Cardiac phenotype in children with X-linked ichthyosis (STS-sEDD): findings from a prospective cohort

X-linked ichthyosis is caused by pathogenic variants or deletions involving STS 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 (STS-sEDD). 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 5-day ambulatory electrocardiographic monitoring. Genetic findings were reviewed, and 11 obligate-carrier mothers also underwent cardiological assessment. 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; 5-day monitoring in 13 detected no clinically significant arrhythmia. Twelve patients had contiguous-gene deletions and two had pathogenic STS 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.

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.

• X-linked ichthyosis is caused by STS variants or deletions that may involve contiguous genes. • Cardiac arrhythmias have been reported with Xp22.31 deletions, but pediatric data are scarce.

• No clinically significant arrhythmia was found in 14 boys undergoing multimodal assessment. • Deletion extent did not predict cardiac findings; follow-up should reflect symptoms and family history.