Patrícia Trevisan

45,X/46,XY mosaicism: report on 14 patients from a Brazilian hospital. A retrospective study

CONTEXT AND OBJECTIVE 45,X/46,XY mosaicism, or mixed gonadal dysgenesis, is considered to be a rare disorder of sex development. The aim of our study was to investigate the clinical and cytogenetic characteristics of patients with this mosaicism. DESIGN AND SETTING A retrospective study in a referral hospital in southern Brazil. METHODS Our sample consisted of patients diagnosed at the clinical genetics service of a referral hospital in southern Brazil, from 1975 to 2012. Clinical and cytogenetic data were collected from the medical records. RESULTS Fourteen patients were included in the sample, with ages at the first evaluation ranging from 2 days to 38 years. Nine of them had female sex of rearing and five, male. Regarding the external genitalia, most were ambiguous (n = 10). One patient presented male phenotype and was treated for a history of azoospermia, while three patients presented female phenotype, of whom two had findings of Turner syndrome and one presented secondary amenorrhea alone. Some findings of Turner syndrome were observed even among patients with ambiguous genitalia. None presented gonadal malignancy. One patient underwent surgical correction for genital ambiguity and subsequent exchange of sex of rearing. Regarding cytogenetics, we did not observe any direct correlation between percentages of cell lines and phenotype. CONCLUSIONS 45,X/46,XY mosaicism can present with a wide variety of phenotypes resulting from the involvement of different aspects of the individual. All these observations have important implications for early recognition of these patients and their appropriate management.

Evaluation of genotoxic effects of benzene and its derivatives in workers of gas stations

The search for reliable biomarkers of human exposure to benzene and its derivatives is still subject of research. Many of the proposed biomarkers have limitations ranging from the low sensitivity to the wide variability of results. Thus, the aim of our study was to assess the frequencies of chromosomal abnormalities (CA) and sister chromatid exchanges (SCE) in workers of gas stations, with (cases, n = 19) and without (local controls, n = 6) risk of exposure to benzene and its derivatives, comparing them with the results from the general population (external controls, n = 38). The blood dosages of benzene, toluene, and xylenes were measured in all participants. Blood solvent levels were compared with the findings obtained in cytogenetic evaluation and a research protocol which included data of the workplace, lifestyle, and health of the individuals. We did not detect the presence of benzene and its derivatives and did not find chromosomal damage that may be associated with the gas station activity in cases. Moreover, although we found an association of increased SCE and the working time in the local controls, the values found for SCE are within normal limits. Thus, our evaluation of SCE and CA reflected the levels of benzene and its derivatives observed in the blood. We believe, therefore, that SCE and CA may actually constitute possible tests for the evaluation of these exposures. However, we believe that further studies, including individuals at risk, are important to confirm this assertion.

Gómez-López-Hernández Syndrome in a Child Born to Consanguineous Parents: New Evidence for an Autosomal-Recessive Pattern of Inheritance?

BACKGROUND Gómez-López-Hernández syndrome is a rare genetic disease characterized by scalp alopecia with trigeminal anesthesia, brachycephaly or turribrachycephaly, midface retrusion, and rhombencephalosynapsis. We report the second case with this condition who presented with consanguineous parents. PATIENT This boy was evaluated shortly after birth because of suspected craniosynostosis. He was the only son of healthy, consanguineous parents (his maternal grandmother and his paternal great-grandfather were siblings). His examination was notable for turribrachycephaly, prominent forehead, bilateral parietotemporal alopecia, midfacial retrusion, anteverted nostrils, micrognathia, low-set and posteriorly rotated ears, and short neck with redundant skin. Radiographs and tridimensional computed tomography scan of skull revealed lambdoid craniosynostosis. Brain magnetic resonance imaging revealed complete rhombencephalosynapsis, aqueductal stenosis, fused colliculi, abnormal superior cerebellar penducle, mild ventriculomegaly, and dysgenesis of the corpus callosum. CONCLUSIONS Since its first description, 34 patients with this condition have been reported. The etiology of Gómez-López-Hernández syndrome is unknown. However, it is noteworthy that the patient in this report presented with a family history of consanguinity because this finding reinforces the possibility of an autosomal-recessive inheritance for this condition.

Clinical and cytogenetic features of a Brazilian sample of patients with phenotype of oculo-auriculo-vertebral spectrum: a cross-sectional study

CONTEXT AND OBJECTIVE Oculo-auriculo-vertebral spectrum (OAVS) is considered to be a defect of embryogenesis involving structures originating from the first branchial arches. Our objective was to describe the clinical and cytogenetic findings from a sample of patients with the phenotype of OAVS. DESIGN AND SETTING Cross-sectional study in a referral hospital in southern Brazil. METHODS The sample consisted of 23 patients who presented clinical findings in at least two of these four areas: orocraniofacial, ocular, auricular and vertebral. The patients underwent a clinical protocol and cytogenetic evaluation through high-resolution karyotyping, fluorescence in situ hybridization for 5p and 22q11 microdeletions and investigation of chromosomal instability for Fanconi anemia. RESULTS Cytogenetic abnormalities were observed in three cases (13%) and consisted of: 47,XX,+mar; mos 47,XX,+mar/46,XX; and 46,XX,t(6;10)(q13; q24). We observed cases of OAVS with histories of gestational exposition to fluoxetine, retinoic acid and crack. One of our patients was a discordant monozygotic twin who had shown asymmetrical growth restriction during pregnancy. Our patients with OAVS were characterized by a broad clinical spectrum and some presented atypical findings such as lower-limb reduction defect and a tumor in the right arm, suggestive of hemangioma/lymphangioma. CONCLUSIONS We found a wide range of clinical characteristics among the patients with OAVS. Different chromosomal abnormalities and gestational expositions were also observed. Thus, our findings highlight the heterogeneity of the etiology of OAVS and the importance of these factors in the clinical and cytogenetic evaluation of these patients.

Congenital heart disease and chromossomopathies detected by the karyotype

Objective: To review the relationship between congenital heart defects and chromosomal abnormalities detected by the karyotype. Data sources: Scientific articles were searched in MEDLINE database, using the descriptors “karyotype” OR “chromosomal” OR “chromosome” AND “heart defects, congenital”. The research was limited to articles published in English from 1980 on. Data synthesis: Congenital heart disease is characterized by an etiologically heterogeneous and not well understood group of lesions. Several researchers have evaluated the presence of chromosomal abnormalities detected by the karyotype in patients with congenital heart disease. However, most of the articles were retrospective studies developed in Europe and only some of the studied patients had a karyotype exam. In this review, only one study was conducted

Síndrome de deleção 22q11 e cardiopatias congênitas complexas

OBJECTIVE: Investigate the frequency of 22q11 deletion syndrome among patients with complex congenital heart disease. METHODS: A prospective and consecutive cohort of patients with complex heart defects was evaluated in their first hospitalization at a cardiac intensive care unit of a pediatric hospital. For each patient a protocol of demographic and clinical evaluation was filled. High resolution karyotype and 22q11 microdeletion by fluorescence in situ hybridization was investigated. The heart defects were classified by a cardiologist of the study. RESULTS: The cohort comprised 66 patients. Karyotypic anomalies were observed in 5 patients (7.6%), however none of those was the 22q11 deletion. Evaluation by means of FISH was successful in 65 patients and 22q11 microdeletion was identified in 2 (3.1%). Of the 66 patients with complex defects, 52 were carriers of conotruncal malformations and in 51 the 22q11 microdeletion analysis by FISH was successful. Both 22q11 microdeletion carriers belonged to this group, representing a frequency of 3.9%. They presented tetralogy of Fallot. CONCLUSION: 22q11DS is a frequent abnormality among patients with complex and conotruncal heart defects. Variations of the 22q11DS frequency among studies seem to be mainly associated to criteria for patient selection and specific characteristics of the population in analysis.

Chromosomal abnormalities in patients with congenital heart disease.

Background Chromosomal abnormalities (CAs) are an important cause of congenital heart disease (CHD). Objective Determine the frequency, types and clinical characteristics of CAs identified in a sample of prospective and consecutive patients with CHD. Method Our sample consisted of patients with CHD evaluated during their first hospitalization in a cardiac intensive care unit of a pediatric referral hospital in Southern Brazil. All patients underwent clinical and cytogenetic assessment through high-resolution karyotype. CHDs were classified according to Botto et al. Chi-square, Fisher exact test and odds ratio were used in the statistical analysis (p < 0.05). Results Our sample consisted of 298 patients, 53.4% males, with age ranging from 1 day to 14 years. CAs were observed in 50 patients (16.8%), and 49 of them were syndromic. As for the CAs, 44 (88%) were numeric (40 patients with +21, 2 with +18, 1 with triple X and one with 45,X) and 6 (12%) structural [2 patients with der(14,21), +21, 1 with i(21q), 1 with dup(17p), 1 with del(6p) and 1 with add(18p)]. The group of CHDs more often associated with CAs was atrioventricular septal defect. Conclusions CAs detected through karyotyping are frequent in patients with CHD. Thus, professionals, especially those working in Pediatric Cardiology Services, must be aware of the implications that performing the karyotype can bring to the diagnosis, treatment and prognosis and for genetic counseling of patients and families.

22q11.2 deletion syndrome and complex congenital heart defects

OBJECTIVE Investigate the frequency of 22q11 deletion syndrome among patients with complex congenital heart disease. METHODS A prospective and consecutive cohort of patients with complex heart defects was evaluated in their first hospitalization at a cardiac intensive care unit of a pediatric hospital. For each patient a protocol of demographic and clinical evaluation was filled. High resolution karyotype and 22q11 microdeletion by fluorescence in situ hybridization was investigated. The heart defects were classified by a cardiologist of the study. RESULTS The cohort comprised 66 patients. Karyotypic anomalies were observed in 5 patients (7.6%), however none of those was the 22q11 deletion. Evaluation by means of FISH was successful in 65 patients and 22q11 microdeletion was identified in 2 (3.1%). Of the 66 patients with complex defects, 52 were carriers of conotruncal malformations and in 51 the 22q11 microdeletion analysis by FISH was successful. Both 22q11 microdeletion carriers belonged to this group, representing a frequency of 3.9%. They presented tetralogy of Fallot. CONCLUSION 22q11DS is a frequent abnormality among patients with complex and conotruncal heart defects. Variations of the 22q11DS frequency among studies seem to be mainly associated to criteria for patient selection and specific characteristics of the population in analysis.

Macrothrombocytopenia as diagnosis predictor of 22q11 deletion syndrome among patients with congenital heart defects

Macrothrombocytopenia as Diagnosis Predictor of 22q11 Deletion Syndrome Among Patients with Congenital Heart Defects Patrı́cia Trevisan, Sı́lvia Barbosa, Graziela Sperotto, Caroline Costi, Reinaldo L. de Omena Filho, Alessandra P. da Silva, Marileila Varella-Garcia, Marilu Fiegenbaum, Rafael F. M. Rosa, and Paulo R. G. Zen* Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Cytogenetics Laboratory, UFCSPA, Porto Alegre, RS, Brazil Graduation in Medicine, Universidade Luterana do Brasil (ULBRA), Porto Alegre, RS, Brazil Clinical Genetics, UFCSPA and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, RS, Brazil School of Medicine, Division of Medical Oncology, University of Colorado Denver, Denver, Colorado Human Genetics, UFCSPA, Porto Alegre, RS, Brazil Clinical Genetics, Hospital Materno Infantil Presidente Vargas (HMIPV), Porto Alegre, RS, Brazil

Cytogenetic profile of patients with Down syndrome in southern Brazil.

The aim of our study was to investigate the cytogenetic findings of patients with Down syndrome who were diagnosed by a clinical genetics service in southern Brazil between 1975 and 2008. All karyotyping was performed in the same labo-ratory, using the G-bands by trypsin using Giemsa (GTG) technique. A mean of 22 cells per case were analyzed (range: 5 – 80).Our sample comprised 644 patients (364 males and 280 females). Full trisomy of chromo-some 21 was the predominant alteration observed in 598 of these patients (92.9%). Chromosomal abnormalities of structural type were observed in 26 patients (4%). These were composed of Robertsonian translocations involving chromosome 21 and chromosomes 14 (n = 12), 21 (n = 10), 15 (n = 1) and 22 (n = 1). In addition, two cases showed a reciprocal translocation, one of them involving chromosomes 21 and 5 and another with a complex translocation involv -ing chromosomes 5, 21 and 22. Among the patients with structural chromosomal abnormali-ties, karyotyping analysis on the parents was performed in relation to 11 patients. Structurally balanced alterations were detected in five of them (45.5%). Mosaicism was identified in 20 patients (3.1%) and usually involved two cell lines: one normal and one with trisomy 21 (n = 15). However, two patients (10%) presented mosaicism involving three cell lines. Five cases (25%) showed a cell line with double aneuploidy, and four of them involved chromosomes 9, 14, 21 and X, respectively. The fifth patient presented an additional marker chromosome. Six patients (30%) among the 20 had mosaicism for trisomy 21 that was lower than 10%. The mean number of cells analyzed in these cases was 42 (the maximum was 80 cells; range: 15 – 80).In our review of the literature, using the PubMed, SciELO and Lilacs databases, we did not identify any studies that evaluated the cytogenetic profile of patients with Down syndrome in Latin America. The frequencies of the different changes to chromosome 21 observed in our study were consistent with those described in the literature.