RT Journal Article
SR Electronic
T1 Cardiac valve involvement in <em>ADAR</em>-related type I interferonopathy
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 475
OP 478
DO 10.1136/jmedgenet-2019-106457
VO 57
IS 7
A1 Crow, Yanick
A1 Keshavan, Nandaki
A1 Barbet, Jacques Patrick
A1 Bercu, Geanina
A1 Bondet, Vincent
A1 Boussard, Charlotte
A1 Dedieu, Nathalie
A1 Duffy, Darragh
A1 Hully, Marie
A1 Giardini, Alessandro
A1 Gitiaux, Cyril
A1 Rice, Gillian Inara
A1 Seabra, Luis
A1 Bader-Meunier, Brigitte
A1 Rahman, Shamima
YR 2020
UL http://jmg.bmj.com/content/57/7/475.abstract
AB Background Adenosine deaminases acting on RNA (ADAR) mutations cause a spectrum of neurological phenotypes ranging from severe encephalopathy (Aicardi-Goutières syndrome) to isolated spastic paraplegia and are associated with enhanced type I interferon signalling. In children, non-neurological involvement in the type I interferonopathies includes autoimmune and rheumatological phenomena, with calcifying cardiac valve disease only previously reported in the context of MDA5 gain-of-function.Results We describe three patients with biallelic ADAR mutations who developed calcifying cardiac valvular disease in late childhood (9.5–14 years). Echocardiography revealed progressive calcification of the valvular leaflets resulting in valvular stenosis and incompetence. Two patients became symptomatic with biventricular failure after 5–6.5 years. In one case, disease progressed to severe cardiac failure despite maximal medical management, with death occurring at 17 years. Another child received mechanical mitral and aortic valve replacement at 16 years with good postoperative outcome. Histological examination of the affected valves showed fibrosis and calcification.Conclusions Type I interferonopathies of differing genetic aetiology demonstrate an overlapping phenotypic spectrum which includes calcifying cardiac valvular disease. Individuals with ADAR-related type I interferonopathy may develop childhood-onset multivalvular stenosis and incompetence which can progress insidiously to symptomatic, and ultimately fatal, cardiac failure. Regular surveillance echocardiograms are recommended to detect valvular disease early.