Congenital hypopituitarism in children. Molecular-genetic characteristics

In connection with the ambiguity in the interpretation of the results of stimulation tests in congenital hypopituitarism, children need to search for molecular genetic markers of the disease. Molecular genetic analysis in patients with congenital hypopituitarism (genes GH1, GHRH, GHRHR,BTK, GHSR, PROP1, POU1F1, HESX1, LHX3, LHX4, SOX3, SOX2, OTX2, GLI2, ARNT2, ARPC5L, DLK1, DRD2, PAX6, RNPC3, SHH, SPCS2, SPCS3), was carried out by new-generation sequencing (NGS) with “Amplisek” technology. All patients with congenital hypopituitarism, who are in a special registry of Saint Petersburg, were included in this study. A difference in the incidence of mutations in patients with multiple deficiency of adenohypophysis hormones (27.7%) and in patients with isolated growth hormone insufficiency (9.6%) was revealed. The mutation frequency of diagnosis in genes responsible for congenital hypopituitarism in patients of Saint Petersburg were studied. Mutations in genes associated with congenital hypopituitarism were identified in 16.3% of patients with pituitary dwarfism (16 of 98). The most commonly diagnosed mutations are changes in gene PROP1. In carrying out the molecular genetic studies of patients with congenital hypopituitarism is necessary to consider the likelihood of the presence of these rare pathologies such as loss of genes GHSR, ARNT2, BTK. Currently conducting molecular genetic studies in patients with congenital hypopituitarism further predicts development of the disease and, if necessary, adjust the ongoing replacement therapy.