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54th Annual ESPE

Barcelona, Spain
01 Oct 2015 - 03 Oct 2015

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Barcelona, Spain; 1-3 October 2015 Further information

hrp0084p2-303 | DSD | ESPE2015

Multiple Malformations Extending the Phenotypic Spectrum of Antley–Bixler Syndrome in a Patient with P450 Oxidoreductase Deficiency due to Two Novel Mutations of the POR Gene

Janchevska Aleksandra , Idkowiak Jan , Caredda Elisabeta , Hurst Jane , Dattani Mehul T , Arlt Wiebke , Spoudeas Helen A

Background: P450 oxidoreductase deficiency (PORD) is characterised by glucocorticoid and sex steroid deficiency and skeletal malformations, resembling Antley–Bixler syndrome (ABS, MIM 124015), a skeletal malformaton phenotype also present in patients with fibroblast growth factor receptor 2 mutations (FGFR2, MIM 176943). While genetic testing confirms both conditions, establishing the exact diagnosis on clinical grounds can be challenging.Objective ...

hrp0084p2-304 | DSD | ESPE2015

A Novel Homozygous Missense Mutation in RSPO1 Associated with a Familial Case of 46,XX Testicular and Ovotesticular DSD

Naasse Yassine , Jennane Farida , Hicham Sibai , McElreavey Ken , Bashamboo Anu

Background: RSPO1 is an activator of the canonical Wnt signalling pathway by acting as a ligand for LGR4–6 receptors and an a 46,XX individual it represses testicular development. Only three families have been reported in the literature with recessive mutations in RSPO1 and syndromic 46,XX sex-reversal.Objective and hypotheses: We identified a consanguineous family from Southern Morocco with two sibs presenting with 46,XX testicular and ovo...

hrp0084p2-305 | DSD | ESPE2015

‘’: An Online Database of Variants in Steroidogenic Factor 1 (SF-1, NR5A1) and Resource for Families and Professional Healthcare Providers

Suntharalingham Jenifer , Buonocore Federica , Duncan Andrew , Achermann John

Background: Steroidogenic factor 1 (SF1), encoded by the gene NR5A1, is a member of the orphan nuclear receptor superfamily and important regulator of gonadal and adrenal function. Variations in SF1 lead to a spectrum of conditions including 46,XY DSD, hypospadias, adrenal insufficiency, male factor infertility, and primary ovarian insufficiency. Inheritance patterns can be complicated (e.g. de novo dominant, sex-limited dominant, and autosomal recessive). In...

hrp0084p2-306 | DSD | ESPE2015

Two Testes and 2X Chromosomes: Why?

Aljaser Fahed , Wherrett Diane

Background: A 60-day-old infant with genital ambiguity was assessed in the multidisciplinary urogenital clinic. The baby was born full term and weighed 3.4 kg at birth. The antenatal history was noncontributory. On physical examination, there was no obvious dysmorphic features. On genitourinary exam, there was a well developed scrotum that was bifid, with rugae and pigmentation. There was penoscrotal transposition. His phallus was of a normal breadth and length with ventral cu...

hrp0084p2-307 | DSD | ESPE2015

Diagnostic Approach to a Newborn with Suspected DSD: Results From an International Survey of Specialist Care for DSD

Kyriakou Andreas , Dessens Arianne B , Bryce Jillian , Haraldsen Ira , Iotova Violeta , Juul Anders , Krawczynski Maciej , Nordenskjold Agneta , Rozas Marta , Sanders Caroline , Hiort Olaf , Ahmed S Faisal

Background: The approach to investigating a newborn with a suspected DSD is likely to vary between centres and may be influenced by local availability.Method: To explore the current diagnostic practice and needs, an international survey of 124 paediatric endocrinologists, identified through DSDnet and the I-DSD Registry, was performed in 2014.Results: A total of 77/124 (62%) clinicians, in 74 centres, from 38/42 (91%) countries res...

hrp0084p2-308 | DSD | ESPE2015

MAP3K1 Mutation in a Patient with Complete XY Gonadal Dysgenesis

Kohler Birgit , Gehrmann Nicole , Gruters-Kieslich Annette , Bignon-Topalovic Joelle , McElreavey Kenneth , Bashamboo Anu

Background: 49,XY gonadal dysgenesis (GD) is a very rare disorder of testes development with an incidence of 1:50–100 000. MAP3K1 is a MAPK that mainly regulates the MAPK pathways. High Map3k1 expression was found in female and male mice gonads at 13.5 dpc. In 2010, MAP3K1 mutations were identified in two families with complete and partial XY GD and in two unrelated sporadic cases with complete XY GD (Pearlman 2010 AJMG). Recently, four additional mutations (four out of 4...

hrp0084p2-309 | DSD | ESPE2015

Alterations in Germ Cell Memory and Mini-Puberty Induce Infertility in Cryptorchidism

Hadziselimovic Faruk , Docampo-Garcia Maria-Jose , Hadziselimovic Nils , Kray Gunthild , Demougin Philipp

Background: Spermatogonia contain processing bodies (P-bodies) that harbour P-element induced wimpy testis (Piwi) proteins associated specifically with Piwi-interacting RNAs to silence transposable DNA elements. In mice loss-of-function mutations in the Piwi pathway lead to de-repression of transposable elements, resulting in male-specific sterility.Objective and hypotheses: No previous studies have examined expression of transposons silencing gene micro...

hrp0084p2-310 | DSD | ESPE2015

Management of Gonads in Adults with Androgen Insensitivity: An International Survey

Maris Ellen , Looijenga L H J , Cools Martine

Background: Individuals with androgen insensitivity syndrome (AIS) have an increased risk for developing a germ cell cancer (GCC). The risk is low during childhood; therefore, gonads are commonly preserved until after puberty. Little is known about GCC development in AIS during adulthood. This question is particularly relevant as many adult AIS women decline gonadectomy.Objective and hypotheses: To gain insight in attitudes towards gonadectomy in various...

hrp0084p2-311 | DSD | ESPE2015

The Localisation of Cells with XX and XY in Gonadal Tissues Associated with Ovotesticular Disorder of Sexual Development with a 46,XX/46,XY Karyotype

Nishina Noriko , Fukuzawa Ryuji , Ishii Tomohiro , Hasegawa Tomonobu , Hasegawa Yukihiro

Background: Individuals with a mixed 46,XX and XY karyotype, categorized as ovotesticular disorder of sexual development (ODSD), have gonads with either an ovary in one side and a testis in the other side or an ovotestis.Objective and hypotheses: This study aimed to investigate the relationship between sex chromosomes and testicular and ovarian cell types in gonadal tissues associated with ODSD patients with 46,XX/46,XY.Method: Gon...

hrp0084p2-312 | DSD | ESPE2015

Birth Weight in Different Aetiologies of Disorder of Sex Development

Poyrazoglu Sukran , Darendeliler Feyza , Ahmed Syed Faisal , Bryce Jillian , Jiang Jipu , Rodie Martina , Hiort Olaf , Hannema Sabine E , Bertelloni Silvano , Lisa Lidka , Guran Tulay , Hughes Ieuan , Cools Martine , Chatelain Pierre , Claahsen-van der Grinten Hedi L , Nordenstrom Anna , Holterhus Paul-Martin , Kohler Birgit , Niedziela Marek , Krone Nils

Background: It is well known that boys are heavier than girls at birth. Causes of this difference are thought to originate from the Y chromosome and as a result of androgen action. Although some studies showed that sex dimorphism in size at birth is dependent of fetal androgens, one study reported that it is not generated by action of androgens.Objective and hypotheses: To determine birth weight (BW) of children in different aetiologies of disorder of se...

hrp0084p2-313 | DSD | ESPE2015

A Novel Human CYP19A1 Deletion-Insertion Mutation Reveals that the C-terminus of the Aromatase Protein is Crucial for its Activity

Ladjouze Asmahane , Sauter Kay-Sarah , Ouarezki Yasmine , Kedji Leila , Laraba Abdenour , Pandey Amit V , Fluck Christa E

Background: The steroidogenic enzyme aromatase is encoded by the CYP19A1 gene. Aromatase activity is required for estrogen biosynthesis from androgen precursors in the ovary and several extragonadal tissues. The role of aromatase and thus estrogens for human biology is best illustrated by disease states, both deficiency and excess which might be caused by genetic disorders.Aim: A novel deletion-insertion mutation spanning from intron 10 to the 3...

hrp0084p2-314 | DSD | ESPE2015

Pubertal Virilization in Two Unrelated XY Teenagers with Female Phenotype due to NR5A1/SF-1 Gene Mutation

Philibert Pascal , Fenichel Patrick , Dewailly Didier , Audran Francoise , Fauconnet-Servant Nadege , Paris Francoise , Sultan Charles

Background: Pubertal virilization in a 46,XY DSD patient is generally due to partial androgen insensitivity, 5-alpha-reductase deficiency, or 17-ketoreductase deficiency. Recently, reports have identified virilization signs associated with NR5A1/SF-1 gene mutations.Cases presentation and method: We present two unrelated cases of pubertal virilization due to NR5A1/SF-1 gene mutation. Both were suspected to be primarily affected by 5-alph...

hrp0084p2-315 | DSD | ESPE2015

Chimerism in a Teenager with Ovotesticular Disorder of Sexual Development

Buzduga Mihaela , Meyrat Blaise , Typaldou Sofia Anna , Estremadoyro Vanina , Maestre Leonor Alamo , Dwyer Andrew , Pitteloud Nelly , Phan-Hug Franziska

Background: Chimerism is the phenomenon of two or more genetically distinct cell lines (originating from different zygotes) in the same individual. In situations when the sex of the fertilised eggs is disparate, it can lead to intersex phenotypes.Objective and hypotheses: We report a case of ovotesticular disorder of sexual development with chimerism resulting from a twin pregnancy (not involving assisted reproductive technologies).<p class="abstext"...

hrp0084p2-316 | DSD | ESPE2015

Partial Androgen Insensitivity: Syndrome or Symptoms?

Charles Sultan , Pascal Philibert , Nicolas Kalfa , Laurent Maimoun , Francoise Audran , Nadege Servant , Laura Gaspari , Francoise Paris

Background: Partial androgen insensitivity syndrome (PAIS) covers a large spectrum of phenotypes, with the common denominator being insufficient virilisation of the external genitalia in an XY child with normal testosterone (T) production. Genetic diagnosis of PAIS is based on the identification of an androgen receptor (AR) gene mutation.Aim: The aim of this work was to determine whether the PAIS-like phenotype is associated with other gene mutations.</p...

hrp0084p2-317 | DSD | ESPE2015

Next-Generation Sequencing as a Rapid Molecular Diagnosis in Patients with 46,XY Disorder of Sex Development

Ozen Samim , Onay Huseyin , Atik Tahir , Solmaz Asli Ece , Goksen Damla , Ozkinay Ferda , Darcan Sukran

Background: 46,XY DSD occurs as a result of testicular developmental disorders, defect in androgen synthesis or action. Nowadays, the diagnosis of DSD is quite costly and it takes a considerable amount of time due to lengthy hormonal and genetic analysis.Objective and hypotheses: The use of targeted next-generation sequencing of all known genes associated with 46 XY DSD for a fast molecular genetic diagnosis in patients in whom underlying defect of DSD w...

hrp0084p2-318 | DSD | ESPE2015

When, if Ever, Should the Müllerian Remnants be Removed from Subjects with Mixed Gonadal Dysgenesis Raised as Males?

Segev-Becker Anat , Meisler Sarah , Eyal Ori , Oren Asaf , Davidov Anita Schachter , Weintrob Naomi

Background: Mixed gonadal dysgenesis (MGD) is the second most frequent cause of XY disorders of sex development (DSD). Genotype is either X/XY or XY, while the phenotype ranges from partial to complete gonadal dysgenesis, and from female to male external genitalia. Müllerian remnants are present in these patients because of insufficient or untimely foetal secretion of Müllerian inhibiting factor (MIF).Aim: To assess the therapeutic policy of ph...

hrp0084p2-319 | DSD | ESPE2015

Gonadotropin Surge During the Early Postnatal Activation Period in 46,XX Testicular/Ovotesticular Disorder of Sex Development Patients

Costanzo Mariana , Guercio Gabriela , Marino Roxana , Ramirez Pablo , Garrido Natalia Perez , Vaiani Elisa , Berensztein Esperanza , Lazzati Juan Manuel , Maceiras Mercedes , Rivarola Marco A , Belgorosky Alicia

Background: During the 1st months of postnatal life serum luteinizing hormone (LH) levels in girls are lower than in boys. The mechanism of this sex difference is not known. It has been proposed that foetal or perinatal androgenic steroids have an effect on the control of LH secretion.Objective and hypotheses: To study the possible influence of high levels of androgens on serum gonadotropins during the 1st months of life in a cohort of nine 46,XX testicu...

hrp0084p2-320 | DSD | ESPE2015

The Evaluation of AR and SRD5A2 Gene Mutations in 87 Patients with 46, XY DSD Children in Turkey

Akcan Nese , Toksoy Guven , Uyguner Oya , Saka Nurcin , Altunoglu Umut , Abali Zehra Yavas , Genens Mikayir , Poyrazoglu Sukran , Bas Firdevs , Bundak Ruveyde , Kayserili Hulya , Darendeliler Feyza

Background: Main diagnosis of 46,XY disorders of sex development (DSD) with normal testosterone secretion Androgen insensivity sydrome (AIS) or 5α-reductase deficiency (5α-RD). In prepubertal period, AIS and 5α-RD present indistinguishable phenotypes that necessitate the molecular analyses for the definitive diagnosis.Objective and hypotheses: Clinical, hormonal and genetic investigation of 46,XY DSD patients who considered as PAIS or 5&#9...

hrp0084p2-321 | DSD | ESPE2015

Familial Mutation of NR5A1/SF-1 Gene Associated with DSD and Spleen Agenesis: A New Syndrome?

Philibert Pascal , Poulat Francis , Audran Francoise , Cartigny Maryse , Paris Francoise , Sultan Charles , Manouvrier-Hanu Sylvie

Background: A recent report (JCI, 2014) described a new homozygous NR5A1/SF-1 mutation in a patient with XY DSD and spleen agenesis. To date, no other data have confirmed this association, raising the hypothesis of fortuity.Case presentation and method: We had the opportunity to study an adolescent girl referred for virilisation during puberty. She presented voice deepening and clitoral hypertrophy. Biological investigations showed high plasma testostero...

hrp0084p2-322 | DSD | ESPE2015

Clinical Spectrum of 45,X/46,XY Mosaicism and Variants in Children

Jung Hae Woon , Kim Hwa Young , Lee Gyung Min , Kim So Youn , Jeong Kyung A , Choi Keun Hee , Lee Jieun , Lee Young Ah , Shin Choong Ho , Yang Sei Won

Background: The phenotypic manifestations in the 45,X/46,XY karyotype is diverse and there are challenges in management due to this diversity.Objective and hypotheses: The aim of this study was to describe the clinical spectrum of 45,X/46,XY mosaicism and variants diagnosed in childhood.Method: A retrospective review of 20 patients with 45,X/46,XY (n=7) and its variants ((45,X/46,X,der(Y) (n=12)) and 46,X,der(X),t...

hrp0084p2-323 | DSD | ESPE2015

Chromosomal Variations in Children and Adolescents with Gender Dysphoria: Is Routine Karyotyping Indicated?

Goedhart Claire , Brain Caroline , Viner Russell M , Alvi Sabah , Mushtaq Talat , Walker Jenny , Carmichael Polly , Butler Gary

Background: Chromosome analysis is always indicated in disorders of sex development (DSD), but the need for karyotyping in gender dysphoria (GD) is less clear.Aims and objectives: We therefore aimed to review the place of routine chromosome analysis in the management of GD in children and adolescents.Patients and methods: 490 children and adolescents with GD have been referred to the two endocrine clinics forming part of the joint ...

hrp0084p2-324 | DSD | ESPE2015

DSD 46,XY and Serum Steroid Profile Ambiguity due to Combined 17-Beta Hydroxysteroid Dehydrogenase/21-Hydroxylase Deficiencies

Kuznetsova Elena , Ioutsi Vitaliy , Kolodkina Anna , Kalinchenko Natalia , Tiulpakov Anatoly

Background: An accurate and comprehensive assessment of steroid hormones is pivotal for differential diagnosis of disorders of sex development (DSD) 46,XY, a part of which may be due to defects of testosterone biosynthesis.Objective and hypotheses: To describe and characterise a case of DSD 46,XY presented with unusual serum steroid profile.Method: Serum steroid hormones were analysed by liquid chromatography-tandem mass spectromet...

hrp0084p2-325 | DSD | ESPE2015

Frequency of Cryptorchidism and Age at Operation in Helsinki Area between 2004 and 2014

Kohva Ella , Miettinen Paivi , Taskinen Seppo , Raivio Taneli

Background: Cryptorchidism is a risk factor for testicular cancer and poor semen quality. The incidence of cryptorchidism has been lower in Finland than in the other Nordic countries.Objective and hypotheses: We focused to investigate the recent trends in the incidence of undescended testes in the Helsinki area. In addition, we evaluated the age at orchidopexy before and after the release of the Nordic consensus in 2007 recommending operation between 6 a...

hrp0084p2-326 | DSD | ESPE2015

Prevalence of Partial Androgen Insensitivity Syndrome in 3 Cohorts of 46,XY Children Presenting with Isolated Hypospadias, Isolated Micropenis or Isolated Persistent Pubertal Gynecomastia

Francoise Paris , Pascal Philibert , Laura Gaspari , Francoise Audran , Nicolas Kalfa , Charles Sultan

Background: The clinical diagnosis of partial androgen insensitivity syndrome (PAIS) should be systematically considered for all 46,XY newborns/infants with undervirilisation contrasting with normal/elevated plasma testosterone levels. Confirmation of PAIS is based on the identification of an androgen receptor (AR) gene mutation.Aim: This work was undertaken to determine whether the minor forms of undervirilisation such as isolated hypospadias, isolated ...

hrp0084p2-327 | DSD | ESPE2015

A Novel Mutation of Anti-Mullerian Hormone Receptor Gene in a Male with Persistent Mullerian Duct Syndrome

Elias-Assad Ghadir , Elias Marwan , Pressman Asher , Tenenbaum-Rakover Yardena

Background: Persistent Mullerian duct syndrome (PMDS) is a rare genetic disorder of internal male sexual development defined as a lack of regression of Mullerian derivatives in an otherwise normally virilized XY male. Approximately 85% of the cases are caused by mutations of the Anti-Mullerian hormone (AMH) or its’ receptor (AMHR-II) genes. In the current study, we report a novel homozygous mutation in the AMHR-II gene in a patient with PMDS and discuss the dilemma of the...