1. Roberts syndrome / SC phocomelia
ESCO2, autosomal recessive
Most important genetic cause of true phocomelia
Symmetric or asymmetric severe limb reduction
May have oligodactyly, flexion contractures, craniofacial anomalies, cleft lip/palate, micrognathia, microcephaly and severe FGR
Cardiac, renal and CNS anomalies may coexist
2. Thalidomide embryopathy
Classic acquired cause
Exposure during 4–8 weeks is particularly relevant
Characteristic severe reduction/absence of proximal limb segments
Can involve upper limbs more severely than lower limbs
Ear, cardiac and ocular abnormalities may coexist
3. Chromosomal abnormalities
Especially trisomy 18
Other chromosomal imbalance/rearrangements can produce limb-reduction phenotypes
4. Thrombocytopenia-absent radius (TAR)
Bilateral absent radii with thumbs preserved
Not technically classic phocomelia, but an important differential for severe upper-limb reduction
5. Fanconi anemia / radial-ray syndromes
Radial aplasia/hypoplasia, thumb abnormalities and other skeletal defects
Usually less dramatic than classic phocomelia
6. Vascular disruption / amniotic bands
Usually asymmetric
Irregular amputations or constriction rings
Associated with an otherwise relatively normal skeleton
7. Maternal diabetes and other teratogenic exposures
Maternal pregestational diabetes can increase the risk of caudal and limb anomalies
Other rare teratogens may produce limb-reduction phenotypes
