A 40-year-old woman was admitted to the hospital because of first time atrial flutter. During admission an echo was performed and a secundum atrial septum defect (ASD) was identified. She was treated with DC conversion and a transcatheter closure of the ASD was scheduled. She was asked about family history.
Her mother experienced cerebral stroke 10 years ago at the age of 60. Echo screening disclosed an ASD which was treated with surgical closure. She had atrial fibrillation and heart failure with EF35%.
Her brother has a pacemaker which was implanted in his 30s because of 3. degree AV-block. As an infant he was examined because of heart murmur. The echo showed a small ASD with spontaneous closure before the age of 2.
Because of arrhythmias and ASD, three family members were tested for variants in NKX2.5 and TBX5 genes. A pathogenic variant Gly80Arg in TBX5 were identified in all three family members. This variant is associated to Holt-Oram syndrome in other families.
Clinical examination showed no obvious skeletal malformations of the upper extremities. X-ray of hands, arms and shoulders identified a malformation of the scaphoid bone in all three family members suggesting Holt-Oram syndrome.
The patient’s 3 children and her brother’s 3 children were all tested for the TBX5 variant and 2 out of the 6 children had the TBX5 variant. Echo showed ASD in both children and Holter monitoring showed 1. degree AV block in 1 of the 2 children with ASD.