A Child with Non-Growth Hormone-Deficient Short Stature with Chromosome 2 Deletion of 2q35-36.1: A Case Report and Literature Review of Haploinsufficiency of Epha4 Gene

Abstract Non-growth hormone-deficient short stature is a group of growth developmental disorders with complex pathophysiological mechanisms involving multiple pathways, including abnormalities in the growth hormone/insulin-like growth factor 1 signal pathway. We report a 4-year-old girl with severe growth and developmental delay: her height was 91 cm (<–3 standard deviation [SD]), and her growth rate was 3 to 4 cm/year (<–2 SD). Growth hormone stimulation tests indicated a normal peak growth hormone level (11.1 μg/L), while insulin-like growth factor-1 levels were reduced (7.98 nmol/L, <–1SD). Whole exome sequencing and copy number variation analysis revealed a 3.19 Mb deletion at 2q35-q36.1 on chromosome 2, encompassing all coding regions of the Epha4 gene. This study suggests an association between Epha4 gene deletion and non-growth hormone-deficient short stature, highlighting the importance of further research on this gene and its related signaling pathways to understand the molecular mechanisms of the disease and potential therapeutic approaches.