On Tuesday September 7th at 17:00 – 18:00 CET an Endo-ERN webinar about  “Overgrowth syndromes: Beckwith Wiedemann syndrome and other rare conditions” will be given by Frédéric Brioude from Hôpital Armand-Trousseau in France.

Overgrowth syndromes are a heterogeneous group of rare disorders characterized by generalized or segmental excessive growth, that can be associated with other features, including macrocephaly or cognitive impairment. These syndromes are caused by either genetic or epigenetic anomalies affecting factors involved in cell proliferation and/or the regulation of epigenetic markers. Overgrowth syndromes are frequently associated with an increased risk of cancer (embryonic tumours during infancy or carcinomas during adulthood), but with a highly variable prevalence, leading to the establishment of screening programs for tumors for some of these rare diseases.

Among these syndromes, Beckwith Wiedemann syndrome (BWS) is an imprinting disorder, characterized by (among others) macroglossia, abdominal wall defects, visceromegaly and hemihyperplasia. This syndrome is mainly due to epigenetic defects (i.e. loss or gain of methylation) within the 11p15 region. Tumour risk is highly dependant on the subtype of molecular defects; thus, this observation led to international recommendations for tumour screening that are stratified depending on the molecular aetiology. Since this consensus in 2018, new data regarding the prevalence and age of occurrence of tumours in BWS have been published, that might lead to new recommendations in the future.

Despite the syndromes having overlapping clinical features, some specific symptoms make it possible to discriminate between different syndromes, allowing specific molecular explorations. However, next-generation sequencing approaches are used nowadays, increasing the number of patients with an identified molecular defect

On Thursday September 9th at 15:00 – 16:00 CET an Endo-ERN webinar about “Update on the management of 46,XX Ovarian Dysgenesis and Primary Ovarian Insufficiency” will be given by Philippe Touraine from APHP-Pitié Salpêtrière Hospital in France.

Primary (premature) ovarian insufficiency (POI) is defined as a loss of ovarian activity before the age of 40, and is characterized by menstrual disturbances (amenorrhea or oligomenorrhea) with elevated gonadotropins (follicle-stimulating hormone [FSH] ≥ 25 IU/L) and low serum estradiol levels.The incidence of POI is around 1 per 100 women overall, and 1 per 1000 women under the age of 30 years. POI leads to infertility and an increased risk of osteoporosis and cardiovascular disease. Different mechanisms are known to be involved in the pathogenesis of POI: decreased primordial follicular pool at birth, accelerated follicular atresia, or a dysfunction of follicular growth. Several causes of POI have been identified, including autoimmunity or iatrogenic causes like chemotherapy or ovarian surgery. Some authors have also suggested environmental causes. Genetic disorders involved include not only Turner syndrome (4-5% of cases of POI) and FMR1 (Fragile X Mental Retardation type 1) gene premutation (3% to 15% of cases of POI), but also monogenic disorders (syndromic or non syndromic). Around 70% of cases remain unexplained, though some of these cases of idiopathic POI may be linked to genetic abnormalities. In recent years, new genetic screening techniques have identified genetic alterations that may be linked to POI. Many familial studies have identified mutations involved in POI, and a few cohort studies have described variants of candidate genes or copy number variants. The webinar will be the opportunity to discuss the clinical management of POI patients and the different genetic strategies to be proposed.

On Monday June 28th at 17:00 – 18:00 CET an ERN BOND webinar about “EuRR-Bone: what and how?” will be given by Natasha Appelman-Dijkstra and Ana Priego Zurita.