Holt Oram syndrome

Holt-Oram syndrome (HOS) is an autosomal dominant syndrome that results in congenital heart defects and upper limb anomalies:

• congenital heart defects 
  • atrial septal defect (ASD) (commonest cardiac defect )
  • ventricular septal defect (VSD)
• aortic coarctation
• upper limb abnormalities
  • radial ray anomalies, e.g. radial aplasia, radial hypoplasia, radial fusion
  • thumb anomalies, e.g thumb aplasia
• phocomelia
• clavicle hypoplasia

Pathology

Genetics 

A large proportion of affected individuals have mutations in the TBX5 gene. It is thought to carry an autosomal dominant inheritance with full penetration but variable expression. However between 50 and 80% of cases may be due to new mutations.

Radiographic features

Antenatal ultrasound

The diagnosis can be suspected amongst the differential if upper limb abnormalities are noted along with heart defects on fetal ultrasound. The limb defects can be asymmetrical.

History and etymology

Two British cardiologists, Mary Clayton Holt (1924-1993) and Samuel Oram (1913-1991) , described the condition in 1960 .

Differential diagnosis

General considerations include

• Aase syndrome
• VACTERL association
• TAR syndrome: thrombocytopenia - absent radius syndrome

Siehe auch:

• VACTERL-Assoziation
• Radiusaplasie
• Aase-Smith-Syndrom
• Thrombozytopenie-Radiusaplasie-Syndrom
• Dreigliedriger Daumen-Polysyndaktylie-Syndrom
• Radialstrahldefekte
• Okihiro-Syndrom

und weiter:

• Karpale Koalition
• Atriumseptumdefekt
• Os carpale
• dreigliedriger Daumen
• Daumenaplasie
• Ventrikelseptumdefekt