Clinical management in mixed gonadal dysgenesis with chromosomal mosaicism: Considerations in newborns and adolescents.

Individuals born on the spectrum of genetic abnormalities known as mixed gonadal dysgenesis (MGD) have a wide range of anatomical findings and management can be challenging in the newborn and adolescent. Historically, many individuals with MGD have undergone gonadectomy to avert the risk of gonadal malignancy. However, gonadectomy deprives patients of the benefits of their endogenous hormones, potential fertility, and in the case with MGD, has historically been done prior to addressing gender identity. Some patient advocates have proposed a delayed approach to surgical reconstructions and/or gonadectomy in other differences/disorders of sex development (DSD), particularly in patients with congenital adrenal hyperplasia and androgen insensitivity syndrome. In many areas of the world, there continues to be a shift toward delayed reconstructions and hesitancy regarding irreversible gonadectomy. To date, no clinical management protocol addressing these issues from a patient-centered approach has been described. We review what is known about malignancy risk and propose a management protocol for those with MGD that involves shared decision making regarding the gonads and addresses the long-term challenges with regard to gender and anatomy.

The Dilemma of Sex of Rearing: A Case of a 45,X/46,XY Neonate with Hydrocolpos.

BACKGROUND: A rare disorder of sex development is 45,X/46,XY mosaicism, which is phenotypically very heterogenous, ranging from normal male (or female) to that of genital ambiguity of varying degrees. CASE: We report a case of a neonate with 45,X/46,XY mosaicism and hydrocolpos, and we point out the dilemma and the difficulty in gender assignment. SUMMARY AND CONCLUSION: Gender assignment of cases with frank genital ambiguity is often difficult to be determined, because several factors have to be taken into consideration, such as genital appearance, anticipated urological and sexual function, capacity for future fertility, gonadal malignancy risk, and psychosocial factors. A multidisciplinary approach is definitely needed in the management of such cases.

[The diagnosis, treatment and following up of 7 patients with 45, X/46, XY mixed gonadal dysgenesis].

OBJECTIVE: To investigate the clinical features, therapeutic regimens and follow-up information of patients with 45, X/46, XY mixed gonadal dysgenesis in order to improve the diagnosis and treatment of the disease. METHODS: We performed a retrospective review of patients with 45, X/46, XY mosaicism hospitalized in Chinese PLA General Hospital between 2000 and 2014. The clinical features,sex hormones,treatment and follow-up information were summarized. RESULTS: (1) Seven patients ranging 12-17 years old were diagnosed as having 45, X/46, XY mixed gonadal dysgenesis. Six of them had female sex of rearing and one had male. (2) All of them presented with short stature and growth retardation, and had similar specific somatic signs to Turner syndrome. (3) The external genitalia presented with a wide variety of phenotypes. One patient presented with male phenotype with hypospadia, one presented with clitoridauxe, and five presented with female phenotype. The masculinization scores for the external genitalia showed that five patients presented with female phenotype, one patient with mild undervirilization and one patient with ambiguous genitalia. (4) By surgical exploration and ultrasound, two patients were found with testes and one was with ovary-like gonads. No gonad could be detected in the other four patients. (5) Five patients were treated with recombinant human growth hormone (rhGH). Two patients received sex hormone replacement therapy with one patient taking testosterone, whose penis became enlarged and erect after treatment, and one taking artificial cycle. CONCLUSIONS: The patients with 45, X/46, XY mosaicism share similar specific somatic signs to Turner syndrome. The 45, X/46, XY mosaicism presents with a wide spectrum of phenotypes with the highest proportion of being genital ambiguity. RhGH, testosterone and artificial cycle can be used accordingly.

Disgenesia gonadal mixta: ambigüedad genital. Urgencias y problemas diagnósticos / Mixed gonadal dysgenesia: genital ambigüity. Emergency and diagnostic problems

Presentamos un caso de Disgenesia Gonadal Mixta que anátomicamente presenta: ambigüedad de genitales externos con seno urogenital al que desemboca vagina, útero y trompas normales. La gónada derecha corresponde a testículo con extensas áreas de fibrosis y la izquierda a una gónada disgenética. La cromatina sexual fue positiva, también lo fue el Test de Hibridación in situ para la región centromérica de Cromosoma Y. El cariotipo determinó un mosaicismo 45 X (41 por ciento de las metafases estudiadas) / 46 X + marc (?Y). Se decidió la extirpación quirúrgica de ambas gónadas.

Disgenesia gonadal mixta: ambig³edad genital. Urgencias y problemas diagnósticos / Mixed gonadal dysgenesia: genital ambig³ity. Emergency and diagnostic problems

Presentamos un caso de Disgenesia Gonadal Mixta que anátomicamente presenta: ambig³edad de genitales externos con seno urogenital al que desemboca vagina, útero y trompas normales. La gónada derecha corresponde a testículo con extensas áreas de fibrosis y la izquierda a una gónada disgenética. La cromatina sexual fue positiva, también lo fue el Test de Hibridación in situ para la región centromérica de Cromosoma Y. El cariotipo determinó un mosaicismo 45 X (41 por ciento de las metafases estudiadas) / 46 X + marc (?Y). Se decidió la extirpación quirúrgica de ambas gónadas. (AU)

[45,X/46,XY/47,XXY chromosome mosaicism as a cause of hypergonadotropic hypogonadism diagnosed in late middle age]. / Chromosomenmosaik 45,X/46,XY/47,XYY als Ursache eines im höheren Lebensalter festgestellten hypergonadotropen Hypogonadismus.

UNLABELLED: HISTORY AND FINDINGS ON EXAMINATION: A 62-year-old man complaining of increasingly painful swelling in both breasts over the previous 6 months was admitted to hospital because an endocrine tumour or paraneoplasia was suspected. Unmarried and childless he had always been well except for mild diabetes treated with glibenclamide. On examination both breasts were enlarged with easily palpable glandular tissue; the testes were small and atrophic. Hair growth and distribution were normal. LABORATORY TESTS: Serum testosterone concentration was low (1.3 ng/ml), while luteinizing and follicle-stimulating hormones (27.3 mU/ml and 95 mU/ml, respectively) were raised. Chromosome analysis revealed 45,X/46,XY/47,XYY mosaicism without evidence of structural aberrations. Mammography showed true gynecomastia without signs of malignancy. TREATMENT AND COURSE: Hypergonadotrophic hypogonadism having been diagnosed the patient was given substitution treatment with 250 mg testosterone, 250 mg i.m. every 3 weeks. The concentrations of luteinizing and follicle-stimulating hormones became normal and the gynecomastia regressed over the subsequent 6 months. CONCLUSION: Mosaicism of the sex chromosomes should be considered in the differential diagnosis of late-onset hypogonadism, even in phenotypically unremarkable men.

Profile of intersex children in south India.

Thirty five children with ambiguous genitalia admitted to our centre between January 1986 to December 1991, were followed up and their clinical, laboratory and management strategies were analyzed. Most of them presented between 1 month and 2 years of age and only 2 presented in the newborn period. Sixteen were female pseudohermaphrodites. Eighteen out of 31 children were assigned female sex. One genetic female with congenital adrenal hyperplasia was assigned male sex. We practised more than one type of clitoroplasty in our centre. Parents prefer the intersex children to be reared as male possibly because of the less social stigma attached to an impotent male than to sterile female, and because males are socially independent.

Vaginoplastía y clitoroplastía: tratamiento a temprana edad / Vaginoplasty and clitoroplasty: treatment at small age

Se estudiaron 21 pacientes con diagnóstico de hiperplasis suprarrenal congénita, disgenesia gonadal mixta y hermafroditismo verdadero. Fueron sometidos a reconstrución genital mediante vaginoplastía y clitoroplastía. Se recomienda la reconstrucción temprana, es decir, antes de los 18 meses de vida en pacientes que presentan un seno urogenital y desembocadura de la vagina distal al cuello vesical. Se analizan los diferentes métodos de estudio; ultrasonido pélvido, genitograma y endoscopía. La edad promedio de operación fué de 15.1 meses. Se obtuvieron buenos resultados y complicaciones mínimas, por lo que se recomienda este tipo de tratamiento en edades tempranas.

[Asymmetrical gonadal dysgenesis. Report of a case (author's transl)]. / Dysgénésie gonadique mixte asymétrique. Etude anatomoclinique d'un cas.

The authors report a case of asymmetrical gonadal dysgenesis related to 45XO-46XY mosaicism in a 16 year old girl. Delayed growth and puberty, Turner's dysmorphism without sexual ambiguity and skeletal abnormalities are the main clinical features suggesting the diagnosis. Exploratory laparotomy reveals infantil uterus, bilateral fallopian tubes and streak gonads. A right dysgenetic testis is identified on electron microscopic examination. Theories on pathogenesis of this unusual genetic defect are discussed.

Disgenesia gonadal mixta: aspecto biopsicosocial, dignóstico y tratamiento / Mixed gonadal dysgenesis: biopsychosocial aspect, diagnosis and treatment

Se presenta el caso de una paciente con trastornos en la diferenciación sexual con personalidad psicologicosocial femenina, que por medio de la cirugía y tratamiento hormonal se ajusta al anterior sexo: se logra el desarrollo mamario grado II-III de Zeller; se refiere sangramiento genital periodico, con gran estabilidad emocional. Se pasan diapositivas y se exhibe película sobre este caso(AU)