Life-threatening cardiac episode in a Polish patient carrying contiguous gene microdeletion of the TBX5 and the TBX3 genes

摘要

Holt–Oram syndrome (HOS) features radial ray hypoplasia, heart defect and cardiac conduction impairment. Ulnar-mammary syndrome (UMS) characterizes congenital defects of the ulnar side of the upper limbs, underdevelopment of apocrine glands including hypoplasia and the dysfunction of mammary glands, hypogonadism and obesity. Inheritance of both conditions is autosomal dominant, mutations or deletions are found in the TBX5 and TBX3 gene, respectively. The Polish patient presented short stature, obesity, congenital malformation of the radial and ulnar side of the upper limbs, heart block, hypogonadism and dysmorphic features. At the age of 13 years he lost consciousness developing respiratory insufficiency caused by bradycardia in the course of sudden atrioventricular third degree heart block requiring immediate implantation of pace maker-defibrillator device. Microdeletion of the 12q24.21 was identified using array CGH method. This region includes contiguous genes the TBX5, TBX3, and part of RBM19. The patient initially diagnosed as having HOS, was found to present the UMS features as well. Array CGH method should be applied in patients suspected of HOS or UMS, especially when sequencing of TBX5 or TBX3 genes fails to identify causative mutation.