Prenatal Findings in Postnatal Cases of Disorders of Sex Development: Experience from a Tertiary-Specialized Center in Brazil.

INTRODUCTION AND OBJECTIVE: Prenatal suspicion of disorders/differences of sex development (DSDs) is a relatively new phenomenon. The aim of this study was to review the prenatal findings of DSD cases postnatally diagnosed in our tertiary referral center. METHODS: We evaluated 57 DSD cases with sex ambiguity who had undergone prenatal ultrasound with phenotypic sex assessment and/or cell-free fetal DNA (cffDNA) for genotypic sex assessment. RESULTS: Prenatal cffDNA had been performed in 32 cases, being positive (suggestive of male genotypic sex) in 26 and negative (suggestive of female genotypic sex) in 6. Five with cffDNA negative had a prenatal ultrasound indicating female external genitalia, in turn, in those with cffDNA positive, only two had a prenatal ultrasound indicating male external genitalia. Our postnatal data showed that when external genitalia were female or poorly virilized, prenatal ultrasound indicated female sex, but in cases of higher degree of virilization, ultrasound showed similar rates of male, female, or undetermined sex. Regarding the karyotype, our data showed those with XY karyotype had positive cffDNA, those with XX karyotype had negative cffDNA, and all five with sex chromosome anomalies had positive cffDNA because they were 45,X/46,XY. We suggested an algorithm to investigate these cases during gestation, including evaluation of uterus, fetal growth, and malformations. CONCLUSION: We suggest that the parents should be counseled prenatally by a dedicated multidisciplinary team with experience in DSD management and evaluated as soon as possible after birth.

SOX3 duplication in a boy with 46,XX ovotesticular disorder of sex development and his 46,XX sister with atypical genitalia: Probable germline mosaicism.

Ovotesticular disorders of sex development (OT-DSD) are characterized by ovarian follicles and seminiferous tubules in the same individual, with a wide range of atypical genitalia. We report on two sibs with atypical genitalia and SRY-negative 46,XX DSD, OT-DSD was confirmed only in the boy, while the girl had bilateral ovaries. Chromosome microarray analysis (CMA) showed a 737-kb duplication at Xq27.1 including the entire SOX3 gene in both sibs, which was confirmed by quantitative real time PCR. Also, X chromosome inactivation assay showed random inactivation in both sibs. Whole exome sequencing revealed no pathogenic or likely pathogenic variant. CMA of the parents showed normal results for both, suggesting that germline mosaicism could be the reason of recurrence of this duplication in the siblings. Our results support a pathogenic role of SOX3 overexpression in 46,XX subjects leading to variable DSD phenotypes.

Local strategies to address health needs of individuals with orofacial clefts in alagoas, Brazil.

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.

Anthropometric and body-mass composition suggests an intrinsic feature in Williams-Beuren syndrome / Antropometria e composição de massa corporal sugerem achado intrínseco da síndrome de Williams-Beuren

OBJECTIVE:Although considered a well-known condition, there is only one study describing the body composition among individuals with Williams-Beuren syndrome. The aim was to characterize the nutritional status in Brazilian individuals with this condition. METHODS: Cross-sectional study was designed to evaluate clinical and nutritional data of 17 Brazilian patients. Z-scores for height, weight, body mass index, triceps and subscapular skinfold thickness, arm circumference, arm muscle area, arm fat area were calculated. Wilcoxon's test was used to investigate differences between the z-scores of the anthropometrical measures and zero. RESULTS: Four children were considered stunted and two severely malnourished. The z-score mean value for height was -1.14 ± 1.00 (p-value = 0.004), for weight, -0.67 ± 1.19 (p-value = 0.0443), for arm circumference, -0.94 ± 1.14 (p-value = 0.0222), for triceps skinfold thickness, -0.59 ± 0.63 (p-value = 0.0042) and for arm fat area -0.67 ± 0.67 (p-value = 0.0061). CONCLUSION: 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.

OBJETIVO: Embora a síndrome de Williams-Beuren seja bem conhecida, há apenas um estudo descrevendo a composição corporal nesses pacientes. O objetivo foi caracterizar o estado nutricional de brasileiros com síndrome de Williams. MÉTODOS: Utilizou-se um estudo transversal com a avaliação de dados clínicos e nutricionais de 17 pacientes. Foram calculados os escores-z do peso, estatura, índice de massa corpórea, dobras cutâneas, circunferência do braço e áreas muscular e adiposa do braço. Para verificar diferenças, foi utilizado o teste de Wilcoxon, sendo considerado significativo p < 0,05. RESULTADOS: Os valores médios dos escores-z foram: -1,14 ± 1,00 (p = 0,004) para estatura, -0,67 ± 1,19 (p = 0,0443) para peso, -0,94 ± 1,14 (p = 0,0222) para a circunferência do braço, -0,59 ± 0,63 (p = 0,0042) para dobra cutânea do tríceps e -0,67 ± 0,67 (p = 0,0061) para a área gordurosa do braço. Foi observada desnutrição pregressa em quatro pacientes e crônica, em dois. CONCLUSÃO: A baixa estatura, semelhante à descrita na população alemã, parece ser intrínseca à síndrome. Esse foi o primeiro estudo que avaliou a composição corporal, utilizando as dobras cutâneas, e detectou anormalidades nas reservas de gordura. O método aqui utilizado é simples, rápido e de baixo custo, facilitando estudos similares em outras populações. Isso poderia melhor caracterizar esses aspectos na síndrome de Williams. Morbidade relacionada a essa doença e informações para investigação e seguimento clinico são discutidas.

Anthropometric and body-mass composition suggests an intrinsic feature in Williams-Beuren syndrome.

OBJECTIVE: Although considered a well-known condition, there is only one study describing the body composition among individuals with Williams-Beuren syndrome. The aim was to characterize the nutritional status in Brazilian individuals with this condition. METHODS: Cross-sectional study was designed to evaluate clinical and nutritional data of 17 Brazilian patients. Z-scores for height, weight, body mass index, triceps and subscapular skinfold thickness, arm circumference, arm muscle area, arm fat area were calculated. Wilcoxon's test was used to investigate differences between the z-scores of the anthropometrical measures and zero. RESULTS: Four children were considered stunted and two severely malnourished. The z-score mean value for height was -1.14 ± 1.00 (p-value = 0.004), for weight, -0.67 ± 1.19 (p-value = 0.0443), for arm circumference, -0.94 ± 1.14 (p-value = 0.0222), for triceps skinfold thickness, -0.59 ± 0.63 (p-value = 0.0042) and for arm fat area -0.67 ± 0.67 (p-value = 0.0061). CONCLUSION: 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.