Abstract
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.
Highlights
Holt–Oram syndrome (HOS, OMIM 142900) is a genetic condition characterized by radial ray hypoplasia and congenital heart defect often associated with progressive arrhythmias and dysmorphic features (Holt and Oram 1960; Harris and Osborne 1966)
The syndrome is usually caused by point mutations or intragenic deletions of the TBX5 gene, in rare cases it results from larger deletions encompassing the entire TBX5 coding sequence (Basson et al 1997; Gruenauer-Kloevekorn and Froster 2003; NewburyEcob et al 1996)
We describe a Polish proband presenting the overlapping phenotype of HOS and Ulnarmammary syndrome (UMS), resulting from contiguous microdeletion comprising the TBX5, TBX3 and a part of RBM19 genes, located on chromosome 12q24.21
Summary
Holt–Oram syndrome (HOS, OMIM 142900) is a genetic condition characterized by radial ray hypoplasia and congenital heart defect often associated with progressive arrhythmias and dysmorphic features (Holt and Oram 1960; Harris and Osborne 1966). Ulnar-mammary syndrome (UMS, OMIM 181450) is a congenital malformation syndrome Case description This boy was born at term, by Caesarean section due to foetal bradycardia. The early psychomotor and intellectual development was normal and the boy attended public school His parents, younger sister and two maternal half-siblings are healthy. Younger sister and two maternal half-siblings are healthy He was referred to our Institute at the age of 14 years due to dysmorphic features, congenital malformations of the upper limbs, heart block, and hypogonadism. The boy presented with short stature 145 cm (
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