Acromesomelic dysplasia, Hunter-Thompson type (AMDH), Chondrodysplasia, Grebe type (AMDG) and Fibular hypoplasia and complex brachydactyly

Acromesomelic dysplasia, Hunter-Thompson type (AMDH; MIM 201250) and Chondrodysplasia, Grebe type (AMDG, MIM 200700) are autosomal recessive disorders caused by mutations in the growth/differentiation factor 5 (GDF5) gene.  AMDH and AMDG are characterized by severe prenatal onset growth retardation restricted to the limbs. The middle and distal segments of the limbs are more severely affected than the proximal parts. In AMDH, the lower limbs are more profoundly affected than the upper limbs and large joint dislocations are common.  In AMDG, hypomelia is more severe, but the upper and lower limbs are equally affected.  Reduction or absence of the proximal and middle phalanges of the fingers and toes is seen in both disorders; however, this anomaly is more prominent in AMDG with all fingers and toes ball-shaped and functionless. The axial skeleton is not affected and intelligence is normal in these disorders.

Fibular hypoplasia and complex brachydactyly (Du Pan syndrome; MIM 228900) is another autosomal recessive disorder caused by mutations in GDF5. The main findings in this disorder are severe reduction or absence of the fibula and complex brachydactyly.

Multiple synostoses syndrome 2 (SYNS2; MIM 610017), symphalangism, proximal, 1B (SYM1B; MIM 615298), brachydactyly, type A1, C (BDA1C; MIM 615072), brachydactyly, type A2 (BDA2; MIM 112600) and brachydactyly, type C (BDC; MIM 113100) are also caused by mutations in GDF5.