RESUMO
Copy number variations of several genes involved in the process of gonadal determination have been identified as a cause of 46,XY differences of sex development. We report a non-syndromic 14-year-old female patient who was referred with primary amenorrhea, absence of breast development, and atypical genitalia. Her karyotype was 47,XY,+mar/46,XY, and FISH analysis revealed the X chromosome origin of the marker chromosome. Array-CGH data identified a pathogenic 2.0-Mb gain of an Xp21.2 segment containing NR0B1/DAX1 and a 1.9-Mb variant of unknown significance from the Xp11.21p11.1 region. This is the first report of a chromosomal microarray analysis to reveal the genetic content of a small supernumerary marker chromosome detected in a 47,XY,+der(X)/46,XY karyotype in a non-syndromic girl with partial gonadal dysgenesis and gonadoblastoma. Our findings indicate that the mosaic presence of the small supernumerary Xp marker, encompassing the NR0B1/DAX1 gene, may have been the main cause of dysgenetic testes development, although the role of MAGEB and other genes mapped to the Xp21 segment could not be completely ruled out.
Assuntos
Disgenesia Gonadal 46 XY , Gonadoblastoma , Neoplasias Ovarianas , Adolescente , Receptor Nuclear Órfão DAX-1/genética , Variações do Número de Cópias de DNA , Feminino , Disgenesia Gonadal 46 XY/genética , Gonadoblastoma/genética , Humanos , CariótipoRESUMO
OBJECTIVE: To evaluate the odds of a behavioral health diagnosis among youth with differences of sex development (DSD) or congenital adrenal hyperplasia (CAH) compared with matched controls in the PEDSnet database. STUDY DESIGN: All youth with a diagnosis of DSD (n = 1216) or CAH (n = 1647) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables (1:4) with controls (n = 4864 and 6588, respectively) using multivariable logistic regression. The likelihood of having behavioral health diagnoses was examined using generalized estimating equations. RESULTS: Youth with DSD had higher odds of a behavioral health diagnosis (OR, 1.7; 95% CI, 1.4-2.1; P < .0001) and neurodevelopmental diagnosis (OR, 1.7; 95% CI, 1.4, 2.0; P < .0001) compared with matched controls. Youth with CAH did not have an increased odds of a behavioral health diagnosis (OR, 1.0; 95% CI, 0.9, 1.1; P = .9) compared with matched controls but did have higher odds of developmental delay (OR, 1.8; 95% CI, 1.4, 2.4; P < .0001). CONCLUSIONS: Youth with DSD diagnosis have higher odds of a behavioral health or neurodevelopmental diagnosis compared with matched controls. Youth with CAH have higher odds of developmental delay, highlighting the need for screening in both groups.