riddle syndrome riddle syndrome riddle syndrome is a rare genetic syndrome. the name is an acronym for radiosensitivity, immunodeficiency dysmorphic features and learning difficulties. riddle syndromeother namesradiosensitivity-immunodeficiency-dysmorphic features-learning difficulties syndromeriddle syndrome is inherited in an autosomal recessive pattern. presentation the features of this condition include: facial dysmorphism short stature mild motor control and learning difficulties mild ataxia microcephaly normal intelligence conjunctival telangiectasia recurrent sinus infections decreased serum iga late onset of pulmonary fibrosis increased alpha-fetoprotein increased radiosensitivity genetics this condition is due to mutations in the rnf168 gene. it is inherited in an autosomal recessive fashion. the gene encodes a ubiquitin ligase and is located on the long arm of chromosome 3 (3q29) on the crick (minus strand). diagnosis differential diagnosis the ddx is ataxia telangectasia artemis deficiency immunodeficiency 26 (pkcs gene deficiency) lig4 syndrome nijmegen breakage syndrome severe combined immunodeficiency with cernunnos x-linked agammaglobulinemia epidemiology this condition is rare. only four cases have been described up to 2017. history this syndrome was first described by stewart et al. 2007.