Holt-Oram syndrome presenting with failure to thrive due to a hemodynamically significant patent ductus arteriosus: the importance of early cardiac evaluation in infants with radial ray abnormalities.

BACKGROUND: Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder caused by pathogenic variants in the TBX5 gene and characterized by radial ray malformations associated with congenital heart defects and/or cardiac conduction abnormalities. Although atrial and ventricular septal defects are the most common cardiac manifestations, other congenital cardiac lesions may occur. Early recognition of cardiac involvement is essential to prevent complications and improve outcomes.

CASE PRESENTATION: We report the case of an 8-month-old female infant presenting with failure to thrive, feeding difficulties, and mild respiratory distress. She had unilateral radial ray abnormalities, including complete absence of the left thumb and index finger with associated radial, carpal, and humeral hypoplasia. Physical examination revealed bounding peripheral pulses and a continuous machinery murmur. Transthoracic echocardiography demonstrated a large hemodynamically significant patent ductus arteriosus (PDA) with pulmonary hypertension and left-sided volume overload. Computed tomography angiography confirmed the diagnosis and excluded associated great vessel anomalies. Based on the characteristic upper limb abnormalities, congenital heart disease, and sinus bradycardia, a clinical diagnosis of HOS was established. Surgical ligation of the PDA was successfully performed without complications. At 6-month follow-up, the patient showed complete resolution of heart failure symptoms, satisfactory catch-up growth, and normal postoperative cardiac findings.

DISCUSSION: This case expands the recognized cardiac phenotype of HOS by describing a hemodynamically significant PDA presenting with failure to thrive and pulmonary hypertension. It also illustrates that the severity of skeletal abnormalities does not predict the type or severity of associated cardiac disease, emphasizing the need for comprehensive cardiovascular assessment in all infants with radial ray abnormalities.

CONCLUSION: Early recognition of HOS and prompt cardiovascular evaluation are critical for identifying treatable congenital heart defects. Timely intervention, combined with multidisciplinary long-term care, can significantly improve clinical, functional, and developmental outcomes in affected children.