RESUMEN
Ovotesticular difference of sex development (OT DSD) is a rare genetic disorder with an incidence of about 1/100,000 live births. The majority of OT DSD patients show a 46,XX karyotype, others may have 46,XX/46,XY chimerism or exhibit various mosaic sex chromosome combinations, and less commonly they may have a 46,XY karyotype. The aim of this work is to report the clinical, pathological, and karyotypic variations in OT DSD patients diagnosed among a large cohort of DSD patients. The study included 10 patients thoroughly evaluated for clinical, genital, and hormonal abnormalities and subjected to imaging studies, laparoscopy with gonadal biopsy, karyotype, and FISH analysis. The current study revealed a greater percentage of mosaic cell line combinations than previously reported and showed variable cytogenetic abnormalities, including the rare isodicentric (Y)(p11.32) abnormality and X;Y translocation. The study also revealed a unique pattern of gonadal type and combination frequencies. To our knowledge, this is the first study on OT DSD patients among a large cohort of DSD patients in Egypt and the Middle East.
RESUMEN
Sex chromosome mosaicism results in a large clinical spectrum of disorders of sexual development (DSD). The percentage of 45,X cells in the developing gonad plays a major role in sex determination. However, few reports on the gonadal mosaic status have been published, and the phenotype is usually correlated with peripheral lymphocyte karyotypes, which makes the phenotype prediction imprecise. This study was conducted on 7 Egyptian DSD patients to demonstrate the effect of sex chromosome constitution of both blood lymphocytes and gonadal tissues on the phenotypic manifestations. Conventional cytogenetic and FISH analyses of blood lymphocytes were conducted, and laparoscopy with gonadal biopsy was performed for histopathologic examination and FISH analysis. Gonosomal mosaicism was detected in 3 patients who had a non-mosaic chromosome pattern in blood lymphocytes. Two patients showed the same type of sex chromosome mosaicism in both the blood and gonadal tissues but with different distributions. Two other patients revealed a non-mosaic pattern in both tissues. The present study elucidates the importance of examining sex chromosome mosaicism in gonadal tissues of DSD patients and highlights the critical role of 45,X mosaicism which can lead to serious effects during early gonadal organogenesis.
Asunto(s)
Trastornos del Desarrollo Sexual/genética , Cariotipificación , Mosaicismo , Fenotipo , Cromosomas Sexuales/genética , Adolescente , Niño , Preescolar , Cromosomas Humanos X/genética , Egipto , Femenino , Gónadas/embriología , Gónadas/patología , Gónadas/ultraestructura , Humanos , Hibridación Fluorescente in Situ , Lactante , Linfocitos/ultraestructura , Masculino , Organogénesis , Cromosomas Sexuales/ultraestructura , Desarrollo Sexual/genéticaRESUMEN
Isodicentric chromosome formation is the most common structural abnormality of the Y chromosome. As dicentrics are mitotically unstable, they are subsequently lost during cell division resulting in mosaicism with a 45,X cell line. We report on six patients with variable signs of disorders of sex development (DSD) including ambiguous genitalia, short stature, primary amenorrhea, and male infertility with azoospermia. Cytogenetic studies showed the presence of a sex chromosome marker in all patients; associated with a 45,X cell line in five of them. Fluorescence in situ hybridization (FISH) technique was used to determine the structure and the breakage sites of the markers that all proved to be isodicentric Y chromosomes. Three patients, were found to have similar breakpoints: idic Y(qterâ p11.32:: p11.32â qter), two of them presented with ambiguous genitalia and were found to have ovotesticular DSD, while the third presented with short stature and hypomelanosis of Ito. One female patient presenting with primary amenorrhea, Turner manifestations and ambiguous genitalia revealed the breakpoint: idic Y (pterâq11.1::q11.1âpter). The same breakpoint was detected in a male with azoospermia but in non-mosaic form. An infant with ambiguous genitalia and mixed gonadal dysgenesis (MGD) had the breakpoint at Yq11.2: idic Y(pterâq11.2::q11.2âpter). SRY signals were detected in all patients. Sequencing of the SRY gene was carried out for three patients with normal results. This study emphasizes the importance of FISH analysis in the diagnosis of patients with DSD as well as the establishment of the relationship between phenotype and karyotype.
Asunto(s)
Cromosomas Humanos Y , Trastornos del Desarrollo Sexual/genética , Aberraciones Cromosómicas Sexuales , Adolescente , Adulto , Niño , Preescolar , Bandeo Cromosómico , Trastornos del Desarrollo Sexual/diagnóstico , Egipto , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Cariotipo , Masculino , Fenotipo , Adulto JovenRESUMEN
BACKGROUND: Although the cardiovascular effect of CO2 insufflation has not been reported in pediatric thoracoscopy, several clinical trials have demonstrated significant hemodynamic deterioration in adults. We investigated the concept of therapeutic hypercapnia for counteracting the hemodynamic effect of induced capnothorax. METHODS: Twelve pediatric patients who underwent video-assisted thoracoscopic patent ductus arteriosus closure were enrolled in the study. Cardiorespiratory variables were determined during baseline T1 and after CO2 insufflation at pressures of 2 mm Hg T2, 4 mm Hg T3, 6 mm Hg T4, 8 mm Hg T5, and 10 mm Hg T6. RESULTS: CO2 insufflation was not associated with any adverse hemodynamic effects. Cardiac output and central venous oxygen saturation increased progressively throughout the study protocol. Relative to baseline peak velocity, systolic flow time corrected for heart rate, heart rate, and central venous pressure increased significantly during insufflation, but systolic and diastolic blood pressure remained unchanged. Arterial CO2 increased from 40.7 +/- 3 at T1 to 61 +/- 1.6 at T6 mm Hg. Arterial oxygen tension increased from 170.9 +/- 3.3 at T1 to 182 +/- 2 at T6; arterial PH decreased from 7.31 +/- 1.2 at T1 to 7.14 +/- 4.6 at T6. CONCLUSION: Hypercapnia targeting CO2 50-70 mm Hg was associated with increased cardiac output, central venous O2, and arterial O2 tension in patients undergoing video-assisted thoracoscopic patent ductus arteriosus closure using one-lung ventilation without any deleterious cardiopulmonary effects.
Asunto(s)
Acidosis Respiratoria/fisiopatología , Dióxido de Carbono/administración & dosificación , Conducto Arterioso Permeable/cirugía , Hemodinámica , Hipercapnia/fisiopatología , Insuflación , Neumotórax Artificial , Cirugía Torácica Asistida por Video , Acidosis Respiratoria/sangre , Acidosis Respiratoria/diagnóstico por imagen , Adolescente , Velocidad del Flujo Sanguíneo , Gasto Cardíaco , Presión Venosa Central , Niño , Conducto Arterioso Permeable/sangre , Conducto Arterioso Permeable/diagnóstico por imagen , Conducto Arterioso Permeable/fisiopatología , Femenino , Frecuencia Cardíaca , Humanos , Hipercapnia/sangre , Hipercapnia/diagnóstico por imagen , Cuidados Intraoperatorios , Masculino , Oxígeno/sangre , Estudios Prospectivos , Ultrasonografía Doppler DúplexRESUMEN
A small infant with congenital cystic adenomatoid was scheduled for thoracoscopic resection of the lung cyst. During carbon dioxide insufflation, there was a sharp rise of endtidal carbon dioxide which was followed by marked hypoxemia and bradycardia due to occlusion of the tracheal tube with blood. The plan changed to open thoracotomy and total pneumonectomy. Despite several reports, which addressed successful thoracoscopic cystic lung resection, its safety remain to be determined.