ESPE Abstracts

Hypopituitarism refers to the insufficient secretion of one or more pituitary hormones. If default is present at the time of birth is called congenital hypopituitarism (CH). Causes of this are perinatal pathology and genetic alterations. The clinical presentation is heterogeneous. The diagnosis is made by clinical suspicion supported by hormonal determinations, brain imaging test (MRI) searching of structural defects and genetic study. The development of the pituitary gland is a complex process regulated by specific transcription factors. Mutations in precursor genes result in different degrees of hypopituitarism, which may be associated genes are PROP1, POU1F1, LHX3, LHX4 and HESX1. In recent years, due to advances in genetic sequencing techniques, a large number of genes associated with etiology of CH have been known. The type of inheritance shows great variability. We present the cases of two pairs of siblings affected by CH of genetic etiology.

Case 1: 24-month-old-male patient, under study for short stature, an imaging test (MRI) is performed, in which structural alteration of the pituitary area is observed (pituitary hypoplasia, absence of pituitary stalk and ectopic neurohypophysis). In the genetic study there was a heterozygous pathogenic mutation in the GLI2 gene. His younger brother also shows short stature, the directed study was carried out, with a heterozygous pathogenic mutation of the same gene. The MRI showed the same structural alteration as his brother. The family genetic study revealed that the mother of both is a carrier of the pathogenic mutation.

Case 2: 21-month-old female patient, under study due to short stature and hypoglycemia. She had a history of congenital strabismus. The imaging study shows a structural alteration of the pituitary gland and an disturbance in the gene FOXA2 in the genetic study (heterozygous pathogenic mutation). A study was carried out on his 7-month-old brother with short stature and hypoglycemia, with an alteration in the same gene and the same imaging at pituitary gland. The family genetic study revealed that the father of both is a carrier of the pathogenic mutation. In both cases, the similar clinical presentation in the siblings allowed us to conduct a directed family genetic study of the affected genes. The most appropriate approach to the study of the genetic etiology of CH should be through massive sequencing studies, with caution at interpreting the results and approaching a possible family study and genetic counseling.