| Condition | Radius | Thumb | Cardiac Defects | Other Key Features | Gene |
|---|---|---|---|---|---|
| Holt-Oram syndrome | Absent/hypoplastic, usually variable and often asymmetric | Absent/hypoplastic/triphalangeal | Very common: ASD, VSD, conduction defects | Upper limb defect mainly; lower limbs usually normal | TBX5 |
| Thrombocytopenia-absent radius (TAR) | Bilateral absent radius | Thumbs present, often abnormal | Usually not characteristic | Thrombocytopenia, bilateral symmetric defect | RBM8A |
| Fanconi anemia | Radial ray hypoplasia/absence | Thumb abnormalities | Variable | Renal, vertebral, pigmentary abnormalities; growth restriction | Multiple, incl. FANCA |
| VACTERL | May have radial-ray defect | Variable | VSD/other CHD | Vertebral + anorectal + cardiac + tracheoesophageal + renal + limb anomalies | Heterogeneous |
| Townes-Brocks | Radius/thumb abnormalities may occur | Triphalangeal/bifid/absent thumb | CHD possible | Anal + ear anomalies, renal abnormalities | SALL1 |
| Diamond-Blackfan anemia | Usually thumb abnormality; radius can be affected | Triphalangeal/bifid/absent | Possible | Postnatal anemia, short stature | Ribosomal protein genes |
| Duane-radial ray syndrome | Radial ray abnormalities | Thumb abnormalities | Variable | Duane anomaly, facial/renal abnormalities | SALL4 |
| Baller-Gerold syndrome | Radial ray abnormalities | Variable | Not typical | Craniosynostosis | RECQL4 |
1. Holt-Oram syndrome
• TBX5-related
• Upper limb: radius hypoplasia/aplasia, abnormal carpus, absent/hypoplastic or triphalangeal thumb
• Cardiac defects occur in roughly three-quarters of affected individuals, but some have no structural cardiac defect
• Conduction abnormalities may occur later
• Can be unilateral/asymmetric
2. Fanconi anemia / Fanconi radial-ray phenotype
• Radius and thumb abnormalities can be very similar
• Look carefully for bilateral renal anomalies, vertebral abnormalities, growth abnormalities and other skeletal findings
• Prenatally, absence of additional anomalies does not completely exclude it.
3. SALL4-related disorder
• Particularly consider Duane-radial ray syndrome
• Examine the eyes/orbits, ears, kidneys and other skeletal structures.
• SALL4 disorders can closely mimic Holt-Oram.
4. TAR syndrome
• Much less likely if the thumb is truly absent.
• TAR classically has bilateral absent radii with thumbs preserved.
• 17 weeks
• Unilateral absent radius
• Unilateral absent thumb
• Humerus normal
• Contralateral upper limb normal
• Radial deviation of the affected hand
• No cardiac abnormality identifie
this is a true unilateral radial-ray defect with thumb aplasia.
1. Holt-Oram syndrome, TBX5-related
Holt-Oram can be unilateral and markedly asymmetric. The combination of radial deficiency + absent thumb is compatible. The normal heart does not exclude TBX5-related disease, particularly at 17 weeks.
2. SALL4-related disorder / Duane-radial ray syndrome
This deserves particular attention because SALL4-related radial-ray abnormalities can be unilateral/asymmetric and may include:
• absent/hypoplastic radius
• absent/hypoplastic thumb
• radial deviation of the hand
External ear abnormalities, renal anomalies and other skeletal abnormalities.
3. Fanconi anemia
Consider particularly if there are additional skeletal, renal or vertebral abnormalities, although an isolated prenatal unilateral defect is less characteristic.
4. TAR syndrome is unlikely
The absent thumb argues strongly against TAR, because TAR characteristically has bilateral absent radii with preserved thumbs.