Haploinsufficiency of NKX2-1 in Brain-Lung-Thyroid Syndrome with Additional Multiple Pituitary Dysfunction

Horm Res Paediatr. 2019;92(5):340-344. doi: 10.1159/000503683. Epub 2019 Nov 8.

Abstract

Introduction: Heterozygous mutations or haploinsufficiency of NKX2-1 are associated with the brain-lung-thyroid syndrome incorporating primary hypothyroidism, respiratory distress, and neurological disturbances.

Case presentation: We report a patient presenting in the neonatal period with multiple pituitary hormone deficiency including central hypothyroidism and hypoadrenalism, growth hormone deficiency, undetectable gonadotrophins, and a small anterior pituitary on MRI. CGH microarray revealed haploinsufficiency for NKX2.1 and during subsequent follow-up, she has exhibited the classic triad of brain-lung-thyroid syndrome with undetectable tissue on thyroid ultrasonography. Whilst the role of NKX2-1 is well described in murine pituitary development, this report constitutes the first description of multiple pituitary dysfunction in humans associated with the syndrome and haploinsufficiency NKX2-1.

Conclusion: The report highlights a potential need for pituitary screening in patients with established brain-lung-thyroid syndrome and implicates NKX2.1 in human pituitary disease.

Keywords: Brain-lung-thyroid syndrome; Congenital hypothyroidism; Hypopituitarism; NKX2-1.

Publication types

  • Case Reports

MeSH terms

  • Animals
  • Athetosis / diagnostic imaging
  • Athetosis / genetics*
  • Chorea / diagnostic imaging
  • Chorea / genetics*
  • Congenital Hypothyroidism / diagnostic imaging
  • Congenital Hypothyroidism / genetics*
  • Female
  • Haploinsufficiency*
  • Humans
  • Infant
  • Mice
  • Pituitary Diseases / diagnostic imaging
  • Pituitary Diseases / genetics*
  • Respiratory Distress Syndrome, Newborn / diagnostic imaging
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Thyroid Nuclear Factor 1 / genetics*

Substances

  • NKX2-1 protein, human
  • Thyroid Nuclear Factor 1

Supplementary concepts

  • Choreoathetosis, Hypothyroidism, And Neonatal Respiratory Distress