A Late Diagnosis of Andersen-Tawil Syndrome in Teenage Siblings

Background

Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder characterized by a classic symptom triad, including periodic paralysis, ventricular arrhythmias with associated prolonged QT interval and U waves, and dysmorphic facial and skeletal features. Pathogenic variants of the KCNJ2 gene are linked to ATS.

Methods

We present two siblings with the same pathogenic mutation and facial characteristic of hypotelorism, yet with intrafamilial and sex-specific variability.

Results

The first patient is a 16-year-old male who presented from an outside hospital with subacute-onset weakness. The symptoms almost completely subsided the following day, with only mild proximal muscle weakness. Magnetic resonance imaging of the brain and cervical spine was unremarkable. He had one prior attack of self-resolving weakness without apparent triggering factors and a history of premature ventricular contractions and U waves seen on electrocardiogram without cardiac symptoms. On further evaluation his physical examination was significant for micrognathia, hypotelorism, and clinodactyly. Electrodiagnostic examination showed no clear evidence of polyneuropathy. Given his presentation of the typical triad of periodic weakness, dysmorphic features, and cardiac rhythm abnormalities, genetic testing was pursued revealing a pathogenic mutation of the KCNJ2 gene, indicative of ATS. Subsequent genetic testing of his older biological sister, with identical physical features but without a history of cardiac symptoms or episodic periodic paralysis, revealed the same pathogenic mutation.

Conclusions

It is essential to note that ATS can manifest with a wide range of symptoms and some individuals may display only subtle or atypical signs, contributing to this challenging diagnosis.