ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study provides an in-depth exploration of the genetic underpinnings and clinical phenotypes associated with congenital hypopituitarism (CH) and related disorders. The authors analyse a large cohort (1765 patients) with or at risk of CH from 1563 unrelated families by Sanger, whole exome (WES) or whole genome sequencing (WGS). Genetic variants were identified in 10% of the CH cohort.

CH is characterized by the insufficient production of one or more pituitary hormones. It is often caused by mutations in genes involved in pituitary development and function. This study benefits from its robust sample size of 1765 patients. The authors provide a comprehensive spectrum of genetic variants associated with CH. This large dataset allows the researchers to uncover common and rare mutations, providing a detailed picture of the genetic architecture of the disease. The study goes a step further by relating genetic findings to clinical phenotypes. This phenotypic characterization is key to understanding the heterogeneity of the disease presentation, which varies widely from patient to patient. The paper provides important insights into how different genetic mutations may lead to varying degrees of hypopituitarism, from isolated hormone deficiencies to more complex syndromes involving multiple hormone deficiencies and associated developmental defects. The identification of new genetic variants in known genes also holds potential for future functional studies to understand the key genes involved in pituitary development and disease.

These findings have significant clinical implications. By correlating genetic variants with specific phenotypes, this research aids in improving diagnostic precision for congenital hypopituitarism and related disorders. Early genetic diagnosis can guide personalized treatment plans, such as hormone replacement therapy tailored to the patient’s specific deficiencies. Furthermore, recognizing the genetic cause of a patient’s condition can provide prognostic information and inform counselling for families regarding the likelihood of recurrence in future pregnancies.