ichthyosis: evidence from a worldwide online survey

27 X-linked ichthyosis (XLI) is a rare dermatological condition arising from deficiency for the enzyme 28 steroid sulfatase (STS). Preliminary evidence in boys with XLI, and animal model studies, suggests that 29 individuals lacking STS are at increased risk of developmental disorders and associated traits. 30 However, the behavioural profile of children with XLI is poorly-characterised, and the behavioural 31 profile of adults with XLI has not yet been documented at all. 32 Using an online survey, advertised worldwide, we collected detailed selfor parent-reported 33 information on behaviour in adult (n=58) and younger (≤18yrs, n=24) males with XLI for comparison 34 to data from their non-affected brothers, and age/gender-matched previously-published normative 35 data. The survey comprised demographic and background information (including any prior clinical 36 diagnoses) and validated questionnaires assaying phenotypes of particular interest (Adult ADHD Self37 Report Scale v1.1, Barrett Impulsiveness Scale-11, adult and adolescent Autism Quotient, Kessler 38 Psychological Distress Scales, and Disruptive Behaviour Disorder Rating Scale). Individuals with XLI 39 generally exhibited normal sensory function. Boys with XLI were at increased risk of developmental 40 disorder, whilst adults with the condition were at increased risk of both developmental and mood 41 disorders. Both adult and younger XLI groups scored significantly more highly than male general 42 population norms on measures of inattention, impulsivity, autism-related traits, psychological distress 43 and disruptive behavioural traits. 44 These findings indicate that both adult and younger males with XLI exhibit personality profiles 45 that are distinct from those of males within the general population, and suggest that individuals with 46 XLI may be at heightened risk of psychopathology. The data are consistent with the notion that STS is 47 important in neurodevelopment and ongoing brain function, and with previous work suggesting high 48 rates of developmental disorders in boys with XLI. Our results suggest that individuals with XLI may 49 require medical care from multidisciplinary teams, and should help to inform genetic counselling for 50 the condition. 51