SRY ‐negative 46,XX testicular/ovotesticular DSD: Long‐term outcomes and early blockade of gonadotropic axis
Autor: | Cécile Brachet, Michel Peuchmaur, Juliane Léger, Capucine Hyon, Jean-Claude Carel, Claire Bouvattier, Alaa El Ghoneimi, Matthieu Peycelon, Dominique Simon, Ken McElreavey, Jérôme Bouligand, Jean-Pierre Siffroi, Dinane Samara-Boustani, Annabel Paye-Jaouen, Laurence Dumeige, Sophie Lambert, Laetitia Martinerie, Elodie Fiot |
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Přispěvatelé: | Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Clinique CHC MontLégia [Liège, Belgium], Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Service d'endocrinologie, gynécologie et diabétologie pédiatriques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Pathologie [Hôpital Robert Debré - APHP], Sorbonne Paris Cité-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Génétique Moléculaire Pharmacogénétique et Hormonologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), UF de Génétique chromosomique [CHU Trousseau], Institut Pasteur [Paris] (IP), GHU AP-HP Centre Université de Paris, Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Couvet, Sandrine, Maladies génétiques d'expression pédiatrique (U933), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique du Développement humain - Human developmental genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism media_common.quotation_subject [SDV]Life Sciences [q-bio] Population 030209 endocrinology & metabolism Ovary [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics Y chromosome 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Testis medicine Humans Girl education testicular DSD media_common Retrospective Studies Gynecology Pregnancy education.field_of_study minipuberty business.industry Virilization XX-SRY-negative DSD Infant Newborn medicine.disease Blockade Ovotesticular Disorders of Sex Development [SDV] Life Sciences [q-bio] GnRH analog Testis determining factor medicine.anatomical_structure [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics 030220 oncology & carcinogenesis Female ovotesticular DSD medicine.symptom business |
Zdroj: | Clinical Endocrinology Clinical Endocrinology, 2021, 94 (4), pp.667-676. ⟨10.1111/cen.14389⟩ |
ISSN: | 0300-0664 1365-2265 |
Popis: | International audience; 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. |
Databáze: | OpenAIRE |
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