Evaluation of the real risk of development of gonadal tumors in TS patients with Y-derivative sequences in their chromosomal constitution may require a specific histopathological study, such as immunohistochemistry with OCT4.

We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpoints--unique for each patient--could be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder.

Considering the prevalence of 22q11.2 deletion syndrome (22q11.2 DS) of around 1:4,000 and of palatal abnormalities in 70 % of the cases of 22q11.2 DS and taking into account the Brazilian health system and its current situation of medical genetic services, this study aims to contribute to establish strategies for genetic diagnosis. The access to genetic testing at 11 services was investigated and samples from 100 patients with palatal abnormalities and suspicion of 22q11.2 DS were sent to a reference center. Laboratorial techniques included karyotyping, fluorescence in situ hybridization (FISH), and multiplex ligation-dependent probe amplification. Costs were also calculated. Disparities among centers for genetic diagnosis were evident, with remarkable regional differences. Some of the obstacles encountered were difficulties for families to show up for medical appointments, complementary evaluations, and for the clinics to send the samples to the reference center. A conclusive diagnosis was reached for 38 % of patients. Combination of karyotyping and FISH had better laboratorial cost-effectiveness. These results might represent the reality for the investigation of other genetic conditions. Clinical and laboratorial approaches herein presented could be adapted for use under different genetic conditions in the Brazilian health system, which has relatively limited financial and human resources. Suggestions for the rational implementation of genetic testing in developing countries are presented.

The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, with a highly variable phenotype. This chromosomal region contains low copy repeat (LCR) sequences that mediate non-allelic homologous recombination which predispose to copy number abnormalities at this locus. This article describes three patients investigated for suspicion of 22q11.2DS presenting atypical copy number abnormalities overlapping or not with the common ∼3 Mb deletion. They were investigated by G-banding karyotype, Multiplex-ligation dependent probe amplification (MLPA) and array Genomic Hibridization (aGH). Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. Atypical chromosomal abnormalities were detected: 3.6 Mb deletion at 22q11.21-q11.23 between LCRs B-F in patient 1 and approximately 1.5 Mb deletion at 22q11.21-q11.22 between LCRs D-E in patients 2 and 3. The breakpoints detected in patient 1 have not been previously described. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 region and corroborates the idea that genetic modifiers contribute to the phenotypic variability observed in proximal and distal 22q11.2 deletion syndromes.

These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.

Objective : To describe demographic and clinical-genetic characteristics of patients from a poor area of Brazil and to share experience on how the local genetic unit has addressed their major health needs. Design : Descriptive cohort. Setting : A clinical-genetic unit, a cytogenetics unit, and a regional cleft team located in the northeast and southeast of Brazil. Participants : A total of 133 individuals with orofacial clefts who attended the surgical call of a nongovernmental organization. From this group, 125, 77, and 13 patients completed phases 1, 2, and 3, respectively. Methods : Phase 1 comprised a description of demographic characteristics recorded through interviews. Phase 2 included a clinical-genetic evaluation using a pretested form, as well as cytogenetic analyses of selected patients. Phase 3 comprised collaborative action to address major health needs of patients without primary surgery. The Fisher test was used for statistics with p value < .05. Results : A majority of patients were rural residents with isolated cleft lip with cleft palate. Ages ranged between 0 and 30 years. Fifty percent had never undergone surgery; whereas, 100% had never attended a genetic evaluation. Isolated cleft was diagnosed in 77.9%, syndromes in 14.3%, and multiple congenital abnormalities in 7.8%. Positive familial history of clefts occurred in 28%; whereas, parental consanguinity was present in 7.8% cases. A total of 23 individuals without cleft surgery were registered for multidisciplinary treatment. Conclusions : Findings revealed high levels of unmet medical needs and provided an evidence base for health care planning. Collaborative action was crucial and might be applied to other regions in Brazil.

We report on a boy presenting submucous cleft palate, hydronephrosis, ventriculoseptal defect, aniridia, and developmental delay. Additional material on 11p13 was cytogenetically visible and array analyses identified a duplicated segment on 15q25-26 chromosome region; further, array analyses revealed a small deletion (49 kb) at 11p13 region involving the ELP4 gene and a duplication at 8p23.1. Results were confirmed with both molecular and molecular cytogenetics techniques. Possibilities for etiological basis of clinical phenotype are discussed.

Short stature seen in this series confirms a previous study describing this feature in a German population, which would suggest it as an intrinsic feature in Williams-Beuren syndrome. In addition, skinfold thickness measures have not been previously performed in this syndrome and detected abnormalities in fat stores in this sample. Considering this method a fast and low-cost way to evaluate body composition, similar studies could be performed in other populations in order to better characterize this issue. Morbidity related with this genetics condition and information for clinical investigation and clinical follow-up are also discussed.