RESUMO
OBJECTIVE: SRY-negative 46,XX testicular and ovotesticular disorders/differences of sex development (T/OTDSD) represent a very rare and unique DSD condition where testicular tissue develops in the absence of a Y chromosome. To date, very few studies have described the phenotype, clinical and surgical management and long-term outcomes of these patients. Particularly, early blockade of the gonadotropic axis in patients raised in the female gender to minimize postnatal androgenization has never been reported. DESIGN: Retrospective description of sixteen 46,XX T/OTDSD patients. RESULTS: Sixteen 46,XX SRY-negative T/OTDSD were included. Most (12/16) were diagnosed in the neonatal period. Sex of rearing was male for six patients and female for ten, while the clinical presentation varied, with an external masculinization score from 1 to 10. Five patients raised as girl were successfully treated with GnRH analog to avoid virilization during minipuberty. Ovotestes/testes were found bilaterally for 54% of the patients and unilaterally for the others (with a contralateral ovary). Gonadal surgery preserved appropriate tissue in the majority of cases. Spontaneous puberty occurred in two girls and one boy, while two boys required hormonal induction of puberty. One of the girls conceived spontaneously and had an uneventful pregnancy. DNA analyses (SNP-array, next-generation sequencing and whole-exome sequencing) were performed. A heterozygous frameshit mutation in the NR2F2 gene was identified in one patient. CONCLUSIONS: This study presents a population of patients with 46,XX SRY-negative T/OTDSD. Early blockade of gonadotropic axis appears efficient to reduce and avoid further androgenization in patients raised as girls.
Assuntos
Transtornos Ovotesticulares do Desenvolvimento Sexual , Feminino , Humanos , Recém-Nascido , Masculino , Ovário , Transtornos Ovotesticulares do Desenvolvimento Sexual/genética , Estudos Retrospectivos , TestículoRESUMO
Managing patients unable to produce sex steroids using gonadotropins to mimic minipuberty in hypogonadotropic hypogonadism, or sex steroids in patients with Klinefelter or Turner syndrome, is promising. There is a need to pursue research in this area, with large prospective cohorts and long-term data before these treatments can be routinely considered.
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Hipogonadismo , Síndrome de Klinefelter , Síndrome de Turner , Humanos , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/complicações , Hipogonadismo/tratamento farmacológico , Hipogonadismo/etiologia , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/tratamento farmacológico , Lactente , Masculino , Pré-Escolar , Feminino , Terapia de Reposição Hormonal/métodos , Criança , Gonadotropinas/uso terapêuticoRESUMO
Transgender children and adolescents can be supported in France by multidisciplinary teams since the creation of dedicated consults in 2014. The personalized support provided relies on international recommendations based on scientific studies that have demonstrated the beneficial impact of such support in the short and medium term. However, many ethical and medical questions remain, particularly on the long-term effects of treatments or the impact on fertility. The continuing accumulation of data will provide these young people and their families with the most enlightened information possible.
Title: Accompagnement des transidentiteés chez l'enfant et l'adolescent(e). Abstract: Depuis la création de consultations dédiées en 2014, les enfants et adolescent(e)s transgenres peuvent être accompagnés en France par des équipes pluridisciplinaires. L'accompagnement personnalisé qui s'y est développé s'appuie sur des recommandations internationales, reposant elles-mêmes sur des études scientifiques qui ont démontré l'impact bénéfique d'un tel accompagnement à court et moyen termes. De nombreuses questions persistent néanmoins, à la fois médicales, en particulier sur les effets à long terme des traitements ou l'impact sur la fertilité, mais aussi éthiques. L'accumulation de données au long cours permettra d'apporter à ces jeunes et à leur famille les informations les plus éclairées possibles.
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Pessoas Transgênero , Criança , Adolescente , Humanos , Fertilidade , França , Princípios Morais , Encaminhamento e ConsultaRESUMO
Turner syndrome (TS; ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 1/2500 liveborn girls. The most frequently observed karyotypes are 45,X (40-50%) and the 45,X/46,XX mosaic karyotype (15-25%). Karyotypes with an X isochromosome (45,X/46,isoXq or 45,X/46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweight/obesity, glucose intolerance/type 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are designed to provide such support.
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Diabetes Mellitus Tipo 2 , Síndrome de Turner , Adulto , Cromossomos Humanos X/genética , Feminino , Humanos , Cariótipo , Cariotipagem , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Síndrome de Turner/terapiaRESUMO
Objective Turner Syndrome is associated with several phenotypic conditions associated with a higher risk of subsequent comorbidity. We aimed to evaluate the prevalence of congenital malformations and the occurrence of age-related comorbid conditions and to determine whether the frequencies of congenital and acquired conditions depend on X chromosome gene dosage, as a function of karyotype subgroup. Design and methods This national retrospective observational cohort study includes 1501 patients. We evaluated the prevalence of congenital malformations and the cumulative incidence of subsequent specific comorbidities at five-year intervals, from the ages of 10 to 30 years, with stratification by karyotype subgroup: 45,X (n = 549), 45,X/46,isoXq (n = 280), 46,X,r(X)/46,XX (n = 106), 45,X/46,XX (n = 221), presence of Y (n = 87). Results Median age was 9.4 (3.7-13.7) years at first evaluation and 16.8 (11.2-21.4) years at last evaluation. Congenital heart (18.9%) malformations were more frequent in 45,X patients, and congenital renal (17.2%) malformations were more frequent in 45,X, 45,X/46,isoXq and 46,X,r(X)/46,XX patients than in those with 45,X/46,XX mosaicism or a Y chromosome (P < 0.0001). The cumulative incidence of subsequent acquired conditions, such as thyroid disease, hearing loss, overweight/obesity, dyslipidemia and, to a lesser extent, celiac disease, glucose intolerance/type 2 diabetes, hypertension and liver dysfunction increased with age, but less markedly for patients with mosaicism than for those with other karyotypes. Patients with a ring chromosome were more prone to metabolic disorders. Conclusion These data suggest that X gene chromosome dosage, particularly for Xp genes, contributes to the risk of developing comorbidities.
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Cromossomos Humanos X/genética , Anormalidades Congênitas/genética , Dosagem de Genes , Síndrome de Turner/genética , Adolescente , Adulto , Fatores Etários , Criança , Estudos de Coortes , Comorbidade , Anormalidades Congênitas/epidemiologia , Feminino , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Humanos , Cariótipo , Rim/anormalidades , Nefropatias/congênito , Nefropatias/epidemiologia , Nefropatias/genética , Mosaicismo , Estudos Retrospectivos , Fatores de Risco , Síndrome de Turner/classificação , Síndrome de Turner/complicações , Adulto JovemRESUMO
OBJECTIVE: Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment. DESIGN: We conducted a national observational multicenter study. METHODS: Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%). RESULTS: Birth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome. CONCLUSION: These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy.