The Western Australian Family Connections Genealogical Project: Detection of familial occurrences of single gene and chromosomal disorders

Aim: To investigate using a Western Australian (WA) genealogical database for the identification of single gene and chromosome disorders among families. Method: Hospital admissions for single gene and chromosome disorders recorded during 2000–2006 were identified from the WA Hospital Morbidity Data System. The proportion of these conditions occurring in family groups was then identified using genealogical links created through the WA Family Connections Genealogical Project. Results: There were 216 family clusters among 11,303 people who were recorded as having a genetic or chromosomal disorder on their hospital admission record. The most common single gene conditions found to occur in multiple family members included blood clotting disorders such as Factor VIII deficiency and Von Willebrand’s disease, followed by cystic fibrosis, myotonic dystrophies, neurofibromatosis, tuberous sclerosis, and osteogenesis imperfecta. Discussion: Single gene disorders most commonly occurring in multiple family members have been identified using the WA Family Connections Genealogical Project. These disorders reflect the most common single gene disorders requiring hospital admission, but which are not fatal before reproductive age and do not result in a loss of fertility. They are also restricted to disorders with earlier onset, as the WA Family Connections Genealogical Project currently covers 2–3 of the most recent generations. This study demonstrates the utility of record linkage genealogies to identify kindred with genetic disorders, offering a rich resource of information for focused genetic epidemiological research

Deconstructing the repetitive behaviour phenotype in Autism Spectrum Disorder 1 through a large population-based analysis

Objective Restricted and repetitive pattern of behaviours and interests (RRB) are a cardinal feature of autism spectrum disorder (ASD), but there remains uncertainty about how these diverse behaviours vary according to individual characteristics. This study provided the largest exploration to date of the relationship between Repetitive Motor Behaviours, Rigidity/Insistence on Sameness and Circumscribed Interests with other individual characteristics in newly diagnosed individuals with ASD. Method Participants (N = 3,647; 17.7% females; Mage = 6.6 years [SD = 4.7]) were part of the Western Australian (WA) Register for ASD, an independent, prospective collection of demographic and diagnostic data of newly diagnosed cases of ASD in WA. Diagnosticians rated each of the DSM‐IV‐TR criteria on a 4‐point Likert severity scale, and here we focused on the Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests symptoms. Results The associations between RRB domains, indexed by Kendall's Tau, were weak, ranging from non‐significant for both Circumscribed Interests and Repetitive Motor Behaviours to significant (.20) for Insistence on Sameness and Repetitive Motor Behaviours. Older age at diagnosis was significantly associated with lower Circumscribed Interests and significantly associated with higher Insistence on Sameness and Repetitive Motor Behaviours. Male sex was significantly associated with higher Repetitive Motor Behaviours but not Insistence on Sameness or Circumscribed Interests. Conclusions The pattern of associations identified in this study provides suggestive evidence for the distinctiveness of Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests, highlighting the potential utility of RRB domains for stratifying the larger ASD population into smaller, more phenotypically homogeneous subgroups that can help to facilitate efforts to understand diverse ASD aetiology and inform design of future interventions

Autism and Intellectual Disability Are Differentially Related to Sociodemographic Background at Birth

Background: Research findings investigating the sociodemographics of autism spectrum disorder (ASD) have been inconsistent and rarely considered the presence of intellectual disability (ID). Methods: We used population data on Western Australian singletons born from 1984 to 1999 (n = 398,353) to examine the sociodemographic characteristics of children diagnosed with ASD with or without ID, or ID without ASD compared with non-affected children. Results: The profiles for the four categories examined, mild-moderate ID, severe ID, ASD without ID and ASD with ID varied considerably and we often identified a gradient effect where the risk factors for mild-moderate ID and ASD without ID were at opposite extremes while those for ASD with ID were intermediary. This was demonstrated clearly with increased odds of ASD without ID amongst older mothers aged 35 years and over (odds ratio (OR) = 1.69 [CI: 1.18, 2.43]), first born infants (OR = 2.78; [CI: 1.67, 4.54]), male infants (OR = 6.57 [CI: 4.87, 8.87]) and increasing socioeconomic advantage. In contrast, mild-moderate ID was associated with younger mothers aged less than 20 years (OR = 1.88 [CI: 1.57, 2.25]), paternal age greater than 40 years (OR = 1.59 [CI: 1.36, 1.86]), Australian-born and Aboriginal mothers (OR = 1.60 [CI: 1.41, 1.82]), increasing birth order and increasing social disadvantage (OR = 2.56 [CI: 2.27, 2.97]). Mothers of infants residing in regional or remote areas had consistently lower risk of ASD or ID and may be linked to reduced access to services or underascertainment rather than a protective effect of location. Conclusions: The different risk profiles observed between groups may be related to aetiological differences or ascertainment factors or both. Untangling these pathways is challenging but an urgent public health priority in view of the supposed autism epidemic

Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study

Objective:Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrumdisorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex.Method:This is a population-based cohort study of livebirths from 1998 to 2007 in California, Denmark, Finland, Israel, Sweden and WesternAustralia followed through 2011 to 2015. Subjects were monitored for an ASD diagnosis in their older siblings or cousins (exposure) and for their ASDdiagnosis (outcome). The relative recurrence risk was estimated for different sibling and cousin pairs, for each site separately and combined, and by sex.Results:During follow-up, 29,998 cases of ASD were observed among the 2,551,918 births used to estimate recurrence in ASD and 33,769 cases ofchildhood autism (CA) were observed among the 6,110,942 births used to estimate CA recurrence. Compared with the risk in unaffected families, therewas an 8.4-fold increase in the risk of ASD following an older sibling with ASD and a 17.4-fold increase in the risk of CA following an older sibling withCA. A 2-fold increase in the risk for cousin recurrence was observed for the 2 disorders. There also was a significant difference in sibling ASD recurrencerisk by sex.Conclusion:The present estimates of relative recurrence risks for ASD and CA will assist clinicians and families in understanding autism risk in thecontext of other families in their population. The observed variation by sex underlines the need to deepen the understanding of factors influencing ASD familial risk.</p

Sertraline for anxiety in adults with a diagnosis of autism (STRATA) : study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial

Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. Methods: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration: ISRCTN, ISRCTN15984604. Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021

Linked data: Opportunities and challenges in disability research

'Background': Disability research data often exist in the form of individual records located within discrete registers that may extend across sensitive political boundaries. 'Method': This paper discusses the opportunities and challenges associated with using linked health and administrative data for disability research, with examples from research projects conducted both in Australia and overseas. 'Results': Linked data offer distinct value in providing a comprehensive profile for a range of health issues, such as morbidity, mortality, assessing health care costs and/or quality of service provision. 'Conclusions': While the use of record linkage in health research is not a novel concept, recent advances in technology and electronic data management plus improved data linkage protocols have markedly increased the feasibility and opportunity for successfully utilising data linkage for the purposes of research, while at the same time protecting the privacy of the individual. An awareness and appropriate management of the associated challenges is required to maximise the outcomes of disability research using linked data

The four ages of Down syndrome

Down syndrome (DS) affects 1 per 650-1000 live births and is the most common known genetic cause of intellectual disability. A highly significant change in the survival of people with DS has occurred during the last two generations, with life expectancy estimates increasing from 12 to nearly 60 years of age. Subjects and Methods: Detailed information on 1332 people in Western Australia with DS was abstracted from a specialist statewide database for the period 1953-2000 and electronically linked with three other state or national health and mortality data sources and the state Birth Defects Registry. Results: Over the last 25 years the percentage of women over 35 years giving birth increased from 4.8 to 18.6%, accompanied by an increase in the overall prevalence of DS from 1.1 to 2.9 per 1000 births. Four life stages of DS were identified: prenatal, childhood and early adulthood, adulthood, and senescence. Although pneumonia, or other types of respiratory infections, was the most common cause of death across the entire lifespan, ranging from 23% of deaths in adulthood to 40% in senescence, each life stage exhibited a particular profile of comorbidities. Congenital heart defects were common causes in childhood (13%) and adulthood (23%), whereas in senescence coronary artery disease (10%) and cardiac, renal, and respiratory failure (9%) were leading causes of mortality. Conclusions: A major re-appraisal in attitudes towards DS is required to ensure that the medical and social needs of people with the disorder are adequately met across their entire lifespan. In particular, specific recognition of the comorbidities that can arise at different ages is needed, accompanied by the provision of appropriate levels of care and management

The four ages of Down syndrome

Background: Down syndrome (DS) affects 1 per 650–1000 live births and is the most common known genetic cause of intellectual disability. A highly significant change in the survival of people with DS has occurred during the last two generations, with life expectancy estimates increasing from 12 to nearly 60 years of age. Subjects and Methods: Detailed information on 1332 people in Western Australia with DS was abstracted from a specialist statewide database for the period 1953–2000 and electronically linked with three other state or national health and mortality data sources and the state Birth Defects Registry. Results: Over the last 25 years the percentage of women over 35 years giving birth increased from 4.8 to 18.6%, accompanied by an increase in the overall prevalence of DS from 1.1 to 2.9 per 1000 births. Four life stages of DS were identified: prenatal, childhood and early adulthood, adulthood, and senescence. Although pneumonia, or other types of respiratory infections, was the most common cause of death across the entire lifespan, ranging from 23% of deaths in adulthood to 40% in senescence, each life stage exhibited a particular profile of comorbidities. Congenital heart defects were common causes in child- hood (13%) and adulthood (23%), whereas in senescence coronary artery disease (10%) and cardiac, renal, and respiratory failure (9%) were leading causes of mortality. Conclusions: A major re-appraisal in attitudes towards DS is required to ensure that the medical and social needs of people with the disorder are adequately met across their entire lifespan. In particular, specific recognition of the comorbidities that can arise at different ages is needed, accompanied by the provision of appropriate levels of care and management

Psychosocial interventions and support groups for siblings of individuals with neurodevelopmental conditions: A mixed methods systemic review of sibling self-reported mental health and wellbeing outcomes

Siblings of persons with neurodevelopmental conditions (NDCs) have increased risk of poorer psychosocial functioning. This systematic review evaluated quantitative and qualitative evidence on sibling mental health and wellbeing outcomes following psychosocial interventions and the risk and protective factors associated with post-intervention outcomes. From 2025 identified studies published from 1991 to 2022 across ten databases, 24 studies were included. The largest immediate post-intervention improvements were in self-esteem, social wellbeing and knowledge of NDCs. The most sustained improvements in intervention groups at follow-up periods were in emotional and behavioural adjustment and NDC knowledge. There were positive, but small, differences in favour of the intervention groups on knowledge of NDCs, self-esteem, coping and the sibling relationship as compared to waitlist control groups. Psychosocial interventions for siblings are heterogeneous, and more data, including consideration of unique family circumstances, are needed to improve reporting and replicability, to measure effectiveness and tailor necessary supports