ESPE Abstracts

Background: Twenty-three national healthcare networks for rare diseases were identified in 2014 as part of the French scheme on rare diseases. The rare endocrine disease national healthcare network FIRENDO (www.firendo.fr) includes six centers of reference with complementary fields of expertise certified between 2005 and 2006, 30 centers of competence covering all French regions, 18 research and 37 diagnostic laboratories, 5 national learned...

Background: Germline mutations in SDHB gene are associated with the familial paraganglioma (PGL) syndrome that carries the highest malignant potential. Although penetrance is lower than initially described, lack of effective treatments for metastatic PGLs makes screening essential for early tumour detection, surgical removal and improved outcome. However, no consensus exists in relation to timing and mode of screening.Objective: To assess publis...

Background: Beckwith-Wiedemann syndrome (BWS) characterised by a group of clinical abnormalities (macrosomia, macroglossia, neonatal hypoglycaemia, omphalocoele and umbilical hernia) results from dysregulation of imprinted genes due to mosaic paternal uniparental isodisomy (patUPD) of 11p15.5. Its association with tumours of embryonic origin is well documented and screening guidelines largely aim to detect hepatoblastoma and Wilm’s tumours during the first decade of life....

Background: Gender assignment in children with disorder of sex development (DSD) is a key step in their management and needs detailed assessment. In developing countries, children with DSD are often presented late, due to lack of awareness and social stigmatization, which makes management more challenging.Methodology: Retrospective review of complex DSD cases (karyotyping different from current sex of rearing), presented...

Background: Leydig Cell Hypoplasia (LCH) is a very rare autosomal recessive condition that is manifested by a wide spectrum of phenotypes, ranging from completely female external genitalia to male genitalia. Long-term outcome in these patients is unclear.Objectives: To assess sex assignment, clinical characteristics and long-term outcome of 46,XY LCH cases.Patients and Methods: Thr...

Introduction: The Wilms tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline mutations in WT1 have been classically associated with Denys–Drash (DDS) and Frasier syndrome (FS). Exonic missense mutations in the zinc-finger region are the cause of DDS and mutations affecting the canonic donor KTS splice site of intron 9 are the cause of FS. New phenotypes, as 46,XX testicular DSD...

Introduction: Complex and ordered intracellular signal pathways play a significant role in sex determination in mammals, mediating the balance of gonadal development. A major pathway involved in the regulation of the male development is mitogen-activated protein kinase (MAPK) signaling pathway. To date, mutations of MAP3K1 gene have been found to account for approximately 15%-20% of 46, XY gonadal dysgenesis (46, XY GD)....

Background: Virilization at puberty in girls remains a challenge. Several differential diagnoses must be considered including disorders of sex development (DSD) and tumors.Case Report: We report an 11.5-year-old girl who was referred to our center for progressive cliteromegaly since 6 months. Past medical history was remarkable for prematurity of 36 weeks gestation and for mild ongoing psychomotor delay. At presentation ...

Background: Steroidogenic factor 1 (encoded by the NR5A1gene) is a transcriptional regulator of genes involved in gonadal development and steroidogenesis. Mutations in NR5A1 have been identified among the most frequently genetic causes of disorders of sex development (DSD).Objective: To report the phenotype of 31 patients associated with 17 novel and 9 previously described NR5A1 sequence varian...

Abstract: Steroidogenic factor 1 (SF1)/"nuclear receptor subfamily 5 group A member 1" (NR5A1) is involved in adrenal and gonadal development, steroidogenesis and reproduction. The first patient, published in 1999 presented with a 46,XY difference of sex development (DSD) and adrenal insufficiency. The following year the first female patient with only adrenal insufficiency was described. Since then, heterozygous changes in SF-1/NR5A1 causing 46,XY DSD ...