Ventricular arrhythmia and Noonan Syndrome with LZTR1 Mutations: Expanding the Phenotype with a Case Report and Review of the Literature

Background Noonan syndrome (NS) is characterized by typical facial features, short stature, congenital heart defects and other comorbidities, which is caused by germline mutations in genes coding for components of the Ras-mitogen-activated protein kinase (RAS-MAPK) pathway. Noonan syndrome is an inherited disease involving multiple systems, but ventricular arrhythmia in Noonan syndrome is rarely reported. Methods Here we report a 15-years old patient with LZTR1-associated Noonan syndrome, who has congenital heart defect, ventricular arrhythmia, bundle branch block, pectus excavatum, costal eversion, scoliosis, myopia, growth retardation and hearing loss. Genetic testing revealed that the patient had a novel heterozygous variant c.313delT (p.trp105Glyfs*42) mutation in the LZTR1. Results We provide a review of the literature of LZTR1 mutations and find that approximately 6% of published cases have ventricular arrhythmia. Conclusions Our findings expand on the Noonan syndrome phenotype and suggest that mutations in the LZTR1 gene are involved in ventricular arrhythmia.