ESPE Abstracts (2021) 94 P1-43

1Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 2Department for BioMedical Research, University of Bern, Bern, Switzerland; 3Developmental Endocrinology Research Group, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, United Kingdom; 4Office for Rare Conditions, University of Glasgow, Glasgow, United Kingdom; 5Department of Medical and Surgical Sciences, University Hospital S.Orsola-Malpighi, Bologna, Italy; 6Growth and Development Group Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 7University of Health Sciences Turkey, Ankara Dr. Sami Ulus Obstetrics and Pediatrics Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey; 8Department of Paediatric Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 9Division of Paediatric Endocrinology, Department of Paediatrics and Internal Medicine, Ghent University Hospital, Ghent University, Ghent, Belgium; 10Istanbul University, Istanbul Faculty of Medicine, Pediatric Endocrinology Unit, Istanbul, Turkey; 11Southampton Children’s Hospital, University Hospital Southampton, Southampton, United Kingdom; 12Laboratory of Human Molecular Genetics, Center of Molecular Biology and Genetic Engineering (CBMEG)/Unicamp, Sao Paulo, Brazil; 13Ukrainian Center of Endocrine Surgery Endocrine Organs and Tissue Transplantation, MoH of Ukraine, Kiev, Ukraine; 14Interdisciplinary Group for the Study of Sex Determination and Differentiation – GIEDDS and Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas, Sao Paulo, Brazil; 15Marmara University, Department of Pediatric Endocrinology and Diabetes, Pendik, Istanbul, Turkey; 16Erasmus Medical Centre, Sophia Children’s Hospital, Department of Pediatric Endocrinology, Rotterdam, Netherlands; 17Leiden University Medical Centre, Department of Pediatrics, Leiden, Netherlands; 18Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Lübeck, Lübeck, Germany; 19Endocrinology Research Centre, Moscow, Russian Federation; 20Wessex Clinical Genetics Service, University Hospital Southampton, Southampton, United Kingdom; 21Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland; 22Department of Endocrinology, Children’s Hospital of Eastern Switzerland, St.Gallen, Switzerland; 23Division of Pediatric Endocrinology and Diabetology and Children’s Research Centre, University Children’s Hospital, Zürich, Switzerland; 24Biocruces Bizkaia Health Research Institute, CIBERDEM, CIBERER, Barakaldo, Spain; 25Clinical Genetics Department, National Research Center, Cairo, Egypt; 26Pediatric Endocrinology and inborn errors of metabolism, Karolinska University Hospital, Stockholm, Sweden; 27Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; 28Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom; 29University Hospital of Messina, Department of Human Pathology of Adulthood and Childhood, Messina, Italy

Background: Steroidogenic Factor 1 (NR5A1/SF-1) is essential for the development and function of human sex and steroid organs. Variants of SF-1 lead to a broad spectrum of phenotypes including adrenal insufficiency and differences of sex development (DSD), but data on the whole picture of phenotypes in individuals with SF-1 variants are currently lacking. We aim to investigate the phenotype of individuals with SF-1 variants in a large international cohort.

Methods: Individuals with known SF-1 variants were eligible if they have disorders of 46,XX or 46,XY gonadal development, disorders of androgen synthesis/action or non-specific disorders of undervirilization. We excluded 46,XX individuals with disorders of androgen excess or disorders of Müllerian development, and 46,XY individuals with Leydig cell defects or Persistent Müllerian Duct Syndrome. We identified the individuals through the international I-DSD network. Eighteen collaborators entered comprehensive phenotyping data according to the Human Phenotype Ontology project in a RedCap database.

Results: By May 2021, 75 individuals with SF-1 variants participated. They were born between 1964-2018 and had their last follow up between 2009-2021. Forty-eight percent of individuals were assigned as boys and girls, respectively (both 36/75). Only 1% was assigned as “other” (1/75) and 3% had unknown sex assignment (2/75). SF-1 variants were mainly identified by single gene analyses (59%, 44/75), followed by gene panels (25%, 19/75), Next Generation Sequencing (15%, 11/75) and Comparative Genomic Hybridization Array (1%, 1/75). Apart from DSD, 42/75 (56%) SF-1 individuals have organ abnormalities (Table).

Table 1 Description of the phenotype in 42/75 patients with SF-1/NR5A1 variants who have organ abnormalities apart from DSD.
Other endocrine*+--------+--++++---++---++-++-----+++
Connective tissue-----------------------------------------
Head or neck-----------+-------+----+---------+------
Immune system---+----+--------+---------------------
Each column represents one patient.* Treatment with growth hormone, thyroid hormones or insulin. Cells with “+” indicate abnormal, cells with “-” normal, and empty cells unknown function or morphology.

Conclusion and Outlook: More than half of individuals with SF-1 variants had multiple organ abnormalities, with a broad spectrum of phenotypes. Systematic phenotyping together with more comprehensive gene profiling will allow to find patterns in patients with SF-1 variants and to identify likely disease-causing variants in additional genes that might impact the phenotype. Genotype-phenotype patterns will help to evaluate the individual risk for adverse health outcomes and to improve long-term care of individuals with SF-1 variants.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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