Although LSDs are rare disorders as a group, they should be considered as a possible cause of NIHF, even in the absence of consanguinity or of a previous family history. By excluding the more frequent causes of NIHF, an LSD investigation assists in clarifying the etiology of many hydropic cases, making more appropriate genetic counseling for parents possible.

ResumoOBJETIVO: Descrever a prevalência das malformações encontradas nos fetos com trissomia dos cromossomos 13, 18 e 21, identificando as mais frequentes em cada condição. MÉTODOS: Estudo transversal retrospectivo, com análise dos casos de trissomias dos cromossomos 13, 18 e 21 que foram diagnosticados pelo cariótipo fetal obtido por amniocentese/cordocentese, entre outubro de 1994 e maio de 2014, em um Hospital de Ensino da região Sul do Brasil. Foram descritas as malformações identificadas no exame ultrassonográfico morfológico e, posteriormente, confirmadas em exames do recém-nascido e/ou por necropsia fetal. Os resultados foram analisados por meio do teste de Fisher e da análise de variância (ANOVA). O nível de significância empregado foi 5% (p=0,05). RESULTADOS: Em 840 exames realizados, foram diagnosticados 69 casos de trissomias; nove deles foram excluídos por desfecho ocorrido fora do Hospital de Clínicas de Porto Alegre ou prontuário incompleto, restando 60 casos (nove de trissomia do cromossomo 13, 26 do cromossomo 18 e 25 do cromossomo 21). As cardiopatias ocorreram, na maioria dos casos, nos três grupos; a comunicação interventricular foi mais prevalente, em 66,7% do grupo da trissomia 13. As anomalias gastrintestinais aconteceram mais no grupo da trissomia 18, principalmente a onfalocele (38,5%; p<0,01). As anomalias geniturinárias foram significativamente mais frequentes no grupo da trissomia 13 (pielectasia com 55,6% -p<0,01; genitália ambígua com 33,3% -p=0,01). Defeitos do sistema nervoso central foram identificados em todos os casos de trissomia 13. Fendas faciais foram mais prevalentes dentre os fetos com trissomia 13 (66,7%; p<0,01). Malformações nas mãos e nos pés tiveram diferenças estatísticas entre os grupos de trissomia. Os defeitos nas mãos ocorreram em 50% dos casos de trissomia 18 e em 44,4% dos casos de 13 (p<0,01); pé torto congênito foi mais comum no grupo da trissomia 18, descrito em 46,2% dos fetos (p<0,01). As malformações foram identificadas em 50,9; 27,3 e 21,7% dos casos de trissomias 18, 13 e 21, respectivamente. CONCLUSÃO: Muitas malformações identificadas na ultrassonografia são sugestivas de trissomias e mostram-se ferramentas importantes para o diagnóstico etiológico e aconselhamento genético pré-natal e pré-concepcional. Abstract PURPOSE:To describe the prevalence of malformations found in fetuses with trisomy of chromosomes 13, 18 and 21 by identifying the most frequent within each condition. METHODS: A retrospective cross-sectional study with the analysis of trisomy cases of chromosomes 13, 18 and 21 diagnosed through fetal karyotype obtained by amniocentesis/ cordocentesis, between October 1994 and May 2014, at a Teaching Hospital in Brazil Southern Region. Malformations identified through morphological ultrasonography were described and, subsequently, confirmed in newborn examinations and/or fetal autopsy. The results were analyzed using Fisher's test and analysis of variance (ANOVA), with a 5% level of significance (p=0.05). RESULTS: Sixty-nine cases of trisomy we...

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Trisomy 18 (T18) and trisomy 13 (T13) are polymalformative syndromes associated with a high rate of spontaneous abortions, intrauterine death, and short postnatal life. This study describes the overall outcome in a country where the therapeutic interruption of pregnancy is not available. The medical records of women with prenatal diagnosis of full trisomy of T13 or T18 between October 1994 and October 2017 were analyzed in order to describe their natural outcomes. Thirteen cases of T13 and 29 cases of T18 were included. The miscarriage rate was 9% for T18 and no cases for T13. Intrauterine fetal death occurred in 46% and 52% of cases for T13 and T18, respectively. The rate of live births for T13 was 54%, and the median survival was one day (95% CI -33.55 - 90.40) and 71% died in the first 24 hours of life. The rate of live births for T18 was 37% and the median survival was two days (95% CI -1.89 - 13.17); 90% of the affected babies died within first week of life. For the affected babies reaching the first year of life and for those who lived longer, multiple invasive and expensive procedures were required, without success in prolonging life beyond 180 days. This large series provides information for professionals and women regarding the natural histories of T13 and T18. Results of this study are consistent with those referenced in the literature, emphasizing the need of structured protocols and guidelines aiming early T13 and T18 diagnosis, prenatal care, gestation/parents follow-up, and counseling processes. For those couples with earlier diagnosis, a better follow-up and counseling during the prenatal care lead to the option for a support or palliative management of the newborn. Finally, when the counseling process is appropriate, it becomes easier to take decisions respecting the parent’s autonomy and to look for better outcomes for both, the mother and the fetus.

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RESUMOIntrodução: pacientes em amenorréia primária com disgenesia gonadal têm níveis elevados de gonadotrofinas e necessitam de avaliação cromossômica. O estudo citogenético (cariótipo) pode ser realizado na gônada ou no sangue periférico. Nos casos de amenorréia primária sem sinal de virilização, a necessidade de investigação adicional do cariótipo da gônada não está estabelecida. Objetivo: revisar os cariótipos de gônadas (ovários) de mulheres com amenorréia primária e compará-los com os resultados do cariótipo no sangue periférico, relacionando-os às características fenotípicas das pacientes. ABSTRACT Background: patients with primary amenorrhea and gonadal dysgenesia have higher serum gonadotrophins and should be submitted to chromosome studies. Karyotype studies may be performed in gonadal tissue or peripheral blood however, it is not yet established if cases of primary amenorrhea without signs of virilization need additional investigation of gonadal karyotype. Purpose: to analize the gonadal karyotypes (ovaries) from patients with primary amenorrhea and compare them to their respective peripheral blood karyotypes. Methods: clinical and karyotype data of 12 patients were retrospectively analyzed from January 1997 to December 2003. Results: when the investigation was indicated for primary amenorrhea without signs of virilization, the gonadal and peripheral blood karyotypes were concordant in 8 cases (7 cases 46XX and 1 case 46XY). One patient with virilization signs was the only case of discordant karyotype. Conclusion: the present study suggests that the gonadal karyotype does not bring additional information to peripheral blood karyotype in patients with amenorrhea and no signs of virilization. Although all previous studies had a small number of patients, it seems advisable to investigate the gonadal karyotype in patients with signs of virilization. The cost-benefit analysis could allow cost and stress reduction for patients, family and institutions.

Introduction:During the past few decades, the number of diseases identified to be caused by chromosomal microdeletions has increased quickly, bringing a new and crucial role for cytogenetics on the diagnosis of these conditions. The purpose of this study was to identify and characterize chromosomal microdeletions associated with malformation syndromes and intellectual disability. Methods:We retrospectively evaluated a consecutive series of samples from a cohort of 598 subjects with clinical symptoms of a microdeletion syndrome, including the deletion of chromosomes 4p16.3, 5p15.2, 5q35, 7q11.23, 8q24.12, 15q11.2, 16p13.3, 17p13.3, 17p11.2,2, and 22q11.2, as investigated by fluorescence in situ hybridization (FISH). Array-based comparative genomic hybridization (array-CGH) was performed on 25 samples with microdeletions.Results: A total of 598 samples were evaluated from patients whose clinical phenotypes were most indicative of 22q11.2 deletion syndrome (29.10%), Prader-Willi syndrome (23.41%), Angelman syndrome (16.89%), and Williams-Beuren syndrome (14.72%). In 142 of the samples (23.75%), a chromosomal imbalance associated with phenotypic abnormalities was found. The deletion of 7q11.23 was the most frequent (8.03%), followed by del22q11.2 (5.68%) and del15q11.2 (5%). Conclusion:Our study reinforces the idea that the effort to improve the capacity to perform molecular cytogenetic investigations associated with a qualified clinical evaluation is crucial for the detection and precise characterization of submicroscopic chromosome deletions, bringing benefits to patients, relatives, and genetic counselors. It also contributes to the continuing education of cytogeneticists and to the knowledge of chromosomal rearrangements associated with genomic disorders.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by deficiency of arylsulfatase A (ARSA), leading to an accumulation of sulfatides. Sulfatides have been quantified in urine, dried blood spots (DBS), and tissues of patients with MLD. Newborn screening (NBS) for MLD has already been proposed based on a two-tier approach with the quantification of sulfatides in DBS followed by the quantification of ARSA by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Prenatal screening for MLD is also crucial, and sulfatide quantification in amniotic fluid (AF) can aid diagnosis. The prenatal study was initiated due to a family history of MLD at 19 weeks of gestation. ARSA was quantified in cultured amniocytes. C16:0 sulfatide was quantified by LC-MS/MS in the supernatant of AF. Molecular analysis of the ARSA gene was performed in cultured amniocytes. ARSA was deficient in fetal cells, and C16:0 sulfatides were significantly elevated in comparison to age-matched controls (3-fold higher). Genetic studies identified the c.465+1G>A variant in homozygosis in the ARSA gene. Our study shows that sulfatides can be quantified in the supernatant of AF of MLD fetuses, and it could potentially aid in a faster and more accurate diagnosis of MLD patients.