Abstract
<title>Abstract</title> <p> Purpose X-linked ichthyosis is caused by pathogenic variants or deletions involving <italic>STS</italic> at Xp22.31. Because some deletions include contiguous genes and cardiac rhythm abnormalities have been reported, we characterized the cardiac phenotype of children with genetically confirmed steroid sulfatase-related syndromic epidermal differentiation disorder ( <italic>STS</italic> -sEDD). Methods This prospective, observational, single-centre study included 14 boys aged 2–16 years. Assessment comprised clinical history and examination, 12-lead electrocardiography, echocardiography, exercise testing when age appropriate, and five-day ambulatory electrocardiographic monitoring. Genetic findings were reviewed, and 11 obligate-carrier mothers also underwent cardiological assessment. Results Nine patients (64%) were asymptomatic and five (36%) reported mild, nonspecific symptoms. Minor electrocardiographic findings in 11 patients were considered age-appropriate variants. All hearts were structurally normal except for one previously known, haemodynamically compensated partial anomalous pulmonary venous return. Exercise testing in 12 patients identified one isolated premature ventricular contraction; five-day monitoring in 13 detected no clinically significant arrhythmia. Twelve patients had contiguous-gene deletions and two had pathogenic <italic>STS</italic> sequence variants, with no apparent association between deletion extent and cardiac findings. Maternal echocardiograms were normal; one mother had isolated atrial and ventricular ectopy during exercise without clinically significant arrhythmia. Conclusion Clinically relevant cardiac involvement appeared uncommon in this small pediatric cohort. The sample size and cross-sectional assessment preclude definitive risk estimates; cardiological evaluation should be individualized according to symptoms, cardiovascular findings, and family history. </p>