Experience with patients presenting with the clinical features of Holt-Oram syndrome: a single center retrospective...

Holt-Oram syndrome, also known as atrio-digital syndrome, is a rare autosomal dominant genetic disorder primarily characterized by upper limb malformations and congenital heart defects, associated with mutations in the TBX5 gene. Diagnosis is typically based on clinical presentation, and the prognosis for affected individuals is closely related to the severity of cardiac involvement. Our study aims to highlight some key features of Holt-Oram syndrome to improve the level of clinical diagnosis.

We collected 11 patients with clinical features strongly suggestive of Holt-Oram Syndrome at the First Affiliated Hospital of Tsinghua University from January 2010 to January 2025. These patients exhibited both limb malformations and cardiac abnormalities. We then analyzed the characteristics of their diseases.

The skeletal abnormalities and cardiac defects presented in diverse forms among the 11 patients. Among the congenital heart diseases, atrial septal defect (ASD) was the most common, accounting for 80% of cases. However, some patients presented with severe conditions such as tetralogy of Fallot or Ebstein's anomaly. Regarding upper limb malformations, the most frequent finding was triphalangeal thumb (8/10 patients), but thumb hypoplasia or aplasia and radial bone abnormalities were also observed.

The predominant cardiac structural abnormality in this group of patients was atrial septal defect. Upper limb malformations were predominantly characterized by polydactyly or syndactyly. However, arrhythmias appeared to be mainly supraventricular tachycardia, and upper limb involvement did not seem to show a clear left-sided predominance. The prognosis following cardiac corrective surgery was favorable. Nevertheless, for this condition, emphasis should be placed on prevention.