Ulnar Mammary syndrome and TBX3: expanding the phenotype

Abstract

We present a patient with features of Ulnar Mammary syndrome (UMS) consisting of bilateral ulnar defects, inverted nipples, short stature with associated growth hormone deficiency, and cryptorchidism. Our patient also had a hypoplastic anterior pituitary and an ectopic posterior pituitary gland, ventricular septal defect (VSD), and cardiac conduction defects consistent with Wolff-Parkinson-White (WPW) syndrome. Although TBX3 is known to be expressed in both the developing heart and the pituitary gland, conduction defects and anatomical pituitary abnormalities have not been previously described in UMS. This may, in part, be due to the fact that these features are not actively sought in individuals with UMS. Because these new findings have important clinical implications, we suggest that clinicians caring for individuals with UMS offer brain imaging, growth hormone testing, and cardiac arrhythmia screening. The diagnosis of UMS was confirmed on mutation analysis of TBX3. The mother of the propositus was also found to carry the same mutation, although she did not show the classical features of UMS. Therefore, our report also supports the variable expressivity of UMS within the same family.