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).

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

Management

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.

References