of birth defects in all programmes. Teratology 54:273–277, 1996. © 1997 Wiley‐Liss, Inc.

artículo de investigación rev Med chile 2010; 138: 567-572 38 Años de vigilancia epidemiológica de labio leporino y paladar hendido en la maternidad Evolution of prevalence rates of orofacial clefts in a maternity of a Chilean clinical hospital Background: Orofacial clefts are common and have a great medical and social importance. The Latin American Study of Congenital Malformations (ECLAMC), has maintained an epidemiological surveillance of congenital malformations since 1969, allowing the evaluation of trends in the prevalence of malformations. Aim: To evaluate the evolution curve of prevalence rates of orofacial clefts from 1971 to 2008. Material and Methods: All cases of orofacial clefts, occurring in newborns from the maternity of a university hospital from January 2000 to December 2008, were recorded as part of the ECLAMC. Historical information about the rates of the malformation between 1971 and 1999, was obtained from previous manuscripts of the authors. Results: In the study period, 15,635 children were born and 46 had cleft lip-palate (3‰). This rate is significantly higher than those observed previously, that fluctuated between 1.5 and 1.7‰. The prevalence rates of cleft lip remained stable from 1971 to 1999 and suffered a brisk and significant rise in the period [2000][2001][2002][2003][2004][2005][2006][2007][2008] When the period is analyzed year by year, the increase in rates is observed in the last two years. The rates of cleft palate suffered a slight non significant rise until 2000. Conclusions:The increased rates of cleft lip palate observed in the last two years of the observation period may be a random result and should be monitored in the future. (Rev Med Chile 2010; 138: 567-572).

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The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA) haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers.