Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through whole-exome sequencing combined with high resolution array-CGH from DNA of a fetus presenting with early onset AMC, we identified biallelic loss-of-function mutations in _DST_ with a stop gain variant (NM_001144769.5:c.12208G>T: p.Glu4070*) on one allele and a 149 kb microdeletion including exons 26 to 83 of the _DST_ gene (arr[GRCh37] 6p12.1(56323554_56472573)x1) on the other allele. Transmission electron microscopy of the sciatic nerve revealed abnormal morphology of the peripheral nerve with severe hypomyelination associated with dramatic reduction of fiber density which highlight the critical role of _DST_ in peripheral nerve axonogenesis during development in human. Mutations in _DST_ cause hereditary sensory and autonomic neuropathies (HSAN) type VI which has been reported in several unrelated families with highly variable age of onset from fetal to adult onset. Our data enlarge the clinical spectrum and disease mechanisms of neurogenic AMC.