Procedures

We obtained diagnostic genomic reports, including genetic inheritance information (de novo or inherited) if available, from participants' UK National Health Service (NHS) medical records or directly from their families (appendix p 2). For individuals with multiple genetic variants, subsequent data analysis was based on the most pathogenic variant.

Primary caregivers were invited to complete all questionnaires regarding their child, including online assessments of their child's educational progress and physical and mental health using the Development and Well-Being Assessment (DAWBA), which is organised into modules and includes a combination of open text, binary questions, and Likert scale questions, and the Strengths and Difficulties Questionnaire (SDQ; appendix p 3).^{12, 13}Daily living skills were measured using the Adaptive Behaviour Assessment System 3 (ABAS-3).¹⁴ A developmental quotient was calculated from primary caregivers' estimates of the child's mental age divided by their chronological age.^{7, 15} A structured supplemental medical history questionnaire gathered information about the child's time in utero, birth, early development, current medical problems, medication, and included information on special educational needs, educational health care plans¹⁶ and disability living allowance.¹⁷ Postcodes of participating family homes were ranked on an index of multiple deprivation (IMD), provided by the UK Office for National Statistics.^{18, 19} In the current English Indices of Deprivation 2019, seven domains of deprivation are considered and weighted as follows: income (22·5%), employment (22·5%), education (13·5%), health (13·5%), crime (9·3%), barriers to housing and services (9·3%), and living environment (9·3%). The indices of multiple deprivation for Wales, Scotland, England, and Northern Ireland are calculated separately.

The Mental Health of Children and Young People in England 2017 Survey is funded by the Department of Health and Social Care, commissioned by NHS Digital, and carried out by the National Centre for Social Research, the Office for National Statistics, and Youthinmind, to provide data on trends in child mental health in England. DSM-5 disorder prevalence rates from the 2017 national survey were used as a comparator group in this study.⁹