Molecular Genetics of S tüve– W iedemann Syndrome

Abstract

Stüve–Wiedemann syndrome (STWS; OMIM #610559) is a rare bent‐bone dysplasia that includes radiologic bone anomalies, respiratory distress, feeding difficulties and hyperthermic episodes. STWS usually results in infant mortality, yet some STWS patients survive at least into early adolescence. STWS is caused by a mutation in the leukaemia inhibitory factor receptor ( LIFR ) gene, which is inherited in an autosomally recessive pattern. Most LIFR mutations resulting in STWS are null mutations which cause instability of the mRNA (messenger ribonucleic acid), preventing the formation of LIFR and impairing the signalling pathway. LIFR signalling usually follows the JAK/STAT3 pathway, and is initiated by several interleukin‐6‐type cytokines. STWS is managed on a symptomatic basis, because there is no treatment currently available. Key Concepts STWS comprises multiple symptoms affecting multiple physiological systems. Mutations in LIFR cause mRNA instability, preventing the formation of LIFR protein. LIFR is important for many IL‐6 cytokine family members; and in the case of LIFR mutations, activities of several cytokines are impaired. The JAK/STAT3 pathway plays a critical role in STWS.