Holt–Oram syndrome presenting as agenesis of the left pericardium

We report on a case of a 60-year-old man with progressive heart failure, mitral and aortic valve insufficiency and bilateral asymmetrical skeletal upper-limb deformities. Central to the suspicion of Holt–Oram syndrome in this patient was the surgical finding of agenesis of the left pericardium. A Holt–Oram syndrome diagnostic was confirmed through molecular analysis of the TBX5 gene. A new amino acid substitution at position 61 of the TBX5 gene was identified and confirmed the clinical diagnosis of Holt–Oram syndrome. The clinical presentation of the present case broadens the clinical spectrum of Holt–Oram syndrome and point out the importance of Tbx 5 in pericardium development. It is still an unstudied issue whether TBX5 mutations may also be present in other clinical presentations where absence of the pericardium is a feature.