Cytogenetic and molecular characterization of an SRY-negative 46, XX ovotesticular DSD: a case report / Caracterização citogenética e molecular de um DDS ovotesticular 46, XX SRY-negativo: relato de caso

Introduction: Ovotesticular disorder of sex development is a rare condition characterized by the concomitant presence of testicular and ovarian tissue, and usually presents genital ambiguity. They are chromosomally heterogeneous, and cytogenetic analyses is relevant. Objective: to report a patient from Manaus, Amazonas state, Brazil, with ovotesticular disorder of sex differentiation 46,XX and SRY-negative. Case report: patient aged 19 years, first child of non-consanguineous parents, diagnosed at birth with genital ambiguity and, without correct diagnosis, was registered a male sex. The patient underwent surgery to correct bilateral cryptorchidism, orchiopexy and colpectomy. During puberty, he developed female and male sexual characteristics. Investigation at this time revealed: laboratory (normal total testosterone and estradiol as high follicle-stimulating hormone and luteinizing hormone, histopathological (right gonad, ovarian follicles and left gonad, atrophic testicles), karyotype (46, XX) and molecular (SRY-negative). Diagnosis of ovotesticular disorder of sex development was established. The patient chose to remain male and underwent bilateral mastectomy, vaginal colpectomy and bilateral gonadectomy. Currently, the patient receives hormonal replacement therapy, followup with a multi-professional approach and awaits masculinizing genitoplasty. Discussion: For OT-DSD individuals with 46, XX, the female sex is suggested as the best sex of rearing option. Unlike the reported cases, the patient chose the male sex, since the sex at registration of birth was important in his choice. Conclusion: Cytogenetic and molecular analyses allowed us to assist in the etiological diagnosis of the patient with OT-DSD. However, molecular analyses are necessary to elucidate the genes involved in the sexual determination of this patient.

Introdução: distúrbio da diferenciação do sexo ovotesticular é uma condição rara com presença concomitante de tecido testicular e ovariano, geralmente com ambiguidade genital. Os pacientes são cromossomicamente heterogêneos e a análise citogenética é fundamental. Objetivo: relatar o caso de um paciente do município de Manaus, Amazonas, portador de distúrbio da diferenciação do sexo ovotesticular 46, XX e SRY-negativo. Caso clínico: paciente de 19 anos, primeiro filho de pais não consanguíneos, que ao nascimento foi diagnosticado com ambiguidade genital, contudo, sem diagnóstico correto, foi registrado como sendo do sexo masculino. Foi submetido a cirurgias para correção da criptoquirdia bilateral, orquidopexia e colpectomia vaginal. Na puberdade, desenvolveu características sexuais feminina e masculina. Investigação diagnóstica mostrou: exames hormonais (testosterona total e estradiol normais enquanto hormônio folículo-estimulante e hormônio luteinizante elevados), histopatológicos (gônada direita, folículos ovarianos e gônadas esquerda, testículos atróficos), cariótipo (46, XX) e molecular (SRY-negativo). O diagnóstico de distúrbio da diferenciação do sexo ovotesticular foi estabelecido. O paciente optou por permanecer no sexo masculino e submeteuse à mastectomia bilateral, colpectomia vaginal e gonadectomia bilateral. Atualmente faz reposição hormonal, acompanhamento com abordagem multiprofissional e aguarda pela genitoplastia masculinizante. Discussão: aos indivíduos DDS-OT com 46, XX é sugerido como a melhor opção de sexo, o feminino. Diferentemente dos casos relatados, o paciente optou por permanecer no sexo masculino, visto que o registro de nascimento foi importante para a sua escolha. Conclusão: análises citogenéticas e moleculares permitiu auxiliar no diagnóstico etiológico do paciente com DDS-OT, contudo, análises moleculares são necessárias para elucidação de genes envolvidos na determinação sexual desse paciente.

Síndrome de deleção 6q: relato de caso de um achado raro no Amazonas, Brasil / Deletion 6q syndrome: case report of a rare finding in Amazonas, Brazil

Objetivos: Síndrome da deleção 6q é considerada uma anomalia cromossômica rara. Assim, nosso objetivo foi relatar um caso de um menino com essa síndrome, em Manaus/Amazonas. Descrição do caso: Menino com quatro anos de idade que apresenta atraso do crescimento e do desenvolvimento neuropsicomotor, dificuldades de ganho de peso e anormalidades na retina. A análise citogenética do paciente revelou cariótipo com 46, XY, del(6)(q25-qter). Conclusões: Este relato demonstrou a importância das análises citogenéticas para o diagnóstico preciso das anomalias congênitas, pois auxiliam no encaminhamento de tratamentos adequados aos pacientes e na ampliação de conhecimento científico relacionado a essa deleção.

Aims: Deletion 6q syndrome is considered a rare chromosomal anomaly. Thus, our objective was to report a rare case of a boy with 6q deletion syndrome. Case description: 4-year-old boy with delayed growth and neuropsychomotor development, weight gain difficulties and retinal abnormalities. Karyotypic analysis of the patient revealed karyotype 46, XY, del (6) (q25-qter). That is, a deletion in the long arm of one of the chromosome 6, specifically in the distal region of the long arm of the 6q25 band up to the 6qter band. Conclusions: This report demonstrates the importance of cytogenetic analyzes for the accurate diagnosis of congenital anomalies, as they assist in referring appropriate treatments to patients and in expanding scientific knowledge related to this deletion.

Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1ß, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. RESULTS: Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. CONCLUSION: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

Syndrome in question

Costello syndrome (CS) is a rare genetic disorder, first described by Costello in 1971, caused by mutations in the HRAS proto-oncogene. Clinical findings include facial dysmorphism, skin disorders, cognitive impairment, cardiac and musculoskeletal defects. There is an increased risk of malignancies in these patients, due to the proto-oncogene mutation, and also sudden death secondary to heart disease. We report a case with characteristic phenotype, highlighting the peculiar skin changes.

Syndrome in question. Costello syndrome.

Costello syndrome (CS) is a rare genetic disorder, first described by Costello in 1971, caused by mutations in the HRAS proto-oncogene. Clinical findings include facial dysmorphism, skin disorders, cognitive impairment, cardiac and musculoskeletal defects. There is an increased risk of malignancies in these patients, due to the proto-oncogene mutation, and also sudden death secondary to heart disease. We report a case with characteristic phenotype, highlighting the peculiar skin changes.