Introduction: Holt-Oram syndrome is an autosomal dominant condition, that is caused by a mutation of the TBX5 gene. The diagnosis of Holt-Oram syndrome is essentially clinical; the diagnostic criteria include con-genital heart defects and/or heart conduction disorders and preaxial radial anomalies in at least one upper limb identified by X-ray examination. The purpose of this paper is to highlight the importance of an early diagnostic, to prevent the complications and to identify other risk family members.
Case presentation: We present a case of Holt-Oram syndrome diagnosed in the adult period, with a personal history of preaxial polydactyly operated in infancy, multiple cardiac malformations (atrial septal defect, bicuspid aortic valve, left ventricular non-compaction) and radiologic findings consistent with Holt-Oram syndrome. Family history is negative for Holt-Oram syndrome.
Subjectively, the patient has no symptoms and a nor-mal effort tolerance. Clinically, he has perioral cyanosis, a blood pressure of 110/70 mmHg, a heart rate of 85 bpm and a systolic 2/6 murmur at the apex. The electrocardiogram reveals normal sinus rhythm at 85 bpm, a heart axis of +60°, peaked P waves (P pulmonale) and left ventricular (LV) hypertrophy. The transthoracic echocardiogram shows an ostium secundum atrial septal defect, a thickened mitral valve with moderate mitral regurgitation with an eccentric jet, a mildly dila-ted LV, trabeculations of the LV lateral wall, septal and anterior wall hypokinesis, global LV ejection fraction of 50%. In transesophageal echocardiography, it is noticed that the aortic valve is bicuspid, no mitral valve prolapse aspect being observed; for the diagnosis of the atrial septal defect, a bubble contrast echocardiogram was performed with the detection of left to right shunt by negative contrast effect. The radiographic imaging of the hands showed a delayed bone age, corresponding to a 16 yo patient. Genetic testing by MLPA for TBX5 gene was normal and duplications or deletions in the 9 exons of the TBX5 gene were ruled out. The patient will be tested by sequence analysis in order to detect the pathogenic variant in TBX5.
Conclusions: Holt-Oram syndrome is a pleiotropic di-sorder, the main anatomic regions implicated are the heart and the upper limbs. Because of variable expressivity, the diagnosis is sometimes delayed.