ESPE Abstracts (2019) 92 P1-80

Clinical Characteristics, Puberty Pattern and Adult or Near-adult-height Data in a Group of Patients with Growth Failure due to Severe Primary IGF-1 Deficiency (GROWPATI Study)

Athanasia Stoupa1,2, Christine Lorraud1, Isabelle Flechtner1, Magali Viaud1,3, Graziella Pinto1, Dinane Samara-Boustani1,3, Caroline Thalassinos1, Frédéric Brioude4, Irène Netchine4, Serge Amselem5, Marie Legendre5, Michel Polak1,2,3,6


1Paediatric Endocrinology, Diabetology and Gynaecology Department, Necker Children's University Hospital, Paris, France. 2Institut Imagine Affiliate, INSERM U1163 and U1016,Institut Cochin, Paris, France. 3Centre de référence des maladies endocriniennes rares de la croissance et du développement (CMERCD), Paris, France. 4Sorbonne Université, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Trousseau Hospital, Paris, France. 5Sorbonne Université, INSERM UMR_S933, Genetics Department, Trousseau Hospital, Paris, France. 6Paris Descartes University, Paris, France


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

Objectives: Description of pubertal onset and growth spurt, data on adult or near-adult-height in a subgroup of patients diagnosed with growth retardation due to SPIGF1D.

Methods: Thirty patients (Male,M /Female,F:17/13) have been identified with SPIGF1D (historical study cohort) out of 2546 patients referred for growth failure to Paediatric Endocrinology Department of Necker Children's University Hospital, in Paris between 2004 and 2009 (Teissier et al, EJE, 2014). We extended this cohort including 19 more patients with SPIFGD characteristics (new cohort) among patients with growth retardation between 2016-2019. Data are presented for a subgroup of patients from both cohorts (n=19,11M/8F) concerning puberty (Tanner stage, menarche) and adult height, if available. Adult height was defined as last height velocity <1cm/year.

Results: From the current cohort of 49 patients with SPIGF1D, 29 patients were born small for gestational age (SGA). Genetic results available so far outline the heterogeneity of the disease: constitutional bone disease (skeletal dysplasia, n=4), hypochondroplasia (n=1), Laron syndrome (n=1), heterozygous GHR mutations (n=2), Noonan syndrome (n=1), Silver-Russell syndrome (n=2). Genetic studies are ongoing for the rest of the cohort. At inclusion all patients were pubertal stage 1. Mean actual age of patients in the historical and new cohort is 17 and 9.5 years respectively. Data are presented for the subgroup of 19 patients from both cohorts. Pubertal onset was normal with a mean age for Tanner stage 2 of 12.5 years for boys (n=11) and 12 years for girls (n=8). Mean age of menarche was 13.6 years with regular menstrual cycles. Two boys had advanced evolutive central puberty, treated by GnRH agonist. Adult height/near-adult height was available for 5 boys, mean (SD): -2.2 SDS(0.3) and 4 girls, -2 SDS(1), except a female patient with Laron syndrome (final height:128.5cm). Predicted adult heights for boys and girls with available final heights were -1.5 SDS(0.4) and -1.8 SDS(0.6), respectively. These patients have been treated by growth hormone or, for Laron syndrome, by Increlex®(recombinant human IGF1).

Conclusion: Final heights in our patients were below predicted adult heights, and height velocity during puberty varied. Long-term follow-up and genetic investigations are necessary for providing more insights in the SPIF1D.