RIDDLE syndrome

RIDDLE syndrome is a rare genetic syndrome. The name is an acronym for Radiosensitivity, ImmunoDeficiency Dysmorphic features and Learning difficulties.

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).

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 extremely rare. Only four cases have been described up to 2017.

History
This syndrome was first described by Stewart et al. 2007.