ECEESPE2025 Poster Presentations Growth Axis and Syndromes (91 abstracts)
A genetic cause of tall stature is more often detected in children with familial tall stature compared to non-familial tall stature
Kateřina Gregorová 1 , Lukas Plachy 1 , Petra Dusatkova 1 , Klara Maratova 1 , Julia Martinkova 1 , Jana Drabova 2 , Vit Neuman 1 , Stanislava Kolouskova 1 , Marta Snajderova 1 , Barbora Obermannova 1 , Jan Lebl 1 , Zdenek Sumnik 1 & Stepanka Pruhova 1
1Department of Pediatrics, Motol University Hospital and Second Faculty of Medicine, Department of Pediatrics, Prague, Czech Republic; 22 Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
JOINT3242
Introduction: Tall stature (TS) is usually seen as mainly beneficial but can be associated with severe health risks and specific syndromic conditions. In our previous study, we revealed genetic cause in 34 % of children with familial tall stature (FTS) including the de novo pathogenic variants and autosomal dominant inherited syndromes.
Aims: To elucidate the genetic causes of TS in children with non-FTS (nFTS), to describe their phenotype in detail and to compare the results between patients with nFTS and FTS.
Methods: We enrolled children with nFTS (defined as a height > 2 SD with both parents’ heights < 2 SD) referred to our centre or already followed up at our clinic between 9/2020 and 4/2024. Participants underwent genetic testing through cytogenetic analysis and next-generation sequencing of 786 growth-associated genes. Genetic findings were assessed following the American College of Molecular Genetics and Genomics guidelines. All participants also received standard endocrinological assessments and specialized anthropometric evaluations.
Results: In total, 55 children with nFTS were enrolled. Their median height was +2. 8 SD (IQR 2. 4-3. 2 SD), and their median midparental height was +0. 7 SD (IQR 0. 4-0. 9 SD). Genetic causes of TS were identified in 6/55 (11%) children (causal variant in TGFRB2 and SHOX, 47, XXY [2x], 47, XXX, 48, XXXX). Additionally, in 6 children, who showed dysmorphic features suggestive of connective tissue disorder, we found interesting variants of unknown significance in genes associated with connective tissue (MATN3, COL2A1, COL11A1, COL1A1, COL1A2, COL6A3 and ADAMTSL4) that are however not associated with TS yet. In comparison to the FTS cohort, the genetic cause of TS was significantly more common in FTS (32%) than in nFTS (11%). The presence of dysmorphic features was observed in 71% of children with FTS compared to 78% of children with nFTS.
Conclusion: Genetic causes of TS are more frequently found in children with FTS compared to those with nFTS. As the FTS is the clinical diagnosis mostly without indication for further investigation, children with FTS are at higher risk of being underdiagnosed. Although several variants were classified as variants of unknown significance based on current knowledge, primary connective tissue disorders may play a more important role in the aetiology of TS than previously expected.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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