ESPU Meeting on Thursday 4, September 2025, 14:50 - 15:30
14:50 - 14:53
S13-1 (OP)
Nico LOURENS 1, Yazan RAWASHDEH 2, Claus Højbjerg GRAVHOLT 3, Jesper JUST 3 and Emma Marie Bruun JOHANNSEN 3
1) Aarhus University/University of Pretoria, Department of Molecular Medicine (MOMA), Aarhus, DENMARK - 2) Aarhus University, Department of Paediatric Urology, Aarhus, DENMARK - 3) Aarhus University, Department of Molecular Medicine (MOMA), Aarhus, DENMARK
PURPOSE
We studied the genetic makeup of OT-DSD patients from a well-defined area within eastern South Africa with high incidences of DSD. Next generation RNA sequencing was undertaken on 14 gonadal biopsies of patients with OT-DSD managed from the aforementioned area to evaluate gene profile expressions.
MATERIAL AND METHODS
Gonadal biopsies in patients with confirmed ovotesticular DSD were evaluated morphologically and by Illumina RNA-Seq analysis. Relative gene expression for pro-ovarian and protesticular markers were assessed
RESULTS
Results revealed global over expression of pro-ovarian and under expression of pro-testis
genes respectively. Morphology could not reliably identify which gonads were pure ovary, pure testis, or intermixed ovotestis, and gonads often differed in the same patient. Furthermore, a single genetic cause was not responsible but it appears that groups of genes seem to work in concert to mediate pro-testis gene expression
CONCLUSIONS
Intermixed ovotestis often harbour sites of hidden ovarian or testicular tissue, which is easy to miss on morphology. Furthermore, in this case series the expression of ovarian and absence of testicular genes seem to be driving the development of ovotestes. No single gene or gene product seems to be the cause, but rather groups of genes and their effects
14:53 - 14:56
S13-2 (OP)
Emilie JOHNSON 1, Allison GOETSCH WEISMAN 2, Ashley TALTON 1, Josephine HIRSCH 3, Ilina ROSOKLIJA 1, Nicolas PORTA 4, Monica LARONDA 5, Jaclyn PAPADAKIS 6 and Courtney FINLAYSON 7
1) Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Urology, Chicago, USA - 2) Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Genetics, Genomics, and Metabolism, Chicago, USA - 3) Lurie Children's Hospital, Urology, Chicago, USA - 4) Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Neonatology, Chicago, USA - 5) Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Surgery, Chicago, USA - 6) Ann & Robert H. Lurie Children's Hospital of Chicago, Pritzker Department of Psychiatry and Behavioral Health, Chicago, USA - 7) Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Endocrinology, Chicago, USA
PURPOSE
Patients with suspected differences of sex development (DSD) frequently face a stressful diagnostic testing odyssey; yet less than half currently receive a genetic diagnosis. Whole genome sequencing (WGS) broadly evaluates for pathogenic genetic changes, with results in about one month. This pilot study aimed to explore the potential role of whole genome sequencing (WGS) to improve diagnostic yield and speed among patients with suspected DSD.
MATERIAL AND METHODS
Patients with suspected DSD and no genetic diagnosis were recruited. Demographic/clinical characteristics, prior genetic testing, and WGS results were summarized.
RESULTS
Of 27 patients approached, 13 enrolled (median age 4.3 years, 85% assigned male). Clinical characteristics: 92% 46,XY, 69% at least 1 comorbidity, 31% family history of DSD, 23% premature. Endocrine testing results: 38% gonadal dysfunction, 0% adrenal dysfunction. Before enrollment, eight patients (62%) had 14 genetic tests beyond karyotype, 10 of which could have been replaced by WGS. After enrollment, two patients had diagnostic WGS (one DHX37-, one SF1-associated 46,XY DSD), and two had possible diagnoses (SAMD9 variant of unknown significance (VUS): mild MIRAGE syndrome; KDM1A VUS). Two of these four patients had prior negative genetic testing. Three patients had non-DSD variants discovered that changed medical management. Seven had non-diagnostic WGS.
CONCLUSIONS
WGS is a feasible comprehensive genetic testing option for patients with suspected DSD. Nearly half of patients had clinically actionable diagnoses uncovered, including 31% with a known/possible DSD. WGS demonstrated potential for reduced number of diagnostic tests among patients with and without a diagnosis uncovered.
14:56 - 14:59
S13-3 (OP)
Yannis BONNIN 1, Valeska BIDAULT 2, Anne BERGOUGNOUX 3, Benoit TESSIER 1, Christine LEFEVRE 4, Claire BOUVATIER 5, Alexis ARNAUD 6, Silvia PECORELLI 7, Ichrak BELBAHRI 8, Diana POTOP 9, Aurélie CAZALS 1, Jean-Michel FAURE 10, Florent FUCHS 10, Laura GASPARI SULTAN 11, Patricia BRETONES 12, Françoise PARIS 11, Jérôme MASSARDIER 13 and Nicolas KALFA 1
1) Hôpital Lapeyronie, CHU Montpellier, Service de Chirurgie Viscérale et Urologique pédiatrique, Montpellier, FRANCE - 2) Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Service de chirurgie uro-viscérale, thoracique et de transplantation de l'enfant, Bron, FRANCE - 3) CHU Montpellier, Unité de Génétique Moléculaire - IURC, Montpellier, FRANCE - 4) Hôpital Jeanne de Flandre, CHU Lille, Service d'Endocrinologie Pédiatrique, Lille, FRANCE - 5) Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Endocrinologie et diabète de l'Enfant, Le Kremlin-Bicêtre, FRANCE - 6) CHU DE RENNES, Chirurgie pédiatrique, Rennes, FRANCE - 7) HÔPITAL DES ENFANTS - GROUPE HOSPITALIER PELLEGRIN, CHU BORDEAUX, Service de Chirurgie Viscérale, Urologique et Plastique de l'Enfant et de l'Adolescent, Bordeaux, FRANCE - 8) Hôpital des enfants, CHU Toulouse, Pédiatrie - Chirurgie viscérale, Toulouse, FRANCE - 9) CHU de Poitiers, Service de Chirurgie Pédiatrique, Poitiers, FRANCE - 10) Hôpital Lapeyronie, CHU Montpellier, Service de Gynécologie-Obstétrique, Médecine Maternelle et Foetale, Montpellier, FRANCE - 11) Hôpital Lapeyronie, CHU Montpellier, Service d'Hormonologie du développement et de la reproduction, Montpellier, FRANCE - 12) Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Service d'endocrinologie et de diabétologie pédiatriques et maladies héréditaires du métabolisme, Bron, FRANCE - 13) Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Service de gynécologie-obstétrique, Centre pluridisciplinaire de diagnostic prénatal (CPDPN), Bron, FRANCE
PURPOSE
Technological advancements make PD-DSD more common. Its reliability is sparsely reported and it remains difficult to rationalize prenatal counselling and fetal management. We aimed to analyze the 1-correlation between prenatal and postnatal findings, 2-prognostic factors for severe DSD, 3-rate of associated malformations.
MATERIAL AND METHODS
Multicenter retrospective study including fetuses with atypical genitalia during pregnancy (8 centers, 2003-2022). Pregnancy history, ultrasound findings and neonatal phenotype were collected using a form validated by a national multidisciplinary working group.
RESULTS
443 patients were included. Mean gestational age at diagnosis was 27+3 weeks, diagnosis was possible at any time (12-41w). The main circumstance of diagnosis was direct visualization of atypical genitalia (69%), including aspect of hypospadias (n=274), abnormal genital tubercle (n=113), genital swelling (n=107) or undetermined sex (n=24). Other circumstances included a discrepancy between chromosomal and ultrasound sex (3.9%) and the presence of other congenital defects leading to PD-DSD (25%). Overall, the positive predictive value of PN-DSD was 84%. Clinical spectrum at birth was wide, ranging from isolated anterior hypospadias to complex DSD. Risk factors for severe XY-DSD (posterior hypospadias and/or micropenis,n=230) were diagnosis at 1st trimester(p<0.001), aspect of posterior hypospadias on US(p<0.001) and presence of IUGR (p=0.01). Associated congenital defects were particularly frequent (n=182, 41.4%, identified syndrome 19%).
CONCLUSIONS
PD-DSD is reliable in 84% of cases. Minor or severe genitalia defects may be diagnosed. Early diagnosis, associated IUGR and aspect of posterior hypospadias are predictive of severe XY-DSD. Associated malformations are frequent. Next step is to determine which fetuses require prenatal molecular testing.
15:08 - 15:11
S13-4 (OP)
Frank-Mattias SCHÄFER 1, Benjamin SCHWAB-ECKHARDT 2, Egbert VOSS 3, Michael SCHROTH 4, Franz STAUDT 5 and Maximilian STEHR 2
1) Cnopfsche Kinderklinik, Paediatric Surgery & Urology, Nurnberg, GERMANY - 2) Cnopfsche Kinderklinik, Pediatric Surgery and Pediatric Urology, Nürnberg, GERMANY - 3) Cnopfsche Kinderklinik, Pediatric Endocrinology, Nürnberg, GERMANY - 4) Cnopfsche Kinderklinik, Pediatric Intensive Care and Neonatology, Nürnberg, GERMANY - 5) Master of Ethics, Ethics, Passau, GERMANY
PURPOSE
In recent years, changing cultural and scientific paradigms have fundamentally altered the approach to the treatment of children with Disorders of Sexual Development (DSD) prior to reaching the age of legal consent. In Germany, the situation changed with the introduction of legislation that includes a partial ban on DSD surgery in children in 2021. This study aims to analyze the impact of this legislation on clinical practice.
MATERIAL AND METHODS
From 2014 to 2024, all patients with DSD in our institution were included. The study group comprised all patients operated on after the legislation. All patients operated on before the legislation served as the control group. Karyotype, phenotype, resulting type of DSD, age at presentation and age at operation were recorded.
RESULTS
35 patients were included in this study, 15 in the study group and 20 in the control group. The operation was authorized by the family court for all patients in the study group. 46,XY patients with severe hypospadias were the largest proportion (25 patients, 71.4%). Nine patients (25.7%) were 46,XX girls with classical congenital adrenal hyperplasia (CAH) type. One patient (2.9%) showed a mixed gonadal dysgenesis. The mean age of the patients at first presentation was 10.7 months in the control group and 11.0 months in the study group. The mean age at operation was significantly higher in the study group (20.1 months) compared to the control group (15.1 months; p = 0.032, unpaired t-test).
CONCLUSIONS
The introduction of the legislation with a partial ban of genital surgery in DSD children in Germany has led to a significant delay in surgery. Since most patients have severe hypospadias and 46,XX CAH patients, exclusion of these diagnoses was proposed during mandatory evaluation of the law based on the results of this study. Further amendments or changes of the legislation based on this evaluation are pending.
15:11 - 15:14
S13-5 (OP)
Thomas BLANC 1, Claire BOUVATTIER 2, Lise DURANTEAU 3, Yves HÉLOURY 1, Dinane SAMARA BOUSTANI 4, Benjamin MORON PUECH 5, Jérôme BERTHERAT 6, Nicolas KALFA 7 and Anne Sophie JANNOT 8
1) Hopital Necker- Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paediatric Surgery & Urology, National Reference Center CRMERCD, Paris, FRANCE - 2) CHU Bicetre, Assistance Publique-Hôpitaux de Paris, Department of Pediatric Endocrinology, Reference Center for Rare Disease CRMR DevGen, Le Kremlin-Bicêtre, FRANCE - 3) CHU Bicetre, Assistance Publique-Hôpitaux de Paris, Department of Medical Gynecology, National Reference Center for DSD, Le Kremlin-Bicêtre, FRANCE - 4) Hopital Necker- Enfants Malades, Assistance Publique-Hôpitaux de Paris, Department of pediatric endocrinology, gynecology and diabetology, National Reference Center CRMERCD and PGR, Paris, FRANCE - 5) Université Lumière Lyon 2, CERCRID et Transversales, Lyon, FRANCE - 6) Hopital Cochin, Assistance Publique-Hôpitaux de Paris, Department of endocrinology, CNational Reference Center for Surrénale ; Génomique et Signalisation des Tumeurs Endocrines, Institut Cochin, INSERM U 1016, CNRS UMR8104, Université Paris Cité, Paris, FRANCE - 7) Hôpital Lapeyronie, CHU Montpellier, Department of Paediatric Surgery and Urology, ; DESP INSERM, Montpellier, France; National Reference Center for DSD DEVGEN Montpellier, Montpellier, FRANCE - 8) French National Rare Disease Registry, APHP, UMRS1346, Université Paris Cité, INRIA, INSERM, Paris, FRANCE
PURPOSE
The French Rare Diseases Registry collects a set of data for each person attending a rare disease expert centre in France, among them expert centres on Disorders of Sex Development (DSD). In this study, we analyse the surgical care pathway of children having severe DSD born in France, in the context of evolving regulations for genital surgical management.
MATERIAL AND METHODS
We included all children having severe DSD born between 2015 and 2020 from the French Rare Diseases Registry. Based on a linkage with the health national care claims data, we extracted information regarding genital surgical procedures during their first three years of life.
RESULTS
769 children were included, which leads to an estimated incidence of 1.7 cases per 10,000 births. 91% of them had one of the three following pathologies: posterior hypospadias of unknown aetiology (53%), congenital adrenal hyperplasia (21%), and gonadal dysgenesis (18%). The surgery rate at 3 years old for girls with congenital adrenal hyperplasia has significantly decreased from 50% for between 2015 and 2017 to 19% between 2018 and 2020, while the one for boys born with a posterior hypospadias has slightly decreased, from 89% to 83%.
CONCLUSIONS
A significant decrease in surgeries for children with marked DSD before the age of 3 is observed, especially for 46 XX DSD. This should be viewed in relation to the fact that the period covered by this study precedes the evolution of the French legislation, showing that pediatric surgeons and endocrinologists have changed their practices prior to the legislation.
15:14 - 15:19
S13-6 (VP)
Agustina Rene OLIVA 1, Pedro Luis MERCADO 2, Camila PERTIGA 2, Lucila PAVAN 3, Javier RUIZ 1, Francisco Ignacio DE BADIOLA 2, Roberto Luis VAGNI 1 and Maria ORMAECHEA 1
1) Hospital Italiano de Buenos Aires, Pediatric Urology, Capital Federal, ARGENTINA - 2) HIBA, Pediatric Urology, Caba, ARGENTINA - 3) HIBA, Ginecology, Caba, ARGENTINA
PURPOSE
The primary surgical technique in our institution for vaginoplasty in Rokitansky Syndrome (RS) has been coloplasty. We present a modified McIndoe technique, incorporating a graft of decellularized porcine small intestinal submucosa (SIS) with a 3D-printed mold to facilitate graft placement.
MATERIAL AND METHODS
We present a novel technique performed in a 17-year-old female patient with RS. It involved a SIS extracellular matrix positioned on a 3D-printed polylactic acid mold designed to prevent graft contraction and maintain both width and depth.
Surgical Technique: The vesico-rectal space was dissected meticulously, ensuring careful avoidance of the urethra and rectum. A vaginal canal measuring 9 cm in length and 4 cm in diameter was created. A 3D-printed vaginal mold, covered with a sterile condom, was inserted with the graft, sutured at its free edges positioned around the mold. It was then secured to the introitus circumference with interrupted non-absorbable sutures.
RESULTS
Four days postoperatively, the mold was removed, revealing a vital and adherent graft. Daily vaginal dilations were initiated. At first the vaginal canal exhibited adequate length but a minor constriction in its distal third, which was resolved by adjusting the size of the dilators. Aesthetic outcomes were satisfactory. A two-month vaginoscopy demonstrated a 9 cm neovagina with favorable diameter and early re-epithelization.
CONCLUSIONS
This modified McIndoe technique with SIS graft demonstrated excellent aesthetic results with minimal scarring and invasiveness. The integration of 3D printing technology facilitated the creation of customized molds, enhancing surgical precision. Long-term follow-up will assess functional and aesthetic outcomes.