Phocomelia and Thalidomide
🧪 Thalidomide Embryopathy is a congenital malformation syndrome caused by thalidomide exposure in early pregnancy.
The critical period for limb development is days 35–50 after last menstrual period.
Exposure outside this window usually does not cause limb defects.
Pathogenesis involves interference with angiogenesis and growth signalling in the developing limb bud.
📖 Aetiology
- Thalidomide exposure: Classically associated with phocomelia, but not all cases of phocomelia are thalidomide-induced.
- Safe if taken before day 34 or after day 50 post-LMP.
- Other risk factors: genetic syndromes with similar phenotype (see differentials).
🩺 Clinical Features
- Limb malformations:
- Phocomelia (most severe reduction defect).
- Radial/humeral hypoplasia, absent thumbs, three-jointed thumbs.
- Femoral and tibial hypoplasia.
- Ear and cranial anomalies: Absent auricles → deafness, facial and ocular muscle defects.
- Other organ involvement: Cardiac malformations, GI anomalies (atresias), uterine and gallbladder defects.
🔎 Investigations
- Genetic testing: To distinguish from inherited syndromes.
- Echocardiogram: To detect associated congenital heart disease.
- Additional imaging tailored to suspected anomalies (renal, GI, skeletal).
🧩 Differentials (Exam Pearls)
- Roberts-SC Phocomelia: AR, limb reduction + cleft palate + ear malformations.
- Holt-Oram (Heart-Hand Syndrome): AD, radial ray anomalies + cardiac septal defects.
- TAR Syndrome: Absent radii + thrombocytopenia (normal thumbs differentiate from thalidomide).
- Poland Sequence: Unilateral hand defect + absent pectoralis major muscle.
- Amniotic Band Syndrome: Asymmetrical "amputation-like" limb defects.
- Fanconi Anaemia: Radial aplasia + marrow failure (haematological features distinguish).
- Other mimics: Cornelia de Lange, LADD, Goldenhar, Moebius, VATER association.
⚕️ Management
- Multidisciplinary care: Genetics, orthopaedics, cardiology, ENT, physiotherapy.
- Surgery: Limb reconstruction, prosthetics, correction of organ malformations.
- Rehabilitation: Physical & occupational therapy to optimise independence.
- Monitoring: Lifelong support for cardiac, hearing, and developmental complications.
🌟 Key Clinical Pearl: Thalidomide exposure taught the medical world the importance of teratogenicity testing and strict drug regulation.
Today, thalidomide is still used (e.g. multiple myeloma, leprosy) but only under strict pregnancy prevention programmes.
📚 Reference
