ESPE Abstracts (2018) 89 P-P2-207

Clinical and Preliminary Molecular Description of a Cohort of Patients with Growth Retardation due to Severe Primary IGF1 Deficiency (GROWPATI Study)

Athanasia Stoupaa,b, Magali Viauda,c, Isabelle Flechtnera, Graziella Pintoa, Dinane Samara-Boustania,c, Caroline Thalassinosa, Laura Gabriela González Briceñoa, Jacques Beltranda,b,d, Irène Netchinee, Frédéric Brioudee, Marie Legendref, Serge Amselemf & Michel Polaka,b,c,d

aPaediatric Endocrinology, Diabetology and Gynecology Department, Necker Children’s University Hospital, Paris, France; bINSERM U1163, IMAGINE Institute Affiliate and U1016, Cochin Institute, Paris, France; cCentre de Référence des Maladies Endocriniennes Rares de la Croissance et du Développement (CMERCD), Paris, France; dParis Descartes University, Paris, France; eSorbonne Université, INSERM UMR S938, Centre de Recherche Saint-Antoine, Trousseau Hospital, Paris, France; fSorbonne Université, Université Pierre et Marie Curie, Université Paris 06, INSERM UMR S933, Trousseau Hospital, Genetics department, Paris, France

Background: Severe primary insulin-growth factor-1 (IGF1) deficiency (SPIGF1D) is a rare cause of growth retardation. Diagnostic criteria include age- and sex-dependent low basal IGF1 levels (<2.5th percentile), height ≤ −3SDS, absence of growth hormone (GH) deficiency and of any secondary causes of growth failure.

Objectives: Phenotypic description, follow-up and molecular studies in a cohort of patients diagnosed with growth failure due to SPIGF1D.

Methods: The historical study cohort was composed by patients (n=2546) referred to Pediatric Endocrinology Department of Necker Children’s University Hospital, in Paris, France between 2004 and 2009 (Teissier et al., EJE, 2014). A group of patients (n=30) had been identified with SPIGF1D. We extended this cohort and further included 15 more patients with SPIFGD. Patients were followed up to December 2017 and data is presented concerning growth rate, puberty, final height, when available. Molecular studies were performed based on candidate gene approach by Sanger sequencing from patients’ DNA (blood samples).

Results: From our current cohort of 45 patients with SPIGF1D, 27 patients were born small for gestational age (SGA) and 18 patients were classified with idiopathic short stature (ISS). At inclusion all patients were prepubertal. Four patients were diagnosed with constitutional bone disease (skeletal dysplasia). One patient was diagnosed with hypochondroplasia due to FGFR3 mutation. Laron syndrome was diagnosed in a girl with severe growth failure (height: −9SDS). A heterozygous mutation in GHR was identified in two unrelated children. Noonan syndrome was diagnosed in one patient, Silver-Russell syndrome in another. GH treatment was initiated for 27 patients, in a context of SGA or ISS. Increlex® (recombinant human IGF1, rhIGF1) was initiated for two patients, without any adverse effects observed so far. All patients have had a normal puberty onset, on-going for most of them. Three patients (two males, one female) have achieved their final height. Genetic studies are ongoing for the remaining patients.

Conclusion: Our study provides a detailed clinical description of a well-characterised cohort of patients with SPIGF1D and confirms the heterogeneous spectrum of the disease. Long-term follow-up, especially for final height is necessary. On-going genetic studies will provide more insights in the understanding of SPIGF1D.