Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

Abstract

Benign hereditary chorea (BHC) is a rare genetically heterogeneous movement disorder, in which conventional neuroimaging has been reported as normal in most cases. Cystic pituitary abnormalities and features of empty sella have been described in only 7 patients with BHC to date. We present 4 patients from 2 families with a BHC phenotype, 3 of whom underwent targeted pituitary MR imaging and genetic testing. All four patients in the two families displayed a classic BHC phenotype. The targeted pituitary MR imaging demonstrated abnormal pituitary sella morphology. Genetic testing was performed in three patients, and showed mutations causing BHC in three of the patients, as well as identifying a novel nonsense mutation of the TITF1/NKX2-1 gene in one of the patients. The presence of the abnormal pituitary sella in two affected members of the same family supports the hypothesis that this sign is a distinct feature of the BHC phenotype spectrum due to mutations in the TITF1 gene. Interestingly, these abnormalities seem to develop in adult life and are progressive. They occur in at least 26% of patients affected with Brain-lung-thyroid syndrome. As a part of the management of these patients we recommend to perform follow-up MRI brain with dedicated pituitary imaging also in adult life as the abnormality can occur years after the onset of chorea.

Keywords: Benign hereditary chorea; Brain-lung-thyroid syndrome; NKX2.1; Pituitary cyst; Pituitary gland.

Figure 1:

Non-contrast MRI (panels a–c) of the pituitary gland with sagittal (a) and axial (c) T2-weighted as well as coronal T1-weighted dedicated 3-mm thin-sections from case 1, demonstrating thin rim of pituitary tissue along the anterior and inferior aspects of the enlarged CSF-filled sella turcica. Non-contrast multiplanar reformatted CT images (panels d–f) in the corresponding sagittal (d), coronal (e), and axial (f) planes demonstrating smooth remodelling of the osseous boundaries of the sella turcica with no evidence of bony erosion.

Figure 2:

Non-contrast MRI (panels a–c) of the pituitary gland with sagittal (a) T1-weighted as well as coronal (b) and axial (c) T2-weighted dedicated 3-mm thin-sections from case 2. The imaging demonstrates predominantly dorsal expansion of the intrasellar space (white arrow in panel a) with anterior deviation of the infundibulum and relative flattening of the superior contour of the pituitary gland.

Figure 3:

Non-contrast MRI (panels a–c) of the pituitary gland with sagittal (a) T1-weighted as well as coronal (b) and axial (c) T2-weighted dedicated 3-mm thin-sections from case 3. There is subtle expansion of the anterior recess of the sella to thicker with flattening of the superior contour of the adenohypophysis (white arrows in panels a–c).