Mutations in NKx2.5 gene explain familial forms of atrial septal defect (ASD) associated with atrioventricular conduction disturbances and unexplained sudden death (SD) but cardiac phenotype has not been described in a large population of patients with NkX2.5 mutations.

all successive patients with mutations in NKx2.5 gene were included, representing the whole population of french NKx2.5 mutated patients.

47 pts carried NkX2.5 gene mutations (24 men, median 25 yo, 0 to 69) (20 unrelated families, 2.5±1.5 mutated subject/family). There was an history of SD in 9 and of pace-maker implantation in 5 families.

ASD was present in 70% (surgically corrected in 67% and percutaneoulsy in 2 pts) and ventricular septal defect in 15%. Conduction disturbances were observed in 82%. 13 pts (27%) developped complete or high degree AV block. AvailableECGs showed PR interval of 219±43ms, QRS duration of 86±15ms and a QTc of 408±27ms. Electrophysiological study was performed in 15 pts (3 had infra hisian and 5 suprahisian block). A pace-maker was implanted in 20 pts (with ICD in 5) and a loop recorder in one. Sustained or nonsustained ventricular tachycardia were observed in 6 pts.

Mean ventricular pacing % was 77±37. Six pts were dependent of the pacemaker. Three patients deceased over the follow-up (2 SD and one endocarditis). 13 pts developed paroxysmal or permanent supraventricular arrhythmias (mainly atrial fibrillation). Five pts displayed dilated cardiomyopathy, 3 had left ventricular (LV) hypertrophy and 4 with features of noncompacted LV. LV ejection fraction was normal except in 2 cases (35%).

carriers of NkX2.5 gene mutations harbor a rich phenotype associating most of the time ASD and/or VSD together with evolutive AV block leading to pace-maker/ICD implantation in a significant part of them. Associated LV cardiomyopathy is less frequent but ventricular arrhythmias appear common and SD may happen.