Multisystemic Assessment in Andersen-Tawil Syndrome: Report of Eighteen Individuals

Background/Objectives: Andersen-Tawil Syndrome (ATS) is an ultra-rare autosomal dominant condition secondary to deleterious variants in KCNJ2 or KCNJ5 in the majority of patients. It is variably characterized by a triad of Long QT Syndrome (LQTS)/ventricular arrhythmias with a prominent U-wave, episodic flaccid muscle weakness/paralysis and skeletal abnormalities. Other clinical features include distinctive facial dysmorphisms, dental anomalies, and mild learning difficulties. Limited data are available regarding the initial presenting sign or symptoms of ATS. Methods: In this study, we include data from 18 patients across eight families. In our cohort, the main clues that led probands to genetic testing were syncope (three families), which was associated with dysmorphic features in one case; LQTS (one family); asymptomatic premature ventricular contractions (PVCs) (three families); and a case incidentally identified during routine cardiac evaluations and due to short stature (one family). Results: Following thorough investigations, a prolonged QT interval was detected in five individuals and prominent U-waves were observed in the majority of the court. Distinctive facial features were consistently present (100%) and can be suggested as a clinical tool for accelerated diagnosis. Skeletal manifestations ranged from 37.5% to 93.7% including short stature, scoliosis and finger defects. Only two patients showed periodic paralysis (PP). Conclusions: Regarding the clinical management of ATS, we underline the importance of the multidisciplinary, personalized, and longitudinal approach, where arrhythmia may not be the leading sign but remains the most potentially critical prognostic factor.