hrp0095p1-181 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

Monoallelic variants in Myelin Regulatory Factor (MYRF) associated with 46,XY DSD – two cases and first report of inheritance through parental mosaicism

Kaninde Abhidhamma , Chandran Harish , McCarthy Liam , Ghose Arun , Ellis David , Fulton Piers , Vogt Julie , Igbokwe Rebecca , Jeremy Kirk Jeremy , Mohammed Zainaba , Idkowiak Jan

Background: Haplo-insufficiency of the Myelin-Regulatory Factor (MYRF) gene causes cardiac-urogenital syndrome (CUGS) and Differences in Sexual Development (DSD) in 46,XY and 46,XX (OMIM #618280). The gene product, a transcription factor, is involved in development of Coelomic epithelium derived cells, and likely causative for DSD. To date, only a few MYRF de novo variants are reported in children with DSD and associated CUGS symptoms.<s...

hrp0086p2-p847 | Syndromes: Mechanisms and Management P2 | ESPE2016

Late Presenting Girls with Turner Syndrome can Achieve a Normal Final Height

Sakka Sophia , Shaw Nick , Kirk Jeremy

Background: The diagnosis of turner syndrome (TS) must be included in the differential diagnosis of all girls with short stature. Despite overall earlier diagnosis and treatment there still remain patients with TS who present late with delayed puberty. Although growth hormone (GH) is known to increase final height (FH) in girls with TS, little evidence exists on treatment in late-presenting girls.Objective and hypotheses: To assess the effect of late GH ...

hrp0082p3-d2-967 | Sex Development (1) | ESPE2014

Phenotypic and Genotypic Variability of Patients with 5-α Reductase Type 2 Deficiency

Hu Kun , Krone Nils , Kirk Jeremy

Background: Steroid 5-α reductase type 2 (SRD5A2) deficiency is an rare inherited disorder resulting from mutations in the SRD5A2 gene, causing 46,XY DSD (Disorder of Sex Development). The mutated SRD5A2 enzyme can no longer convert testosterone to dihydrotestosterone, which is needed for virilisation of external genitalia.Objective and hypotheses: To describe the phenotype, investigations and management of SRD5A2 deficiency.<p class="a...

hrp0084fc11.4 | Neuroendocrinology | ESPE2015

Idiopathic Multiple Pituitary Hormone Deficiency (IMPHD): Radiological and Perinatal Factors

Ginige Nimasari , Kirk Jeremy M W , MacPherson Lesley K R

Background: Most cases of multiple pituitary hormone deficiency (MPHD) are acquired and genetic aetiology is rare in the UK. We have investigated whether environmental factors are implicated in ‘idiopathic’ MPHD (IMPHD).Objective and hypotheses: In IMPHD to determine perinatal risk factors and radiological features; to identify the regional epidemiology.Method: Systematic analysis of paediatric IMPHD cases in the UK West ...

hrp0089p1-p220 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P1 | ESPE2018

Pitfalls in the Diagnosis of An Infant with 46,XX DSD with Congenital Adrenal Hyperplasia due to Cytochrome P450 Oxidoreductase Deficiency – the Value of Simultaneous Genetic Analysis to the Diagnosis in DSD

Idkowiak Jan , Mohamed Zainaba , Allen Stephanie , Chandran Harish , McCarthy Liam , Kirk Jeremy , Cole Trevor , Krone Nils

Introduction: Congenital adrenal hyperplasia (CAH) is the underlying diagnosis in most newborns presenting with 46,XX disorders of sex development (DSD). Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of CAH caused by inactivating mutations in the POR gene. POR is a crucial electron donor to all microsomal type 2 P450 cytochromes (CYPs), including 21-hydroxylase (CYP21A2) and 17alpha-hydroxylase (CYP17A1). The hallmark feature of PORD is combined sex-steroid a...

hrp0092rfc14.5 | Adrenals and HP Axis | ESPE2019

Bioactive IGF-I Concentration Compared to Total IGF-I Concentration Before and After 1 Year of High-Dose Growth Hormone in Short Children Born Small for Gestational Age - North European SGA Study (NESGAS)

Beck Jensen Rikke , Gersel Wegmann Mathilde , Thankamony Ajay , Roche Edna , Hoey Hilary , Kirk Jeremy , Ivarsson Sten-A. , Söder Olle , Frystyk Jan , Dunger David B. , Juul Anders

Background: Children born small for gestational age (SGA) exhibit wide variations in the activity of growth hormone (GH)/insulin–like growth factor–I (IGF-I) axis and this heterogeneity may result in supra physiological concentrations of IGF-I during GH treatment. The long-term effects of elevated IGF-I levels has been a matter of concern. We explored the variations in total IGF-I and bioactive IGF-I and the associations with growth and glucose metab...

hrp0089p2-p348 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P2 | ESPE2018

Revisiting the Diagnosis: Next Generation Sequencing (NGS) Identifies Concurrence of PAIS in a Previously Reported Case of Klinefelter Syndrome (47,XXY) with Hypospadias

Mohamed Zainaba , Allen Stephanie , Bounford Kirsten McKay , Idkowiak Jan , Godber Caroline , Chandran Harish , McCarthy Liam , Cole Trevor , Kirk Jeremy , Krone Nils

Background: Klinefelter syndrome (KFS) is a sex chromosomal disorder characterised by hypogonadism, progressive testicular failure, gynaecomastia and learning difficulties. Genital anomalies are rarely observed in KFS. Androgen insensitivity has been previously postulated, but not proven to cause genital ambiguity in KFS. Androgen receptor (AR) gene defects are reported in AIS, but have not been reported in children with KFS with mild hypospadias. We describe a novel ...

hrp0086p1-p604 | Growth P1 | ESPE2016

The Exon3-Deleted Growth Hormone Receptor Gene Polymorphism (d3-GHR) is Associated with Increased Spontaneous Growth and Impaired Insulin Sensitivity in Prepubertal Short SGA Children (NESGAS)

Wegmann Mathilde Gersel , Jensen Rikke Beck , Thankamony Ajay , Kirk Jeremy , Donaldson Malcolm , Ivarsson Sten-A , Soder Olle , Roche Edna , Hoey Hillary , Dunger David B , Juul Anders

Background: A common polymorphism in the growth hormone receptor gene (d3-GHR) was found to be associated with pre- and postnatal growth and GH-induced growth. D3-GHR was associated with glucose metabolism in adults with GHD and acromegaly, but this has not previously been explored in children.Objective and hypotheses: We examined the impact of the GHR-exon-3 deletion on glucose metabolism and anthropometrics in short SGA children before and following 1 ...

hrp0082fc7.1 | Growth promoting therapies | ESPE2014

Genetic Markers of Insulin Resistance are Associated with GH Response in Short SGA Children: the North European SGA Study

Jensen Rikke Beck , Thankamony Ajay , Day Felix , Kirk Jeremy , Donaldson Malcolm , Ivarsson Sten-A , Soder Olle , Roche Edna , Hoey Hilary , Juul Anders , Ong Ken , Dunger David

Background: There is wide heterogeneity in responses to GH treatment in children born small for gestational age (SGA).Objective and Hypotheses: The aim was to explore the impact of genetic markers on glucose metabolism and growth during first year high-dose GH treatment in SGA children.Method: In North European Small for Gestational Age Study (NESGAS) patients received high-dose GH (67 μg/kg per day) the first year. 97 patient...

hrp0089rfc1.4 | Adrenals &amp; HPA Axis | ESPE2018

Mass Spectrometry-Based Assessment of Childhood Androgen Excess in 487 Consecutive Patients Over 5 Years

Idkowiak Jan , Elhassan Yasir S , Mannion Pascoe , Smith Karen , Webster Rachel , Saraff Vrinda , Barrett Timothy G , Shaw Nick J , Krone Nils , Dias Renuka P , Kershaw Melanie , Kirk Jeremy , Krone Ruth E , O'Reilly Michael W , Arlt Wiebke

Background: Androgen excess in childhood is a common clinical presentation and might signify serious pathology. We have recently explored patterns and severity of androgen excess in a large female adult cohort to differentiate common polycystic ovarian syndrome (PCOS) from non-PCOS pathology, including congenital adrenal hyperplasia (CAH), ovarian hyperthecosis and adrenal and ovarian tumours (Elhassan et al., JCE&M 2018). Herein, we undertake a similar approach f...