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
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
Externí odkaz: