ESPE Abstracts

Background: GLI2 is a transcription factor in Sonic Hedgehog signaling and implicated in ventral forebrain and pituitary development. GLI2 mutations were reported not only in patients with holoprosencephaly but also in patients with pituitary hormone deficiencies without holoprosencephaly. Other phenotypes of GLI2 mutations are midline facial defects, cleft hands and feet, and polydactyly. We report two patients with combined pituitary hormone deficiency, carrying GLI2 mutations.

Objective and hypotheses: Reporting two cases of combined pituitary hormone deficiency proven to have novel mutations of GLI2.

Method: Genomic DNA was extracted from the patients, and 11 genes related to congenital hypopituitalism were screened on Miseq next generation sequencer.

Case 1: The patient was born full term by vaginal delivery without fetal distress. He had cleft lip and palate, micropenis, cryptorchidism, GH, TSH, ACTH, LH, FSH and antidiuretic hormone deficiencies. A brain MRI showed a pituitary aplasia and an ectopic posterior lobe.

Case 2: The patient was born full term by vaginal delivery without fetal distress. He had micropenis, cryptorchidism, GH, TSH, ACTH, LH and FSH deficiencies. A brain MRI showed a pituitary hypoplasia and an ectopic posterior lobe.

Results: We identified heterozygous GLI2 mutations: c.3544 C>T, p.Gln1182*(Case1) and c.3076dupC, p.Ser1025fs(Case2).

Conclusion: The phenotypes of GLI2 mutations are variable. Case 1 is the first case who has antidiuretic hormone deficiency with an ectopic posterior lobe in patients carrying GLI2 mutations. Like case 2, in patients with only pituitary hormone deficiency, GLI2 mutations may be identified more than expected.