ESPE Abstracts

Background: Pituitary stalk interruption syndrome is a rare disorder characterized by an absent or ectopic posterior pituitary, anterior pituitary hypoplasia and an interrupted pituitary stalk. In some cases, a variety of additional congenital defects may be present. A genetic cause is identified in only around 5% of all cases.

Case presentation: A 13-year-old male presented to the pediatric endocrinology clinic because of short stature. The patient was diagnosed as an infant with a bicuspid aortic valve and vascular ring, as well as right kidney dysplasia with severe vesicoureteral reflux for which he underwent nephrectomy. At presentation, he had a height of 139 cm (<3rd percentile), a weight of 41 kg (10th - 25th percentile), absence of pubic and axillary hair, with a testicular size between 8 and 10 ml. The patient underwent laboratory testing which revealed growth hormone deficiency (IGF-1 41ng/ml, abnormal clonidine, and glucagon stimulation test), and central hypothyroidism (FT4 0.88 ng/ml, TSH 3.64 μIU/ml). Bone age was consistent with 11 years. Pituitary MRI showed absence of the pituitary stalk with hypoplasia of its anterior lobe and ectopic neurohypophysis, findings consistent with pituitary stalk interruption syndrome (PSIS). Various morphological abnormalities of the cervical spine were also detected. Replacement therapy with growth hormone and thyroxine was initiated. As part of the investigation of the patient's multiple pathologies, whole exome sequencing (WES) study was performed, detecting a c.1343-56G>C mutation in intron 10 of the ROBO1 gene in heterozygosity. No other significant variants were detected.

Discussion: PSIS is a rare cause of hypopituitarism. Mutations of the ROBO1 gene have recently been associated with this condition, as well as with renal agenesis or dysgenesis and congenital heart defects. We report a previously undescribed variant of the ROBO1 gene in a patient that had PSIS, heart and renal defects, although pathogenicity of this intronic variant remains unknown.