IMPE Abstracts

In patients with 46,XY disorders of sex development (DSD), next-generation sequencing (NGS) analysis leads to an aetiological diagnosis in ~40% of the cases. One contribution of this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. The aim of this work is to report a case of a patient with 46,XY DSD in whom the identification of a novel variant in MYRF led to the detection of a clinica...

Constitutional delay of puberty (CDP) and congenital central hypogonadism (CH) show great overlap in clinical features and in gonadotrophin and testosterone serum concentrations in boys. The gold standard to distinguish both entities relies on the assessment of pubertal stage beyond 18 years of age. The long lasting insufficient FSH activity in boys with congenital CH may result in lower AMH and inhibin B serum concentrations compared with boys with CDP....

The genetic defects underlying hypogonadotrophic hypogonadism (HH) are known in approximately 50% of cases. In normosmic patients, abnormal GnRH production or action may be due to defects in regulatory factors or in the genes encoding GnRH or GnRHR. Although many gene variants have been described in GNRHR (4q13.2), the potential impact of structural alterations of the resulting mutant proteins have not been studied. In this study, we analysed the 3D-structure of the variant Gn...

Human growth is highly dependent on the GH-IGF-I axis. GH binding to GH receptor activates janus kinase 2 (JAK2)-signal transducer and activator of transcription 5b (STAT5b) pathway which stimulates transcription of IGF1, IGFBP3, and IGFALS. Although STAT5b deficiency was established as an autosomal recessive disorder, heterozygous dominant-negative STAT5B variants were reported in patients with less severe growth deficit and milder immune dysfunction. Our aim was to develop a...

Introduction: SOFT syndrome (MIM#614813), denoting Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis, is a rare primordial dwarfism syndrome encompassing severe growth failure of prenatal onset, craniofacial dysmorphism, sparse hair, and digital abnormalities associated with biallelic pathogenic POC1Agene variants. Phenotypic spectrum has recently been expanded to include insulin resistance (IR) and muscle cramps.<p class="abst...

Introduction: Short Stature (SS), defined as height below -2 SD, is a common reason for referral to pediatric endocrinologists. Genetic factors determine ~80% of adult height. Lately, next-generation sequencing (NGS) has led to the discovery of an increasing number of novel monogenic causes for SS.Objective: The aim of this work was to identify the genetic etiology of SS of unknown origin (SSUO) in children.<p class=...

Introduction: Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction, relative macrocephaly and protruding forehead in early life, body asymmetry and feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with an SRS-like phenotype remains without an etiological diagnosis. In the last few years, clinical reports have suggested that single...

Introduction: Haematological malignancies represent the most frequent childhood cancer. Little is known about small ovarian follicle function at diagnosis in girls with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) or non-Hodgkin lymphoma (NHL). AMH is a useful marker of small follicles.Aim: To determine small ovarian follicle status at diagnosis and after 3 months of chemotherapy in girls and adoles...

Introduction: Most paediatric rare diseases have an underlying genetic cause but making a molecular diagnosis is often still a challenge. The incorporation of Next Generation Sequencing (NGS) technologies into research and clinical workflows has improved the diagnosis of these disorders.Objective: To evaluate the process of NGS implementation for the diagnosis of genetic endocrine diseases in a tertiary public paediatric...