Podcast: We missed one for the 2024 year end summary: Proof of the importance of genetic testing in autism

It happens every year – this one belonged in the 2024 year end highlights but was published late in the year. Researchers at UCSD, UCLA and CHLA followed families with autism whose genetic test revealed a rare variant. Did it make a difference in care? Understanding? Referrals? Listen to this week’s podcast episode to learn all about it. If you are in need of a genetic test, here are some things to know: https://www.alliancegenda.org/genetic-testing

Reference here: https://www.sciencedirect.com/science/article/pii/S1098360024002673

While it may not seem like it, the COVID-19 pandemic brought some advances in care and understanding for people on the spectrum. One example is the development and validity of remotely administered assessments that families can participate in from home rather than travel to a clinic. These tools were built out of necessity, and are evolving into a set of tools that can be used to build better outcome measures for clinical trials. This round focused on those with autism and a rare genetic variant or “neurogenetic syndromes” since these individuals have a known biological etiology of autism. However, they may be further improved to be utilized across the autism spectrum. Listen to this week’s podcast episode to learn more.

https://pubmed.ncbi.nlm.nih.gov/39643599

https://pubmed.ncbi.nlm.nih.gov/39526825

In this week’s episode, special podcast correspondent #MiaKotikovski summarizes new research on the increasing prevalence of autism, with a focus on females. While the number of diagnosed females is increasing faster than the number for males, females assigned at birth still are less likely to receive a diagnosis than males. Additional evidence points to females having more genetic mutations and lower cognitive ability, so the questions remain: Are there females with autism who are just not getting diagnosed despite having all the autism features? Why not? Does autism in females “look” the same as autism in males? What sets them apart? These articles are all featured in the year-end highlight of research, so this is the time to get a deep explanation of the latest in sex differences in #autism.

https://pubmed.ncbi.nlm.nih.gov/34563942

https://pubmed.ncbi.nlm.nih.gov/39334436

https://pubmed.ncbi.nlm.nih.gov/33966484

Profound autism refers to a subset of individuals with autism spectrum disorder who have an intellectual disability with an intelligence quotient less than 50 and minimal-to-no language and require 24-hour supervision and assistance with activities of daily living. The general pediatrician will invariably work with autistic children across the spectrum and will likely encounter youth with profound autism. Awareness of profound autism as a real entity describing autistic children with concomitant intellectual disability and language impairment who require 24-hour care is the first step in developing a solid pediatric home for these youth.

Objectives: Autism spectrum disorder (ASD) is estimated to be ∼10 times higher in children with versus without an autistic sibling in population-based studies. Prospective studies of infant siblings have revealed even higher familial recurrence rates. In the current prospective longitudinal study, we provide updated estimates of familial ASD recurrence using a multinational database of infants with older autistic siblings.

Methods: Data were collated across 18 sites of the Baby Siblings Research Consortium, an international network studying the earliest manifestations of ASD. A total of 1605 infants with an older autistic sibling were followed from early in life to 3 years, when they were classified as ASD or non-ASD. Hierarchical generalized linear modeling, with site as a random effect, was used to examine predictors of recurrence in families and calculate likelihood ratios.

Results: A total of 20.2% of siblings developed ASD, which is not significantly higher than the previously reported rate of 18.7%. Male infant sex and >1 older affected sibling were significant predictors of familial recurrence. Proband sex also influenced recurrence rates, with siblings of female probands significantly more likely to develop ASD than siblings of male probands. Race and maternal education were also associated with recurrence in families.

Conclusions: The familial recurrence rate of ASD, as measured in infant sibling studies, has not changed appreciably since previous estimates were made in 2011. Younger siblings of autistic children, particularly those who are male, have an affected female sibling, multiple affected siblings, or are impacted by social inequities, should be closely monitored and promptly referred for diagnostic evaluation.

Autism spectrum disorder (ASD) is a heterogeneous condition that affects development and functioning from infancy through adulthood. Efforts to parse the heterogeneity of the autism spectrum through subgroups such as Asperger’s and Profound Autism have been controversial, and have consistently struggled with issues of reliability, validity, and interpretability. Nonetheless, methods for successfully identifying clinically meaningful subgroups within autism are needed to ensure that research, interventions, and services address the range of needs experienced by autistic individuals. The purpose of this study was to generate and test whether a simple set of questions, organized in a flowchart, could be used in clinical practice and research to differentiate meaningful subgroups based on individuals’ level of functioning. Once generated, subgroups could also be compared to the recently proposed administrative category of Profound Autism and to groupings based on standardized adaptive measures. Ninety-seven adults with autism or related neurodevelopmental disorders participating in a longstanding longitudinal study, or their caregivers if they could not answer for themselves, completed phone interviews when the participants were ~30 years old. Information from these phone interviews was used to generate vignettes summarizing characteristics and aspects of the daily lives of each participant (e.g., language level, vocational activities, and social relationships). Three expert clinicians then used these vignettes to classify each participant based on their level of support needs. Meaningfully distinct subgroups within the sample were identified which could be reliably distinguished from one another. Implications of such categorizations and future directions are discussed.

Purpose: Most assessment tools used to diagnose and characterize autism spectrum disorder (ASD) were developed for in-person administration. The coronavirus disease 2019 (COVID-19) pandemic resulted in the need to adapt traditional assessment tools for online administration with only minimal evidence to support validity of such practices.

Methods: The current exploratory study compared scores from online administration of the Kaufman Brief Intelligence Test, Second Edition (KBIT-2) during the pandemic to scores derived from follow-up testing using traditional in-person administration. Participants were 47 children and adolescents (M age = 9.48 years, SD = 4.06; 68.10% male) who participated in a telehealth diagnostic evaluation for ASD that included online administration of the KBIT-2. Participants were invited to complete the KBIT-2 a second time during an in-person study visit.

Results: Pearson’s correlation coefficients suggested acceptable to good reliability between online and in-person administration. Although most participants’ online and in-person scores were within one standard deviation of each other, results suggested statistically significant differences between scores derived from the two modalities. Additionally, 19-26% of participants (depending on domain examined) had scores that differed by more than one standard deviation. Notably, all but one of these participants was under the age of 12 years.

Conclusion: Findings suggest that online administration of the KBIT-2 is likely appropriate for older children and adolescents with ASD. However, additional research is needed to test online administration of intellectual assessments for children with ASD.

Are you the grandparent, cousin, aunt, uncle, sibling, or half-sibling of someone with autism and wondered “what is the likelihood of autism in families, and the likelihood of comorbid conditions if I have a family member with autism?” Listen to this week’s podcast. Researchers at the AJ Drexel Autism Research Institute and Aarhus University in Denmark collaborated to calculate probabilities between autism in a person and dozens of other comorbid conditions in family members. They not only made the paper open to the public for everyone to read it, but they also created a publicly available data visualization tool so anyone can go on and look at specific situations of particular family relationships relating to anything from autoimmune conditions to mental health and psychiatric diagnosis. Links below for reference:

https://pubmed.ncbi.nlm.nih.gov/39283002

Interactive graphs: https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots_16918786403110/e-Figure5

Ensuring children are safe during the night can be a major concern for autism families. Up to 80% of children with autism experience sleep disturbances, and caregivers express concern about elopement, self-injury, and other risks that may be incurred by a child who has difficulty sleeping through the night. Safeguarding against these risks can be challenging and lead to many sleepless nights for the parents as well as the child. This project will use data gathered through remote interviews and daily sleep diaries to adapt a newly formed questionnaire that can be validated and used as a quantitative measure of caregivers’ safety-related concerns. There will be a special focus on the concerns of underrepresented groups such as families of color, those from socioeconomically disadvantaged communities, and families supporting children with additional disabilities. Additionally, objectively measured sleep data from a larger existing study will be used to assess how caregiver safety concerns relate to the actual sleep patterns of both the child and caregiver. The ability to document and measure safety-related concerns in diverse communities and identify sleep patterns linked to these concerns will lead to better understanding and more effective targeting of the specific needs of families.

Many autistic people have worse daily living skills (DLS) than would be expected based on their intellectual ability (IQ). Better daily living skills have been linked to more positive outcomes in those with autism.  Previous research looking at the gap between DLS and IQ focused on individuals at a single point in time, providing a snapshot of their current abilities rather than assessing these abilities across the lifespan. This study will better describe the discrepancy in DLS and IQ by engaging an existing longitudinal cohort of autistic individuals that has been followed from 2-33 years of age, focusing on specific DLS rather than lumping them all together.  These findings will allow for more focused intervention targets in adults with profound autism.

Instead of grouping together people with autism based on traditional severity scores, what if groupings were done based on functional outcome? Would this help better understand the broad spectrum of autism and why some people with autism are so different than others? Researchers at the University of Minnesota led by Kyle Sterrett, together with UCLA and UNC utilized a study that followed children with autism in the early 1990’s into their adulthood, in the 2020’s. They created and asked these families a set of questions (included in the manuscript below) to help identify levels of functioning in people with autism. This was done to help them and their families get the right support at right time. They found that these questions could differentiate people with Profound Autism based on things like level of independence and safety concerns. Dr. Sterrett talks with us on this week’s podcast to explain what they did and why it is so important.

https://pubmed.ncbi.nlm.nih.gov/39031157

What is the probability of having a future child with autism if you already have one or more? Families want to know. It helps preparation, planning, will hopefully improve early screening and supports. The Baby Siblings Research Consortium analyzed a bigger group of siblings compared to their 2011 numbers and found the recurrence pretty stable – 1 in 5 siblings will have an autism diagnosis compared to 1 in 36 in the general population. However, this number depends on a lot of things: Sex of infant, sex of sibling with an existing ASD diagnosis, number of autistic children in the family, race and socioeconomic status. Listen this week to hear all the numbers.

https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2023-065297/197777/Familial-Recurrence-of-Autism-Updates-From-the?autologincheck=redirected

https://pubmed.ncbi.nlm.nih.gov/38973707