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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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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
Development and adaptive function in individuals with SCN2A-related disorders
  • The researchers aimed to describe the developmental and functional abilities of participants with SCN2A-related disorders based on different clinical groupings. Show More
  • The researchers studied 100 participants and assigned them to one of three groups: early onset SCN2A-related disorder, late onset SCN2A-related disorder, or a copy number variant (CNV) group that included SCN2A.
  • The early onset group (44 participants) was defined as having seizures that developed before 3 months old or developed between 3 months and 24 months (excluding a seizure type called epileptic spasms).
  • The late onset group (48 participants) included people who did not qualify for the early onset group.
  • The CNV group included 8 participants.
  • The researchers did not use variant function (loss of function or gain of function) to categorize SCN2A variants because not all variants have been functionally tested. But, they noted that for the variants that have been functionally tested, the participants with a gain of function variant were most often classified as early onset, and all participants in the early onset group had missense variants. Participants classified in the late onset group usually had variants that were considered to be loss of function. Of note, two participants with variants characterized as loss of function had seizures at birth.
  • Caregivers completed a comprehensive medical questionnaire and a medical interview either in-person or through a video call. Some caregivers provided additional medical records and completed a 1-year, follow-up medical questionnaire. The researchers also examined data from the Vineland Adaptive Behavior Scales-3 survey completed by Simons Searchlight participants.
  • Most participants (91 out of 100) had developmental delay and or intellectual disability, and 23 out of 80 participants over the age of 2 had an autism diagnosis, with a higher rate of people in the late onset group having autism.
  • Within the early onset group, the researchers observed three distinct phenotype sub-groups. 1) Early onset benign – self-limited infantile epilepsy that typically resolved by the age of 2, with no neurological symptoms after 2 years old. 2) Early onset intermediate – people with ongoing symptoms after 2 years, with one or more of the following: seizures, movement disorder, developmental delay/intellectual disability of up to moderate severity. 3) Early onset severe – people with severe to profound developmental impairments.
  • All participants in the early onset benign group attained their developmental milestones, whereas participants in the early onset intermediate group were often able to walk and run, but higher level skills were less often acquired, and participants in the early onset severe group had delays across all domains. Adaptive behavior scores followed a similar pattern – scores were highest (in the normal range) in the benign group, in a lower range in the intermediate group, and lowest in the severe group.
  • For the late onset group, people with seizures were less likely to be able to walk independently, and when studying this group, the researchers compared: 1) those without epilepsy, 2) those with late-onset epilepsy in childhood, and 3) those with late-onset epilepsy in mid-infancy.
  • Participants in the late onset group were more likely to experience a plateau or regression in development. This was less pronounced for participants without epilepsy. The presence of seizures had the highest association with the onset of a plateau or regression.
  • Many participants in the late onset group were able to sit and walk, and about 1 out of 5 were able to speak or follow 2-part commands. Most people without epilepsy were able to follow single commands. Adaptive behavior composite scores were similar among people in the late onset group (in the lower range), but scores were highest for participants without epilepsy.
  • This research will directly benefit families because it provides prognostic information in the absence of variant functional information. This research may also inform clinical care or the design of clinical studies. Show Less
Neurology 105, e213868 (2025)
Goad et al.
Full Article

SCN2A
2025

TAOK2 drives opposing cilia length deficits in 16p11.2 deletion and duplication carriers
  • The researchers used three 16p11.2 deletion induced pluripotent stem cell (iPSC) lines and three 16p11.2 duplication iPSC lines from Simons Searchlight participants to study if the gene TAOK2 is important for brain cell development. TAOK2 is located within the 16p11.2 region. Show More
  • 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 study, such as brain cells.
  • The researchers turned the iPSCs into brain cells (neurons).
  • Previous research showed that the gene TAOK2 is important for cell projections, also called cilia, which are important for cell movement and human development.
  • The researchers found that 16p11.2 deletion cells had longer cilia projections than 16p11.2 duplication cells, This difference might be due to the absence of TAOK2 in 16p11.2 deletion cells and the extra copy of TAOK2 in 16p11.2 duplication cells.
  • The researchers also looked at the downstream effects of having too little or too much TAOK2.
  • The researchers discussed potential future research, such as including more 16p11.2 deletion and duplication carriers and studying whether cilia are important in other cell types. Show Less
Stem Cell Reports 20, 102608 (2025)
Byeon et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2025

The Developmental Assessment of Social Communication Ability (DASCA): Initial creation and psychometric description
  • There was a need for more specific quantitative measures for social communication that are sensitive to the changes that a person undergoes over time. Show More
  • In this study, the researchers created the Developmental Assessment of Social Communication Ability (DASCA), a new survey developed as a clinical outcome tool for monitoring a person’s social and communication changes in response to treatment.
  • The researchers recruited through several studies, including 571 participants in Simons Searchlight.
  • The researchers used feedback from caregivers in the neurodevelopmental community to adjust their questions to effectively assess communication abilities for dependents in the neurodevelopmental community.
  • The researchers suggested that this new survey will be helpful in future clinical trials to measure the improvement in the social communication of children with neurodevelopmental disability. Show Less
Mol Autism 16, 52 (2025)
Kaat et al.
Full Article

All Genes
2025

Characterizing key correlates of sleep problems across rare neurodevelopmental genetic disorders
  • This study looked at sleep difficulties in rare genetic neurodevelopmental conditions. Show More
  • The researchers recruited through several patient advocacy organizations, including SYNGAP1, ADNP, CSNK2A1, GRIN2B, STXBP1, HIVEP2, SCN2A, and MED13L participants in Simons Searchlight.
  • Caregivers completed two surveys: the Children’s Sleep Habits Questionnaire and the Neurobehavioral Evaluation Tool. They also filled out a 7-day sleep diary.
  • Sleep issues were found in all the conditions studied. Participants in the SYNGAP1 group had the most disrupted sleep, as compared with the other genetic conditions, and the most problematic sleep areas were shorter time sleeping and a higher sleep anxiety.
  • The researchers suggested that people with SYNGAP1-related disorder might have more sleep disruption due to seizure activity.
  • Similar to other sleep research, the analysis found that emotion regulation challenges and depressive feelings were related to sleep initiation and maintenance issues. Emotional dysregulation likely makes it difficult for a child to fall asleep at night, but also to return to sleep on their own when they wake up during the night. Depressive feelings were also linked to feeling very sleepy in the morning and poor sleep quality.
  • Separation anxiety and not liking change to routine and/or rituals (insistence on sameness) were the biggest predictors of bedtime resistance. Children with sleep anxiety might have insistence on sameness behaviors to minimize their fears associated with sleep.
  • Anxiety and sensory sensitivities were also related to decreased sleep length, and they might contribute to insomnia symptoms.
  • The researchers suggested that sleep interventions for people with rare neurodevelopmental disorders should include the sleep disorder, the behavior, and emotional factors. This type of comprehensive approach is more likely to improve the quality of life for the person and their family. Show Less
J Autism Dev Disord 55, 4480-4491 (2025)
Baker et al.
Full Article

ADNP
CSNK2A1
GRIN2B
HIVEP2
MED13L
SCN2A
STXBP1
SYNGAP1
2025

Neurobehavioral signatures in overgrowth intellectual disability syndromes: Dissecting genotype-phenotype relationships in the PI3K-AKT-MTOR pathway
  • This research looked at genetic neurodevelopmental disorder (NDD) conditions that are associated with overgrowth features. Show More
  • The researchers included non-Simons Searchlight genetic conditions, MTOR- and PTEN-related disorders, and Simons Searchlight genetic conditions. This included 97 participants with CTNNB1, 65 participants with HIVEP2, 16 participants with PPP2R1A, 231 participants with PP2R5D, and 6 participants with WAC-related disorders.
  • CTNNB1, HIVEP2, PPP2R1A, PP2R5D, and WAC were chosen because they are NDD conditions that have features of overgrowth, and they overlap as being involved in a cell process called signaling.
  • The researchers studied the overgrowth features using both in-person assessments and remote surveys to learn if the different conditions have individual patterns of neurobehavioral features.
  • The researchers used CADD scores to study the relationship between missense variants in the genes and clinical medical features. CADD scores are a mathematical technique for understanding if a missense variant might be harmful. The NDD conditions showed a strong link between CADD scores and the results of a participant’s behavioral surveys. Sensory processing had the strongest positive correlation with CADD scores, and autism symptoms had the strongest negative correlation with CADD scores.
  • The researchers suggested that sensory profiles may be helpful for understanding genetic variants, but more research is needed to confirm this finding. Show Less
medRxiv Preprint, (2025)
Besterman et al.
Full Article

CTNNB1
HIVEP2
PP2R5D
PPP2R1A
WAC
2025

Age-aware genotype–phenotype architecture across 87 genetic neurodevelopmental disorders
  • The researchers aimed to create a comprehensive understanding of genetic neurodevelopmental disorders (NDDs) using data within Simons Searchlight. Show More
  • This study included 1,210 Simons Searchlight participants with problematic variants across 87 genetic variants.
  • The researchers used the medical history data within Simons Searchlight and assigned medical features to human phenotype ontology (HPO) terms. HPO terms are standardized terms and definitions used in the medical community to compare medical features across different clinics and research studies.
  • Across the genetic conditions, the researchers found growth-related abnormalities and medical features across body systems, including musculoskeletal, nervous, digestive, ocular, endocrine, and respiratory systems. Medical features in cardiovascular, genitourinary, and immune systems were less common. They noted that about 4 out of 10 participants had a copy number variant (CNV), and as a result, these medical features may be more representative for CNVs. But, in general, all of the genetic conditions had multi-system findings.
  • Even though there were common overlapping medical features across the genetic conditions, the researchers found that the timing and frequency differed among the genetic conditions. For example, earlier age of onset of seizures in one genetic condition or sleep issues being more common in some genetic conditions than others.
  • Some genetic conditions had more specific developmental profiles than others. For example, STXBP1, DYRK1A, and ASXL3 had unique developmental timing for seizures, low muscle tone, high muscle tone, and failure to thrive. This suggests that these different developmental profiles could be useful for NDD clinical developmental assessments. Other examples included: 1) participants with PP2R5D-related disorder had the earliest onset of larger than average head size (macrocephaly), 2) participants with SYNGAP1 genetic variants had absence seizures over six times earlier, 3) participants with STXBP1-related disorder had an early diagnosis of movement defects and seizures, and 4) participants with DYRK1A-related disorder had an early diagnosis of high muscle tone.
  • All the results from this analysis are available through an NDD-portal created by the researchers, which allows for visualization of the medical information for the genetic conditions included in the analysis: https://ndd-portal.lalresearchgroup.org/. Show Less
medRxiv Preprint, (2025)
Montanucci et al.
Full Article

All Genes
2025

Environmental modifiers of developmental outcomes in genetic epilepsy
  • To study how the environment might affect the severity of symptoms for people with rare genetic neurodevelopmental disorders (NDDs), the researchers used the data of 970 participants in Simons Searchlight. They studied the developmental outcomes for people with and without seizures. Show More
  • In this study, the researchers looked at 3 environmental categories: 1) pregnancy-related, including maternal use of alcohol or tobacco, supplementation with folic acid, prenatal vitamins, or iron during pregnancy, and preterm birth, 2) family-related and socioeconomic factors, such as parents’ marital status, education status, household income, and foster care, and 3) treatment-related factors, including treatment with sodium channel blockers and admission to an inpatient or intensive care setting.
  • Quality of life was different between participants with or without seizures, but adaptive function was more impaired for participants with seizures.
  • Pregnancy-related factors and socioeconomic factors were not identified as different between the two groups. Participants with seizures were more likely to be admitted to the intensive care unit, to be hospitalized, and to have received sodium channel blocker medications.
  • Treatment-related factors were more likely to be associated with a more negative quality of life and adaptive functioning. For example, hospitalization and treatment with sodium channel blockers were associated with a reported lower quality of life and lower adaptive functioning.
  • The researchers found that the association of sodium channel blockers with developmental outcomes was linked to gene-specific effects, duration of seizures, and the use of several seizure medications. In addition, a class of antiseizure treatments called GABAergic medications were linked to even lower quality of life and adaptive functioning as compared with the sodium channel blocker medications.
  • Socioeconomic factors, such as a parent’s education status and annual household income, had a positive association with quality of life.
  • The researchers suggested that the participant’s environment included in this analysis is very important for developmental outcomes, but that this research indicates the presence of more predictors of developmental outcomes than were included or identified in this study. In some genetic conditions (SCN2A, SLC6A1, and SYNGAP1) the genetic variant was the strongest factor determining developmental outcome. In other genetic conditions, there was more variability among participants, suggesting that there are other factors contributing to a person’s development. Show Less
medRxiv Preprint, (2025)
Bosselmann et al.
Full Article

All Genes
2025