Familial combined pituitary hormone deficiency by a mutation in PROP1: 4 of 7 brothers affected

AbstractIntroductionPROP1 (Prophet of POUF1) mutations are the most frequent genetic cause of combined pituitary hormone deficiency, a condition associated with a deficiency or inadequate production of hormones of the anterior pituitary. The PROP1 gene encodes a transcription factor involved in the ontogeny, differentiation and function of somatotrophs, lactotrophs and thyrotrophs. These mutations are characterized by a remarkable clinical variability, including time of onset of hormonal deficiencies, hypophyseal dimensions and secretion of cortisol.Case reportWe describe a family of consanguineous parents (second-degree cousins), composed of 7 siblings, 4 with combined pituitary hormone deficiency. Two brothers, 41 and 45 years of age, had an initial diagnosis of dwarfism at ages 9 and 12 respectively. Subsequently, TSH, FSH/LH and prolactin deficiency was detected in both. The latter was also diagnosed with cortisol deficiency. The two sisters, aged 46 and 50-years-old, were diagnosed with combined pituitary hormone deficiency, namely of GH, TSH, FSH/LH, prolactin and ACTH, since the ages of 15 and 9, respectively. There was no previous family history of combined pituitary hormone deficiency. The genetic study was performed in the 4 brothers, detecting a homozygous mutation in the PROP1 gene (c.301–302delAG).ConclusionThis case reflects the variability of clinical expression and the progressive functional impairment, including pituitary secretion of ACTH, in patients with PROP1 gene mutations