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Publications

Date Revised: August 2026

Thank you to all the families for participating in Simons Searchlight. Through your involvement, we aim to assist researchers and geneticists worldwide in understanding genetic disorders affecting you or your family.

The research conducted using Simons Searchlight data has resulted in numerous published papers. These papers undergo a peer-review process, where other scientists assess and validate the research before publication in scientific journals. Additionally, some findings are shared via preprints, allowing rapid dissemination of information to the scientific community.

Many of the publications feature the name “Simons Variation in Individuals Project” (SimonsVIP), which was the original name of our research program, now known as Simons Searchlight.

The listed articles are organized from newest to oldest. You can explore publications by specific genetic conditions using the categories below.

As of August 2026, Simons Searchlight has contributed to 142 publications and preprints, and we will continue to summarize new publications.

For accessibility, the Simons Foundation encourages researchers to make their publications open access. If you cannot access a journal article, we recommend reaching out to the last author listed on the paper to request a copy.

Understanding Publication Reference Titles:

-The article title is followed by publication details, including where and when it was published.
– If there are more than three authors, we use “et al.” to represent additional contributors.
– Journals are referenced using shorthand names.

Disclaimer: Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication. In contrast, all other articles listed here have undergone review by fellow researchers to ensure quality and accuracy. While posting on medRxiv or bioRxiv allows researchers to share findings quickly, the final published results may differ after undergoing formal peer review for journal publication.

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Genetic Condition
Year of Publication
142 Publications
Parental experiences of receiving a rare genetic disease diagnosis for their child on diagnosis day
  • The researchers aimed to study the experiences of parents when receiving a rare genetic diagnosis for their child. The researchers wanted to better understand parents’ experiences to provide best practices for diagnosis delivery for healthcare providers. Show More
  • The researchers used Simons Searchlight to recruit for this study.
  • The recruited families with a child 18 years or younger who received their genetic diagnosis in the last 5 years.
  • 717 participants were included in this study, representing 229 rare diseases. About one-half of participants received their diagnosis in person and the rest received their diagnosis either by phone or telehealth.
  • Most often, a geneticist provided the diagnosis (41 percent), followed by genetic counselors (25 percent). 226 of the diagnoses were given by non-genetics providers. The researchers found an association between results being returned by non-genetics providers and the likelihood of parents responding that they would have liked something changed about their genetic results return.
  • Caregivers reported that the most important information during results return was quality of life, medical management, inheritance, and connecting with other families.
  • One-half of caregivers were provided support information at the time of diagnosis.
  • The most common emotions reported by caregivers at the time of their child’s genetic diagnosis were hopelessness, anxiety, sadness, confusion, and relief.
  • For genetic results return, about one-half of parents felt that there were areas that could have been improved. In general, areas for improvement included: (1) providing specific information on the diagnosis, (2) asking parents about their preferred method for disclosing results, (3) ensuring that all family members or support people can be present if desired, and (4) fostering an environment of compassion and empathy during the disclosure. Show Less
Am J Med Genet A 200, 67-76 (2026)
Bullock et al.
Full Article

All Genes
2026

Challenging behavior domains in individuals with neurodevelopmental genetic syndromes: The role of psychological features
  • The researchers studied problem behaviors, such as property destruction, aggression, elopement, conduct problems, and self-injury, in participants with neurodevelopmental genetic syndromes. Show More
  • The researchers recruited participants aged 3 to 45 with GRIN2B, CSNK2A1, HIVEP2, SCN2A, MED13L, ADNP, and STXBP1. The participants were recruited through Simons Searchlight and other patient advocacy foundations and non-profits.
  • The participants took five surveys that assessed problem behaviors, emotion regulation, anxiety, sensory sensitivity, and social communication.
  • The researchers found that emotion dysregulation was a strong predictor of aggression, conduct problems, and property destruction.
  • Lower levels of social communication was the strongest predictor of elopement and self-injury.
  • Different types of anxiety, such as worry or physiological, had their own associations with problem behaviors. Higher physiological anxiety, a racing heart, and being sweaty, flush, or shacky were strongly associated with elopement and aggression. Having lower worry was associated with elopement.
  • Lower levels of speech abilities was a predictor for conduct problems and elopement.
  • The researchers suggested that supporting a person through problem behaviors may require multi-faceted interventions for the child and the family, as there are links between the different behaviors. The individual’s needs, preferences, and risk of harm that may result from behaviors should be considered. Show Less
Am J Med Genet B Neuropsychiatr Genet 201, 52-63 (2026)
Ferguson et al.
Full Article

ADNP
CSNK2A1
GRIN2B
HIVEP2
MED13L
SCN2A
STXBP1
2026

A Prospective Natural History Study Protocol for Clinical Trial Readiness in Synaptic Disorders
  • The researchers created a protocol for prospective natural history data collection for STXBP1- and SYNGAP1-related disorders. A prospective natural history study is important for future therapies because it collects information from participants as they develop over time, and not only historical information. Show More
  • As genetic therapies have become more available to patient communities, understanding the natural history of rare genetic disorders has become a priority for many researchers.
  • The researchers combined in-person assessments with data from Simons Searchlight and the RARE-X registry.
  • This research is ongoing. The researchers will include 200 participants over time and complete assessments every 6 months at various clinical centers across the U.S.
  • The natural history study began in 2023, and 164 STXBP1 participants and 159 SYNGAP1 participants have been recruited thus far.
  • The majority (73 percent, 78 out of 107 people) with STXBP1-related disorder has had a seizure at any point in their lifetime. Age of onset ranged from day 0 of life to 11.7 years old, with an average age of onset of 2.5 months.
  • The majority (84 percent, 84 out of 100 people) with SYNGAP1-related disorder has had seizures at any point in their lifetime, with an average age of onset of 2.2 years.
  • The researchers suggested that parent-reported outcome measures, such as the data collected within Simons Searchlight, can offer insights into the participants that cannot be measured in a clinical setting. But, there were challenges to getting parents to complete the parent-reported surveys, even after discussion about the importance of completion with families.
  • The researchers aim to also identify biomarkers for these communities that can be used in clinical trials in the future. Show Less
medRxiv Preprint, (2026)
McKee et al.
Full Article

STXBP1
SYNGAP1
2026

Genotype-specific communication profiles in 79,518 individuals with neurodevelopmental disorders
  • The researchers looked at the communication abilities of participants in Simons Searchlight and participants in a related study called SPARK to see if there is a link between genetic conditions and development. Show More
  • Over 79,000 participants were included. All participants were 18 years or younger. Simons Searchlight participants had a genetic variant corresponding to one of 187 genetic conditions. SPARK participants had a diagnosis of autism, and some had a genetic diagnosis associated with their autism.
  • To study spoken language and non-spoken communication, such as pointing and gesturing, the researchers reviewed 10 caregiver-completed communication surveys that were available from both sets of participants.
  • 15 genetic conditions within Simons Searchlight were included: 16p11.2 deletion, 16p11.2 duplication, 1q21.1 deletion, 1q21.1 duplication, PPP2R5D, CTNNB1, SCN2A, STXBP1, GRIN2B, SLC6A1, CSNK2A1, SYNGAP1, MED13L, ASXL3, and SETBP1. The researchers looked for patterns of communication abilities in these genetic conditions. They then compared the results with findings from participants with 109 different genetic conditions in Simons Searchlight, as well as findings from SPARK participants with a known genetic diagnosis. Finally, they compared all their findings with the findings from a group of SPARK participants with autism but no known genetic diagnosis.
  • Each genetic condition had its own communication abilities across surveys. In general, participants with the 15 genetic conditions within Simons Searchlight had lower abilities on all five verbal communication scores compared with participants who had autism with no known genetic diagnosis. Specifically, they had lower expressive and receptive language, and a delayed timing of developing first words. They had higher scores on two surveys of nonverbal communication and social communication. Specifically, they had increased use of gesturing and expressing their own feelings appropriately.
  • Participants in one of the other 109 Simons Searchlight genetic groups and SPARK participants with a genetic diagnosis also had lower verbal and comprehension based abilities compared with the group of participants who had autism and no known genetic diagnosis. But, the Simons Searchlight participants had higher nonverbal abilities than the SPARK participants with a genetic diagnosis. This suggests that findings are not the same across all autism-related genetic conditions.
  • Within the 15 Simons Searchlight genetic conditions, participants with a 16p11.2 deletion, 16p11.2 duplication, or 1q21.1 deletion had the highest communication scores. They scored higher in some abilities than SPARK participants without a genetic condition.
  • Participants with SETBP1 or MED13L genetic variants were more likely to use gestures when they spoke than participants with an autism diagnosis without a genetic condition.
  • Participants with SLC6A1 had lower verbal communication and comprehension skills, but their nonverbal communication skills were similar to typical participants.
  • Participants with GRIN2B, SYNGAP1, SCN2A, ASXL3, and STXBP1 had low scores on communication surveys. Participants with SCN2A, ASXL3, and STXBP1 had the lowest scores.
  • Participants with a gene-related condition had lower communication abilities than participants who had copy number variants, including lower expressive and receptive abilities, lower likelihood of combining words into phrases, and lower use of phrases.
  • Participants with a 16p11.2 duplication, 16p11.2 deletion, CSNK2A1, SYNGAP1, or SCN2A were more likely to be using phrases as teenagers.
  • Finally, many participants with STXBP1 genetic variants tended to have a communication developmental plateau.
  • The findings of this study suggest that there are variable communication abilities in people with genetic neurodevelopmental disorders, with specific patterns that can be identified amongst the different groups.
  • Several groups had communication gains as participants got older, suggesting that speech and language therapy could be helpful across development. Show Less
medRxiv Preprint, (2026)
Hsu et al.
Full Article

16p11.2 deletion
16p11.2 duplication
1q21.1 deletion
1q21.1 duplication
All Genes
ASXL3
CSNK2A1
CTNNB1
GRIN2B
MED13L
PPP2R5D
SCN2A
SETBP1
SLC6A1
STXBP1
SYNGAP1
2026

Mechanisms of SCN2A loss of function do not predict presence or phenotype of epilepsy
  • Genetic variants in the SCN2A gene affect the function of the SCN2A protein in different ways. Show More
  • People with variants that result in a gain of the SCN2A protein usually have seizure onset before the age of 3 months, and their seizures can be managed with sodium channel-blocking medications. People with variants that result in a loss of the SCN2A protein usually develop seizures later, they may have autism, and sodium channel-blocking medications are not helpful for their seizures.
  • The researchers tested 15 different SCN2A genetic variants identified in participants with late-onset seizures or no seizures at all. The aim was to better understand the spectrum of genetic variants that are associated with the late-onset seizure condition.
  • The researchers selected participants in the SCN2A Natural History Study and compared their results with findings from participants with the same genetic variants in Simons Searchlight and in the published literature.
  • Functional testing of the following frameshift and protein truncating variants showed that these SCN2A variants had lost their function: p.Ser486Phefs*6, p.Phe537Argfs*3, p.Arg102*, p.Arg1235*, p.Trp1348*, p.Tyr1498del, and p.Arg1635*.
  • Similarly, specific missense variants had lost their SCN2A function: p.Arg119Ile, p.Arg937Cys, p.Met951Arg, and p.Leu1650Pro.
  • But, missense four variants, p.Val198Asp, p.Tyr428Cys, p.Arg1635Gln, and p.Ala1773Thr, were not found to lose their SCN2A function in the first test. This resulted in other types of testing for these genetic variants.
  • The researchers found that p.Val198Asp, p.Tyr428Cys, and p.Arg1635Gln all had a partial loss of function. The p.Ala1773Thr variant had a mixed function where in some tests, the SCN2A protein lost its function, and in other tests, it had a gain of SCN2A function.
  • In this study, 74 participants with these 15 SCN2A genetic variants had medical history available. More than half (47 of 74 or 64 percent) of participants had epilepsy, with an onset of 3 months to 5 years.
  • 33 of 74 participants (45 percent) had an autism diagnosis, and 62 of 65 participants (95 percent) had developmental delay or intellectual disability.
  • 27 of 33 participants (82 percent) had at least one developmental regression or developmental plateau.
  • Clinical features of the participants were categorized into three previously reported late-onset categories: 1) epilepsy-midinfancy, 2) epilepsy-childhood, and 3) intellectual disability and/or autism spectrum disorder without epilepsy. Five participants did not fit into any of the three categories. They did not have seizures, episodes of ataxia or paralysis of part of their body, or borderline or no intellectual disability.
  • The researchers found that the SCN2A genetic variant with loss of SCN2A function, partial loss of SCN2A function, or a mixed function did not reliably link to the participant clinical category. They cautioned that a person’s SCN2A-related medical features do not always indicate how their SCN2A protein is functioning. Show Less
Epilepsia Epub ahead of print, (2026)
Tan et al.
Full Article

SCN2A
2026

From QI-disability to QID-12: Creating a brief proxy-report measure of quality of life for children with intellectual disability
  • Quality of life surveys include questions about the physical, emotional, social, and personal development parts of a person’s life. Show More
  • The Quality of Life Inventory - Disability has 32 questions and is used in therapeutic trials for rare genetic neurodevelopmental conditions.
  • The researchers used a shortened version of the Quality of Life Inventory - Disability with only 12 questions and compared the responses with answers from the full version from participants in Simons Searchlight, The Kids Research Institute Australia datasets, and the Inchstone DEE Parents Speak survey dataset.
  • This study included 1,699 participants between the ages of 3 to 18 years old. Over half (953) were from Simons Searchlight.
  • Within Simons Searchlight, 88 percent of the participants walked independently.
  • The scores were similar between the full Quality of Life Inventory - Disability and the shorter version.
  • The researchers suggested that the Quality of Life Inventory - Disability with 12 questions provides an accurate picture of a dependent's overall quality of life.
  • The researchers suggested that this shorter version may be helpful in clinical settings or registries where participant burden is a concern. But, they stressed that the full version is still very important when a more comprehensive understanding of a dependent’s quality of life is needed. Show Less
Qual Life Res 35, 112 (2026)
Licari et al.
Full Article

All Genes
2026

Cell-type specific global reprogramming of the transcriptome and epigenome in induced neurons with the 16p11.2 neuropsychiatric CNVs
  • Mental health conditions, such as schizophrenia or anxiety, can be inherited, and researchers have been working to understand what factors may be inherited from family members. Show More
  • Since 16p11.2 deletions and 16p11.2 duplications have been linked to mental health conditions, the researchers used nine 16p11.2 deletion and five 16p11.2 duplication induced pluripotent stem cells (iPSCs) derived from Simons Searchlight participants. iPSCs are a special type of cells that can be turned into other body cells, making it easier to study parts of the body that are difficult to get samples of, such as brain cells.
  • These iPSCs were turned into different brain cells to learn which genes were turned on or off (also known as gene expression) that might lead to mental health conditions. The researchers also studied the presence of DNA methylation, a process where chemical tags are added to DNA to “silence” or turn off a genetic region.
  • Brain cells and neurons with a 16p11.2 deletion had genes within the 16p11.2 region that were less active. Whereas, brain cells and neurons with a 16p11.2 duplication had genes within the 16p11.2 region that were more active.
  • Importantly, genes outside the 16p11.2 region were also affected by changes in gene expression and DNA methylation, usually in the same direction (levels either went up in both deletions or duplications, or went down).
  • The PCSK9 gene did not follow this pattern. Gene expression in iPSCs was higher in 16p11.2 deletions and lower in 16p11.2 duplications. But, in neurons, gene expression was higher in both 16p11.2 deletions and 16p11.2 duplications. The researchers suggested that the PCSK9 gene could affect head size, brain development, and body size in people with a 16p11.2 variant.
  • To study this, the researchers used a fish model to study the PCSK9 gene, and they found that turning off the PCSK9 gene resulted in changes in embryonic and early brain development.
  • The researchers also found that in iPSCs and neurons, in both 16p11.2 deletions and 16p11.2 duplications, there was often more DNA methylation compared with cells without these variants, across many locations of DNA.
  • This work used advanced iPSC technology to help us better understand the bigger picture of what DNA in brain cells looks like in people with 16p11.2 deletions and 16p11.2 duplications. Show Less
Eur J Hum Genet Epub ahead of print, (2025)
Ward et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2025