Individuals with Miller syndrome have similar phenotypic characteristics to those with Nager syndrome, another rare monogenic disorder that primarily affects the craniofacial skeleton. In contrast to Miller syndrome, the limb defects observed in individuals with Nager syndrome affect the anterior elements of the upper limb. Nevertheless, it has been hypothesized that Miller and Nager syndromes were caused by different mutations in the same gene. We resequenced DHODH in twelve unrelated individuals diagnosed with Nager syndrome but found no pathogenic mutations (data not shown). Accordingly, Nager syndrome and Miller syndrome are either not allelic or Nager syndrome is caused exclusively by mutations in regulatory elements that alter the expression of DHODH.
