announcement

Read about Simons Searchlight’s commitment to data privacy and security.

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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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.

Show More
Show Less

Search

  • Filter
  • Clear All
Genetic Condition
Year of Publication
142 Publications
MED13L-related disorder characterized by severe motor speech impairment
  • The researchers studied the speech, language, motor, cognitive, adaptive, and behavioral features of Simons Searchlight participants with MED13L-related syndrome. They also included in-person research data collected in 2022 at a MED13L Family and Research Conference. Show More
  • Language and speech are different - language is the meaning, structure, and the way in which a person uses words, whereas speech is the physical movement and coordination of the lips, tongue, and breathing to produce sound.
  • This study included 17 people from the in-person conference and 67 online participants with likely pathogenic and pathogenic MED13L variants.
  • All in-person participants had a motor speech disorder, such as childhood apraxia of speech, dysarthria, or both. Childhood apraxia of speech is a speech disorder caused by a problem with communication between the brain and the muscles used for speaking. Dysarthria is a speech disorder that results when the muscles used to speak become paralyzed or weakened. Everyone had severe impairment in receptive language (ability to understand language) and expressive language (ability to express yourself).
  • All in-person participants had intellectual disability, and when they were able to be measured, non-verbal IQ scores were higher than verbal IQ scores. They also had deficits in visual motor integration.
  • Most Simons Searchlight participants with MED13L-related syndrome reported having a language disorder (65 out of 67 people or 97 percent). One out of 3 children were minimally verbal or non-verbal after the age of 4.
  • In-person assessment of gross and fine motor deficits were comparable to what was reported through online data collection.
  • Motor speech disorders were common in the study participants, and this was considered to be consistent with a muscular/mechanical defect rather than a purely cognitive defect.
  • The researchers collected the medical history shared with Simons Searchlight. Commonly reported issues included low muscle tone in 50 out of 60 people (83 percent); gastrointestinal problems, including constipation, gastroesophageal reflux, and diarrhea in 34 out of 60 people (57 percent); and vision problems in 43 out of 60 people (72 percent). About 1 in 3 people reported seizures (20 out of 65 people or 31 percent), and 63 out of 65 people (97 percent) reported some degree of cognitive impairment and a language disorder diagnosis. Some participants had autism spectrum disorder (28 out of 57 people or 49 percent) and attention-deficit/hyperactivity disorder (13 out of 60 people or 22 percent).
  • The researchers suggested that there might be a higher rate of germline mosaicism in the MED13L community. Germline mosaic is when a person’s egg cells or sperm cells carry the same genetic variant, but that person does not have that variant detected in blood.
  • The researchers also suggested that children with MED13L-related disorder might benefit from a referral to speech therapy to assess their needs. Show Less
J Neurodev Disord 17, 56 (2025)
Mitchel et al.
Full Article

MED13L
2025

Genetic modifiers and ascertainment drive variable expressivity of complex disorders
  • The researchers studied why people with the same genetic neurodevelopmental condition have a spectrum of medical features, and what genetic factors might result in someone having more medical issues than others. Show More
  • The researchers included data from Simons Searchlight 16p11.2 deletion and duplication participants, as well as other genetic registries with 16p12.1 deletion carriers. The researches compared the medical features between people with 16p11.2 deletions and 16p12.1 deletions.
  • In this study, almost all people with a 16p12.1 deletion inherited the variant from a parent (84 out of 90 people or 93 percent). But, most parents, siblings, and other carrier relatives had milder cognitive or psychiatric issues than the child who was first identified with the genetic diagnosis. The first person in a family diagnosed with a genetic condition is called the proband.
  • The researchers studied the medical features across 6 domains: intellectual disability/developmental delay and behavioral, psychiatric, nervous system, congenital, and growth/skeletal defects.
  • Probands had more medical features than their relatives carrying the same genetic variant, but these relatives had more features than people with no identified genetic variant in this study.
  • About one-third of probands (31 out of 99 or 31 percent) had additional, clinically relevant genetic variants. The researchers also found that clinical severity increased in people with additional variants. This suggests that additional secondary variants contribute to a person having more medical features than the carrier parent.
  • In this analysis, the researchers suggested that contributing factors to a person’s medical features included: 1) their primary diagnosed genetic condition, 2) additional genetic variants and their function, 3) medical features that are being studied and/or how the person with the genetic condition was identified, meaning if a person was identified through a particular study focused on autism, or developmental delays.
  • The researchers did not find any single secondary variant that accounted for all medical features in a person, which indicates that secondary variants modify the effects of the 16p12.1 deletion. The researchers suggested that treatments that consider the primary or first diagnosed genetic condition, as well as the second or other variants, might be beneficial for medical management. Show Less
Cell 188, 7065-7082.e17 (2025)
Jensen et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2025

Comparison of autism domains across thirty rare variant genotypes
  • The researchers investigated how likely it is to develop autism across individuals with: idiopathic autism (autism with no known genetic cause), monogenic conditions (a genetic variant affecting only one neurodevelopmental gene), copy number variant conditions (larger deletions or duplications that include several genes, also called CNV), and control participants (people with no developmental or genetic diagnosis). Show More
  • The researchers collected Social Communication Questionnaire (SCQ) data from multiple cohort studies to examine the differences and similarities across groups. The SCQ is used as a tool to assess autism features in large research cohorts. A score of 22 or higher identifies that a person should have a clinical evaluation of autism, meaning that the survey is not able to provide someone with an autism diagnosis.
  • Lifetime SCQ data from 364 participants in Simons Searchlight, 309 people across 15 monogenic conditions, and 55 people across 5 CNV conditions were combined with SCQ data from other research studies.
  • The likelihood of autism was higher across monogenic conditions, with people having greater impairment than those with CNV conditions. ADNP and DYRK1A with the highest prevalence of autism.
  • Subdomains of the survey, which included communication, social, and repetitive behaviors were evaluated to see if there were differences within the various genetic conditions. This review found that there were relative strengths for certain genetic communities, such as 1q21 duplication carriers and communication, 16p11.2 deletion carriers and social domains, and HNRNPH2-related syndrome carriers and repetitive behaviors. There were also relative challenges for certain communities, such as communication for people with STXBP1-related syndrome, social behaviors for people with SCN2A-related syndrome, and repetitive behaviors for people with ASXL3-related syndrome and 15q11.2 deletion carriers.
  • The researchers noted that in general, the variability of the SCQ subdomain scores were greater within the results of people with a particular genetic condition, as compared with across genetic conditions. This suggests that a rare neurodevelopmental genetic variant on its own cannot predict if someone is going to have autism, and other genetic or environmental factors likely play a role.
  • This work was supported in part by a SFARI grant. Show Less
EBioMedicine 112, 105521 (2025)
Ali et al.
Full Article

15q11.2 deletion
16p11.2 deletion
16p11.2 duplication
1q21.1 deletion
1q21.1 duplication
ADNP
ASXL3
CTNNB1
DYRK1A
GRIN2B
HIVEP2
HNRNPH2
MED13L
PACS1
PPP2R5D
SCN2A
SETBP1
SLC6A1
STXBP1
SYNGAP1
2025

Clinical characteristics, longitudinal adaptive functioning, and association with electroencephalogram activity in PPP2R5D-related neurodevelopmental disorder
  • The researchers used Simons Searchlight data in combination with data collected at clinics. This included data from 42 people with pathogenic/likely pathogenic PPP2R5D variants. Show More
  • Six Simons Searchlight surveys were included: Annual Medical History Survey, Vineland-3, Child Behavior Checklist, Social Responsiveness Scale Second Edition, Children’s Sleep Habits Questionnaire, and Quality of Life Inventory - Disability.
  • The data from Simons Searchlight showed that people with PPP2R5D-related syndrome had low adaptive functioning (with gains in functioning over time), behavioral challenges, high rate autism, and sleep issues. Caregivers often reported macrocephaly, hypotonia, developmental delay, global developmental delay, or intellectual disability. About half of people had seizures and reported clinical EEG findings.
  • Clinic evaluations confirmed macrocephaly and hypotonia, low cognitive levels, and motor difficulties.
  • Caregiver burden was measured through a survey and the researchers found that 80 percent (20 out of 25 caregivers) were at risk of burnout.
  • EEGs were conducted by the researchers and the results were compared with a survey called the Vineland-3. EEGs give a readout of brain activity through a set of different waves. These waves look different if a person is awake or asleep because the brain function is different during those times. Two waves that are important for being awake and alert are called the beta and gamma waves.
  • The researchers found that people with PPP2R5D-related syndrome who had more EEG beta waves had lower adaptive behavior scores on the Vineland-3 survey, more behavior challenges, and sleep difficulties. People with PPP2R5D-related syndrome who had more EEG gamma waves had lower Vineland-3 communication scores.
  • This research, along with some other research on EEGs, supports the use of EEG signatures as potential biomarkers for other medical features outside of seizure activity.
  • The researchers suggested that people with the p.Glu200Lys variant had milder medical features compared with people with other PPP2R5D variants. Show Less
Clin Genet 107, 34-43 (2025)
Sudnawa et al.
Full Article

PPP2R5D
2025

Copy number variants and the tangential expansion of the cerebral cortex
  • This study used brain imaging from several different genetic cohort studies to see if there was a relationship between cortical surface area and copy number variant genetic variation. The researchers also wanted to see if region-specific, cell-specific, and time-specific gene expression played roles in shaping the development of cortical surface area. Show More
  • Cortical surface area refers to the outer area of the brain region, which is called the cortex (also known as the cerebral cortex). This is the outermost layer of the left and right sides of the brain. During the process of brain development starting in utero, the brain develops folds and this results in more surface area of the brain structure. Abnormal development of the cortical surface area is linked to neurodevelopmental conditions.
  • The cortical surface area is part of the brain that is important for thinking, voluntary movements, language, reasoning, and perception.
  • The researchers used Simons VIP (Simons Searchlight from 2010-2014) MRI brain imaging data from people with 16p11.2 deletions and duplications, people with 1q21.1 deletions and duplications, and family members without deletions or duplications. The study also included MRI brain imaging data from other research groups.
  • The researchers found that people with 16p11.2 or 1q21.1 deletions or duplications had a smaller cortical surface area compared with people without these copy number variants. People with 16p11.2 or 1q21.1 deletions had a smaller cortical surface area compared with people with these duplications. Show Less
Nat Commun 16, 1697 (2025)
Liao et al.
Full Article

16p11.2 deletion
16p11.2 duplication
1q21.1 deletion
1q21.1 duplication
2025

Differential links in 16p11.2 deletion carriers reveal aberrant connections between large-scale networks
  • The researchers used imaging and survey data from 26 Simons Searchlight participants with a 16p11.2 deletion and 41 age-matched people without a genetic diagnosis to investigate the brain connectivity differences in each group. Show More
  • The researchers studied the different brain patterns that light up on the MRI, which is called functional connectivity.
  • People with a 16p11.2 deletion had different functional connectivity of the brain than people with no genetic diagnosis. One hot spot of activity in people with a 16p11.2 deletion was linked to the region of the brain needed for processing speech sounds, which is similar to findings in other research studies.
  • The researchers also found other patterns, such as the way the brain lights up differently for people with lower communication and social adaptive behaviors. Show Less
Cereb Cortex 35, bhae474 (2025)
Qureshi et al.
Full Article

16p11.2 deletion
2025

Direct pathway bias and altered striatal neurogenesis in human iPSC models of 16p11.2 CNVs: Evidence from single-cell and functional analyses
  • The researchers investigated how a specific brain pathway called a striatal circuit is changed in people with a 16p11.2 deletion or duplication. A striatal circuit controls motor movement and is influenced by thoughts, emotions, and personal motivations. Show More
  • The researchers used 3 16p11.2 deletion and 3 16p11.2 duplication induced pluripotent stem cells (iPSCs) from Simons Searchlight participants. The researchers turned the iPSCs into striatal brain cells in the lab.
  • The researchers found that striatal 16p11.2 deletion cells divided more often and took longer to divide than cells with no genetic condition, and that striatal 16p11.2 duplication cells divided less often and faster than cells with no genetic condition. The researchers suggested that these reciprocal features of the cells are consistent with what has been reported in humans with deletion carriers having a larger than average head size and duplication carriers having a smaller than average head size.
  • Even though the cells behaved differently when growing and dividing, the researchers found that these copy number variant striatal cells favored one subtype in both deletion and duplication carriers. This could explain why having a deletion or duplication can be linked to similar neurodevelopmental conditions, such as autism, intellectual disability, and ADHD. Show Less
bioRxiv Preprint, (2025)
Fjodorova et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2025