RIDDLE Syndrome (RNF168)
RIDDLE is an acronym for radiosensitivity, immunodeficiency dysmorphic features, and learning difficulties syndrome, due to mutations in the RNF168 gene. Other clinical signs of RIDDLE syndrome may include mild ataxia, microcephaly, normal intelligence, conjunctival telangiectasia, recurrent sinus infections, decreased serum IgG and IgA, increased alpha-fetoprotein (AFP), and late onset of pulmonary fibrosis.
Stewart et al. (2007) first described RIDDLE syndrome in a patient with increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Mutations in the RNF168 gene cause an autosomal recessive form of combined immunodeficiency with syndromic features and associated with immunoglobulin deficiency and cellular radiosensitivity (Stewart et al. 2009; Devgan et al. 2011; Chinn et al. 2017; Picard et al. 2018; Pietrucha et al. 2017). The RNF168gene is...