Makindo Medical Notes

🫀 Holt-Oram syndrome (HOS) is a rare inherited disorder that couples cardiac anomalies (esp. septal defects) with upper limb malformations (e.g., absent radius, thumb abnormalities). 🧬 It follows an autosomal dominant inheritance pattern. Recognising the underlying genetics and clinical features helps guide long-term management and family counseling.

ℹ️ About

• Holt-Oram syndrome is a developmental disorder linking skeletal anomalies of the upper limbs with congenital heart defects.
• Often referred to as the "heart-hand syndrome" due to its characteristic manifestations.

🧬 Etiology

• Caused by mutations in the TBX5 gene, located on chromosome 12q24.
• Mutations at the 5' end → more pronounced cardiac abnormalities.
• Mutations at the 3' end → more prominent skeletal deformities.
• Inheritance: Autosomal dominant with variable expressivity and high penetrance.

🩺 Clinical Features

• Cardiac:
  • Septal defects (ASDs, VSDs).
  • Conduction abnormalities (e.g., heart block, arrhythmias).
  • Cardiomegaly and heart failure in severe cases.
• Skeletal:
  • Absent or hypoplastic thumbs (may appear "fingerized").
  • Absent or hypoplastic radius → only one forearm bone visible.
  • Forearm shortening, phocomelia (rare).
• Other: May present asymmetrically; left-sided involvement more common.

🔍 Investigations

• 📸 X-Ray: Absent/hypoplastic radius or thumb abnormality is a key clue.
• 🫀 Echocardiogram: Detects ASDs, VSDs, or conduction abnormalities.
• 🧪 Genetic Testing: Confirms TBX5 mutation, useful for family studies.
• 📈 ECG: May reveal conduction delays, sinus node disease, or AV block.

🛠️ Management

• Cardiac: Surgical repair of septal defects, pacemaker for conduction abnormalities.
• Skeletal: Orthopedic correction, splinting, or prosthetics for upper limb malformations.
• Genetic counseling: Essential for affected families due to autosomal dominant inheritance.
• Multidisciplinary care: Involving cardiology, orthopedics, genetics, and physiotherapy improves outcomes.
• Long-term: Regular cardiac follow-up for arrhythmia surveillance and progressive cardiac disease.

📚 Exam tip: If you see a child with absent radius on X-ray + atrial septal defect → think Holt-Oram syndrome. 💡 Compare with TAR (Thrombocytopenia-Absent Radius) syndrome, where thumbs are present, helping distinguish it from Holt-Oram.