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Publications

Date Revised: March 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 March 2026, Simons Searchlight has contributed to 139 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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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
139 Publications
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

Beyond the diagnosis: Evaluation of quality-of-life measures in representing the clinical characteristics of SLC6A1-related neurodevelopmental disorder
  • This study focused on the relationship between three quality of life surveys and the clinical characteristics that affect the quality of life within the SLC6A1 community. Show More
  • The researchers used data from 20 participants in the SLC6A1-NDD clinical trial readiness study conducted at UT Southwestern Medical Center and 32 participants from Simons Searchlight.
  • The three quality of life surveys included: 1) the Quality-of-Life Inventory-Disability for individuals with intellectual disabilities, 2) the Pediatric Quality-of-Life Inventory Family Impact Module for assessing the impact of a disease on caregivers, and 3) the Quality-of-Life Childhood Epilepsy for people with epilepsy. Higher scores on these surveys suggest a higher quality of life, and lower scores suggest a lower quality of life.
  • This study found that males tended to have lower quality of life scores on the Quality-of-Life Childhood Epilepsy survey (overall scores and the emotion and social subdomains), and on the Pediatric Quality-of-Life Inventory Family Impact Module survey (physical and health-related quality of life subdomains).
  • Having a higher medical burden due to SLC6A1 clinical features was linked to worse scores on the Quality-of-Life Inventory-Disability survey (leisure and independence subdomains), on the Quality-of-Life Childhood Epilepsy survey (total scores), and on the Pediatric Quality-of-Life Inventory Family Impact Module survey (worry subdomain).
  • The researchers suggested that families who received an early SLC6A1 diagnosis might have higher quality of life, meaning that they might benefit from targeted therapies, treatment options, and social support.
  • For all three surveys, lower quality of life scores were associated with an increase in autism severity scores and developmental regression.
  • Certain symptoms might have more of an impact on a family’s quality of life, such as sleeping challenges, gastrointestinal issues, seizure burden, irritability/aggression, and anxiety.
  • The researchers suggested that although a family’s quality of life might be affected by the medical features associated with SLC6A1-related disorder, quality of life stabilizes over time and does not continue to worsen post-diagnosis. Show Less
Pediatr Neurol 173, 98-106 (2025)
Kalvakuntla et al.
Full Article

SLC6A1
2025

Brief report: Differences in naturalistic attention to real-world scenes in adolescents with 16p.11.2 deletion
  • The goal of this research was to study the specific clinical manifestations in people with a 16p11.2 deletion. Show More
  • People with a 16p11.2 deletion have an increased rate of autism and autism-related traits.
  • The researchers did eye-tracking studies in 21 teenage and adult participants with a 16p11.2 deletion and 23 participants without a genetic condition. Participants with a 16p11.2 deletion were recruited from Simons Searchlight.
  • The researchers used a virtual reality headset to show the participants real-world scenes, with objects, people, or background scenery. The researchers created eye-tracking maps based on what the participant focused on.
  • The researchers found that sex, IQ, and autistic traits were not good predictors of what the participant focused on. Participants with a 16p11.2 deletion had less observing across each scene and fewer fixations. The researchers suggested studying younger participants with a 16p11.2 deletion to see if a more obvious pattern would emerge. Show Less
J Autism Dev Disord 54, 1078-1087 (2024)
Haskins et al.
Full Article

16p11.2 deletion
2024

Dysregulation of mTOR signaling mediates common neurite and migration defects in both idiopathic and 16p11.2 deletion autism neural precursor cells
  • The goal of this research was to find out if there are brain developmental similarities between people with autism that has a genetic cause and people with autism that has no identified genetic cause. Show More
  • Participants with autism that has no known genetic cause were invited to the study. The study also included Simons Searchlight participants with a 16p11.2 deletion. Biological samples were collected from all participants. Samples were also collected from participants’ siblings who did not have autism. Participants’ cells were turned into brain cells that could be studied in the laboratory.
  • The researchers found that the laboratory brain cells from participants with 16p11.2 deletion grew and moved differently than the laboratory brain cells from their siblings, who did not have the deletion. The 16p11.2 deletion cells were more similar to the cells from participants with autism that had no genetic cause. These findings suggest that autism might develop following a common developmental process. Analysis revealed that the mTOR pathway had the strongest overlap between the samples from people with 16p11.2 deletion syndrome and the samples from people with autism that had no known cause.
  • The researchers also found some differences between the 16p11.2 deletion cells and the cells from participants with autism that had no genetic cause. They thought that the differences might be due to the ability of the cells to respond to communication factors.
  • The researchers found that tight control of the cell communication process—not too much and not too little—is very important for brain development. Show Less
eLife 13, e82809 (2024)
Prem et al.
Full Article

16p11.2 deletion
2024