ESPE Abstracts

Background: Cardiofaciocutaneous syndrome (CFCS) is a rare autosomal dominant (AD) condition characterized by cardiac abnormalities, a distinctive craniofacial appearance and short stature. Endocrine manifestations include GH deficiency and precocious puberty. CFCS is part of the RASopathy group including Noonan, LEOPARD, and Costello syndromes. The four associated genes are BRAF (~75%), MAP2K1 and MAP2K2 (~25%), and KRAS (<2%). Most individuals represent new sporadic muta...

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...

Background: Paediatric growth hormone deficiency (PGHD) is treated with daily somatropin (recombinant human growth hormone) injections. High rates of discontinuation and poor adherence to treatment, which are associated with worse growth outcomes, have been documented previously, for example in the US and EU. Discontinuation of somatropin has not yet been evaluated using real-world data in Japan.Objectives: To describe d...

Background: Heterozygous de novo variants in SAMD9 cause the complex multisystem growth disorder, MIRAGE syndrome. Core features are myelodysplasia, infection, restricted growth, adrenal hypoplasia, genital/gonadal phenotypes, and enteropathy. However, the range of additional associations is expanding and includes disrupted placental development, poor post-natal growth, and other endocrine features. Milder phenotypes are also described, such ...

Background: Silver-Russell syndrome (SRS) (mainly secondary to 11p15 molecular disruption) and Temple syndrome (TS) (secondary to 14q32.2 molecular disruption) are imprinting disorders with very close phenotypic (prenatal and postnatal growth retardation, early feeding difficulties, early puberty) and molecular anomalies. Our objective was to describe the clinical overlap between SRS and TS and to extensively study the molecular aspects of patients with 14q32.2 molecular disru...

Introduction: The influence of sex chromosomes and sex hormones on early human brain development is still poorly understood. Expression of Y chromosome genes may influence aspects of brain maturation in the 46,XY fetus, but the contribution of different Y genes is unknown. Furthermore, a marked increase in testicular testosterone biosynthesis/release from the testis occurs at around 8 weeks post conception (wpc) in the 46,XY fetus, but it is unclear whether te...

Background: The presentation of early-onset Primary Ovarian Insufficiency (EO-POI), most often with primary amenorrhea, is at one end of a spectrum spanning 40 years. The aetiology of POI is frequently unclear but next generation sequencing of varied age groups has identified several associated genetic variants. Whether girls with EO-POI are more likely to have a genetic aetiology than those with later presentations remains unknown.<stro...

Background: Recurrent miscarriage (RM) is traditionally described as three or more consecutive pregnancy losses and remains a challenging condition, affecting 1-3% of couples trying to conceive. Although factors such as uterine abnormalities, maternal hypothyroidism and parental balanced translocations are associated with RM, in most situations the aetiology is unknown. The coexistence of RM and live births in many families suggests a potential association wit...

Background: Turner syndrome (TS) affects 1:2,500 females and results from complete or partial loss of one of the X chromosomes. Typical traits associated with TS include short stature, primary ovarian insufficiency (POI), autoimmune diseases, and cardiovascular and endocrine disorders. Long-term follow-up is needed from the time of presentation into adult life. Several genetic mechanisms have been proposed to account for the development of TS-associated featur...

Background: The association of intrauterine growth restriction (IUGR), adrenal insufficiency and gonadal dysgenesis is well recognised. Some children have been reported to develop monosomy 7 and myelodysplasia. However, the genetic basis of this condition was poorly understood.Objective and hypotheses: Our aim was to investigate the genetic basis of eight children with IUGR, adrenal insufficiency and gonadal failure and additional features including seve...