Endocrine Abstracts

Background: Haploinsufficiency of the GATA3 gene located on chromosome 10p15, is well-recognised as the cause of hypoparathyroidism, sensorineural deafness and renal dysgenesis; the HDR syndrome. A number of abnormalities within the GATA3 gene have been identified, with varying phenotypic characteristics. GATA3 is associated with other abnormalities including, abnormalities of Mullerian structures, hypomagnesia, hemimegalenencephaly and diabetes mellitus.

GATA3 is expressed in the embryonic CNS, and has a role to play in the development of hypothalamic 5HT neurons. Knock-down of GATA3 in-vitro is associated with a decrease in expression of genes linked to IGF-signaling, including IGF1, IGF2 and several IGF-binding proteins. Within the anterior pituitary gland, GATA factors have been shown to increase glycoprotein α-subunit gene promoter activity (relating to thyrotroph and gondotroph function) and GATA2-deficient mice exhibit elevated levels of GATA3 transcripts in the pituitary gland, suggesting that GATA3 can compensate for GATA2. However, to date GATA3 mutations in humans have not been reported in conjunction with pituitary dysfunction.

Report: We report the case of a female child who initially presented in the neonatal period with bilateral sensory neural deafness. At eight months of age she was diagnosed with hydrocephalus secondary to a Chiari 1 malformation, which required management with a third ventriculostomy. Subsequently she developed persistent proteinuria and haematuria, partial diabetes insipidus and growth hormone deficiency. Cranial MRI demonstrated a small anterior pituitary, an ectopic posterior pituitary and abnormalities of the cochlea.

CGH array demonstrated interstitial deletion on the short arm of chromosome 10 with breakpoints within p14. The deletion was approximately 7 Kb in size and contained part of the GATA3 gene.

Conclusion: This case demonstrates a previously unreported clinical association between GATA3 and structural abnormalities of the pituitary presenting as diabetes insipidus and growth hormone deficiency. Further work is required to investigate this association.