ESPE Abstracts (2022) 95 P1-100


Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic

Introduction: The diagnosis of growth hormone deficiency (GHD) is complex, involving the combination of auxological, laboratory, and radiological findings. This includes growth hormone (GH) stimulation tests, which are done to confirm the diagnosis. It has been discussed that these tests have low specificity, potentially leading to false positive results. Therefore, children with GHD are regarded as a heterogeneous group with varied causes of short stature. Next-generation sequencing (NGS) methods have the potential to elucidate the genetic aetiology in these patients.

Aims: To search for the genetic background of growth disruption in children with familial short stature (FSS) and diagnosed GHD.

Patients and Methods: From 747 children treated with GH in our center, 64 with FSS (life-minimum height in child and his/her shorter parent <-2 SD) and diagnosed GHD (stimulated GH cut off <10 mg /l in two tests with priming if appropriate) were enrolled to the study. Before treatment with GH, the median height of the study cohort was -3.1 SD (IQR -3.6 to -2.7 SD), their IGF-1 concentration was -1.4 SD (IQR -2.0 to -1.2 SD) and maximum stimulated GH was 6.4 mg /l (IQR 4.8-7.9 mg /L). None of the children had multiple pituitary hormone deficiency or a pathology in the midbrain region on MRI. Patient DNA was analysed by targeted NGS panel containing 398 genes known to influence growth. All the variants with potential clinical significance were evaluated by the American College of Medical Genetics (ACMG) standards.

Results: Causative variants in genes affecting growth were found in 21/63 children. Among them, only two (10%) had a variant in a gene involved in the secretion or function of GH (GHSR and OTX2 genes). Interestingly, 15 (71%) patients had a primary defect in the growth plate (genes ACAN, COL11A1, COL11A2, COL1A2, COL2A1, EXT2, FLNB, FGFR3 [2x], NPR2 [3x], NF1, PTPN11 [2x]), 2 others (10%) had variants in genes impairing IGF-1 action (IGFALS a HGMA2) and two (10%) had syndromic short stature (genes MBTPS2, SALL4).

Conclusion: The genetic findings did not correspond with the diagnosis of GHD in most cases of FSS. The results reopen the question about the reliability of standard methods currently used to diagnose GHD.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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