Ectopic Posterior Pituitary, Polydactyly, Midfacial Hypoplasia and Multiple Pituitary Hormone Deficiency due to a Novel Heterozygous IVS11-2A>C(c.1957-2A>C) Mutation in the GLI2 Gene

J Clin Res Pediatr Endocrinol. 2020 Sep 2;12(3):319-328. doi: 10.4274/jcrpe.galenos.2019.2019.0142. Epub 2019 Nov 29.


A novel heterozygous IVS11-2A>C(c.1957-2A>C) mutation in the GLI2 gene is reported. There was an extremely distinct phenotypical expression in two siblings and their father. The index case was a boy who developed cholestasis and hypoglycaemia in the neonatal period. He had bilateral postaxial polydactyly, mid-facial hypoplasia, high palatal arch, micropenis, and bilateral cryptorchidism. Laboratory examination revealed a diagnosis of multiple pituitary hormone deficiency. There was severe anterior pituitary hypoplasia, absent pituitary stalk and ectopic posterior pituitary on magnetic resonance imaging which suggested pituitary stalk interruption syndrome with no other midline structural abnormality. Molecular genetic analysis revealed a novel heterozygous splicing IVS11-2A>C(c.1957-2A>C) mutation detected in the GLI2 gene. His father and a six-year-old brother with the identical mutation also had unilateral postaxial polydactyly and mid-facial hypoplasia although there was no pituitary hormone deficiency. This novel heterozygous GLI2 mutation detected appears to present with an extremely variable clinical phenotype, even in related individuals with an identical mutation, suggesting incomplete penetrance of this GLI2 mutation.

Keywords: Growth hormone deficiency; polydactyly; GLI2 mutations; multiple pituitary hormone deficiency.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Adult
  • Brain Diseases / complications
  • Brain Diseases / diagnosis
  • Brain Diseases / genetics
  • Child
  • Choristoma / complications
  • Choristoma / genetics
  • DNA Mutational Analysis
  • Facial Asymmetry / complications
  • Facial Asymmetry / diagnosis
  • Facial Asymmetry / genetics
  • Fathers
  • Fingers / abnormalities
  • Heterozygote
  • Humans
  • Hypopituitarism / complications
  • Hypopituitarism / diagnosis
  • Hypopituitarism / genetics*
  • Infant
  • Male
  • Mutation
  • Nuclear Proteins / genetics*
  • Pedigree
  • Pituitary Gland, Posterior / abnormalities
  • Pituitary Gland, Posterior / pathology
  • Polydactyly / complications
  • Polydactyly / diagnosis
  • Polydactyly / genetics
  • Sequence Inversion
  • Siblings
  • Toes / abnormalities
  • Zinc Finger Protein Gli2 / genetics*


  • GLI2 protein, human
  • Nuclear Proteins
  • Zinc Finger Protein Gli2

Supplementary concepts

  • Combined Pituitary Hormone Deficiency
  • Polydactyly, Postaxial