Horm Metab Res 2019; 51(02): 81-90
DOI: 10.1055/a-0822-3637
Review
© Georg Thieme Verlag KG Stuttgart · New York

Congenital Hypopituitarism: Various Genes, Various Phenotypes

Maria Xatzipsalti
1   Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, “Aghia Sofia” Children's Hospital, Athens, Greece
2   First Department of Pediatrics, “Aglaia Kyriakou” Children's Hospital, Athens, Greece
,
Antonis Voutetakis
1   Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, “Aghia Sofia” Children's Hospital, Athens, Greece
,
Lela Stamoyannou
2   First Department of Pediatrics, “Aglaia Kyriakou” Children's Hospital, Athens, Greece
,
George P. Chrousos
1   Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, “Aghia Sofia” Children's Hospital, Athens, Greece
,
Christina Kanaka-Gantenbein
1   Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, “Aghia Sofia” Children's Hospital, Athens, Greece
› Author Affiliations
Further Information

Publication History

received 27 March 2018

accepted 10 December 2018

Publication Date:
13 February 2019 (online)

Abstract

The ontogenesis and development of the pituitary gland is a highly complex process that depends on a cascade of transcription factors and signaling molecules. Spontaneous mutations and transgenic murine models have demonstrated a role for many of these factors, including HESX1, PROP1, PIT1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, SHH, GLI2, and FGF8 in the etiology of congenital hypopituitarism. Genetic mutations in any of these factors can lead to congenital hypopituitarism, which is characterized by the deficiency in one or more pituitary hormones. The phenotype can be highly variable, consisting of isolated hypopituitarism or more complex disorders. The same phenotype can be attributed to different gene mutations; while a given gene mutation can induce different phenotypes. This review highlights the genetic variations that lead to congenital hypopituitarism and their associated defects. The overall incidence of mutations in known transcription factors in patients with hypopituitarism is low; therefore many gene mutations or even gene- epigenetic interactions have to be unraveled in the future to explain the vast majority of still unclear cases of congenital hypopituitarism.