Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta-CAGexp from parent-offspring pairs, and delta-CAGexp between siblings were obtained. One hundred and fifty-nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p < 0.001). Median instability was larger among paternal than maternal transmissions, and instabilities correlated with anticipation (r = 0.38; p = 0.001). Age of the parent correlated to delta-CAGexp among 115 direct parent-offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta-CAGexp between 269 siblings correlated with their delta-of-age (ρ = 0.27, p < 0.0001). SCA3/MJD was associated with a segregation distortion favoring the expanded allele in our cohort. Instability of expansion during meiosis was weakly influenced by the age of the transmitting parent at the time of conception.

Abstract. This study aimed to investigate the role of maternal polymorphisms, as well as their risk genotypes combinations of MTR A2756G, MTRR A66G, CBS 844ins68, and RFC A80G, involved in folate/homocysteine metabolism, as possible risk factors for Down syndrome (DS) in Southern Brazil. A case-control study was conducted with 239 mothers of DS children and 197 control mothers. The investigation of polymorphisms was performed by PCR and PCR-RFLP. The distribution of genotypic variants was similar in both groups when they were analyzed separately. An investigation of combined risk genotypes showed that the risk of having a DS child for one, two or three risk genotypes was 6.23, 6.96 and 5.84 (95%CI 1.48-26.26; 1.69-28.66; 1.37-24.86), respectively. The combined MTRR 66G and MTHFR 677T alleles were significantly more common among mothers of children with DS than among control mothers (OR 1.55; IC 95% 1.03-2.35). The results show that individual polymorphisms studied in this work are not associated with DS; however, the effects of the combined risk genotypes among MTR, MTRR, CBS and RFC genes are considered maternal risk factors for DS offspring in our population.

The objective of the present study was to evaluate and quantify fetal risks involved in the administration of cancer chemotherapy during gestation, as well as to assess the long-term effects on the exposed children. In this retrospective, cohort study, we reviewed the records of women aged 15 to 45 years with a diagnosis of malignancy or benign tumors with malignant behavior at three reference services in the State of Rio Grande do Sul, Brazil, from 1990 to 1997. All patients with a diagnosis of pregnancy at any time during the course of the disease were selected, regardless of whether or not they received specific medication. Fetal outcomes of 14 pregnancies with chemotherapy exposure were compared to that of 15 control pregnancies in which these drugs were not used. Long-term follow-up of the exposed children was carried out. Fisher's exact test was used to compare the groups. Continuous variables were compared by the Wilcoxon-Mann-Whitney test. We found an increased rate of prematurity (6/8 vs 2/10; RR: 3.75; CI: 1.02-13.8; P = 0.03) in the exposed group. There was a trend to an increased fetal death rate (4/12 vs 0/10; P = 0.07) in the group exposed to chemotherapy. No malformations were detected in any child, which can be related to our small sample size as well as to the fact that most exposures occurred after the first trimester of pregnancy. Other larger, controlled studies are needed to establish the actual risk related to cancer chemotherapy during pregnancy.

Resumo ObjetivoAvaliar a relação entre o impacto ambiental decorrente da extração de carvão e sua repercussão na saúde reprodutiva de uma população, residente em pequenas cidades do Sul do Brasil, pela observação da freqüência de defeitos congênitos nos recém-nascidos. Métodos Foram monitoradas as freqüências de oito defeitos congênitos em 10.391 nascidos vivos, ocorridos no período de janeiro de 1985 a dezembro de 1995 em um hospital localizado no município de São Jerônimo, RS. Destes, foram selecionados oito maiores defeitos congênitos, e a análise de suas prevalências ao nascimento visou reduzir os possíveis erros-diagnósticos. As taxas de defeitos congênitos foram comparadas às de outros hospitais geograficamente próximos e às fornecidas pelo Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC) para a América Latina. Resultados/ConclusõesAs freqüências observadas não diferiram das encontradas em hospitais regionais e no ECLAMC. O pequeno número de crianças avaliadas mostra apenas algumas tendências, concluindo serem necessários outros estudos mais profundos. Abstract Objective To assess the relationship between the environmental impact of coal mining and its effects in the reproductive health of populations living in small towns of Southern Brazil by studying the frequency of birth defects in newborns. Methods The assessment of potential reproductive hazards in the population was based on an evaluation of hospital records of 10,391 newborns within a 10-year-period (from 1985 to 1995). Eight major birth defects were selected and their frequencies at birth was analyzed and compared to observed frequencies registered by the Latin American Study of Congenital Malformation (ECLAMC). Results/ConclusionsThe results show no increase in the frequencies of the birth defects studied, and rule out the existence of an increased teratogenic risk in this region. It's noteworthy that the small number of children evaluated allows identifying tendencies that can only be confirmed in larger population studies.

Congenital absence of skin (CAS) is a clinical sign associated with the main types of epidermolysis bullosa (EB). Very few studies have investigated the genetic background that may influence the occurrence of this condition. Our objective was to investigate genotype-phenotype correlations on EB with CAS through a literature revision on the pathogenic variants previously reported. A total of 171 cases (49 EB simplex, EBS; 23 junctional EB, JEB; and 99 dystrophic EB, DEB), associated with 132 pathogenic variants in eight genes, were included in the genotype-phenotype analysis. In EBS, CAS showed to be a recurrent clinical sign in EBS with pyloric atresia (PA) and EBS associated with kelch-like protein 24; CAS was also described in patients with keratins 5/14 alterations, particularly involving severe phenotypes. In JEB, this is a common clinical sign in JEB with PA associated with premature termination codon variants and/or amino acid substitutions located in the extracellular domain of integrin α6β4 genes. In DEB with CAS, missense variants occurring close to non-collagenous interruptions of the triple-helix domain of collagen VII appear to influence this condition. This study is the largest review of patients with EB and CAS and expands the spectrum of known variants on this phenomenon.

Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.

We describe a boy presenting with macrosomy, body asymmetry, cutis marmorata and tall stature who developed a retinoblastoma. Although he does not have macrocephaly, his clinical picture is compatible with the diagnosis of Macrocephaly-cutis marmorata telangiectatica congenita syndrome (M-CMTC). Interestingly, retinoblastoma is not generally associated with overgrowth syndromes, and its occurrence in this patient suggests that M-CMTC is also a tumour-prone syndrome.

Objective: Although the classic features of fetal alcohol syndrome have been recognized since 1968, research on alcohol teratogenesis has only recently demonstrated that the brain is the organ in the body most vulnerable to the effects of prenatal alcohol exposure. In this present article, we reviewed the literature focusing mainly on behavioral disturbances related to prenatal ethanol exposure. Sources:We performed a PubMed search on the literature published between 1968 and 2006 using the terms ethanol, pregnancy and behavior. We limited our search to studies on humans. Summary of the findings:The data presented in this review suggested that youths with fetal alcohol spectrum disorder are at risk of disruptive social behavior, among other neurobehavioral abnormalities. Conclusions:Although it is still impossible to completely separate brain teratogenesis secondary to alcohol exposure from environmental postnatal influences as the definite cause for these outcomes, the pediatrician should be encouraged to early diagnose children affected by fetal alcohol syndrome and fetal alcohol spectrum disorder. This provides proper management and care and avoids long-term consequences on their behavior, besides ensuring better and productive school and social adaptation.J Pediatr (Rio J). 2008;84(4 Suppl):S76-79: Fetal alcohol syndrome, ethanol, alcohol, behavior, pregnancy, teratogenesis.