NDD-Portal

Documentation – NDD-Portal

The NDD-Portal is an interactive resource that allows researchers and clinicians to explore, for each genetic neurodevelopmental disorder (NDD), the full spectrum of associated phenotypes along with their prevalence and age-dependent penetrance trajectories. The tool offers the following capabilities:

1. Explore the spectrum of phenotypes presented by individuals with each genetic NDD, including the percentage of affected individuals per phenotype.
2. Visualize age-specific penetrance trajectories (percentage of carriers who have developed the phenotype by each age) for more than 90 genetic NDDs.
3. Estimate remaining risk of developing selected phenotypes given a patient’s current age.

Dataset

The NDD-Portal is based on two resources:

1. Simons Searchlight lifetime dataset (version 13).
   Variants and individuals — From this dataset, we selected 1,365 individuals with variants in one of 80 genes or 13 recurrent CNVs associated with neurodevelopmental disorders. The total number of variants was 2,891, of which 2,048 (71%) were classified as pathogenic or likely pathogenic, and 312 (11%) as variants of uncertain significance (VUS). The remaining 524 (18%) had an unspecified variant or lacked classification.
   
   Phenotypes — We selected 175 disease-related phenotypes with recorded age of onset and relevance to neurodevelopmental disorders (NDDs). Two key phenotypes, Autism and Developmental Delay/Intellectual Disability (DD/ID), were not part of the lifetime survey and were therefore integrated using information from the Simons Searchlight previous diagnosis dataset. For this integration, we identified sub-phenotypes corresponding to Autism and DD/ID, as detailed in the documentation table. This approach approximated the presence or absence of Autism and DD/ID across the cohort despite survey limitations. SInce data about the onset of these two phenotypes were not available they these two phentoypes are not available in any onset-related visualisations.


2. CACNA1A systematic literature review (July 2025) – details and data integration are currently being finalized and will be added in an upcoming release.

Methods

Age-dependent cumulative penetrance estimations – Age-dependent cumulative penetrance curves show the proportion of variant carriers of each genetic NDD who have developed a given phenotype by each age. Analyses included only genotype–phenotype pairs assessed in at least 20 individuals, with an overall penetrance exceeding 1%. Kaplan–Meier estimators were used to model cumulative risk, and only phenotypes with sufficient sample size and defined onset were included.

About the NDD-Portal

The NDD-Portal is an interactive resource that allows researchers and clinicians to explore, for each genetic neurodevelopmental disorder (NDD), the full spectrum of associated phenotypes together with their prevalence and age-dependent penetrance trajectories. The tool offers the following capabilities:

1. Explore the spectrum of phenotypes presented by individuals with each genetic NDD and the percentage of individuals with each phenotype.
2. Visualize age-specific penetrance trajectories (percentage of carriers who have developed the phenotype by each age) for more than 90 genetic NDDs.
3. Estimate remaining risk of developing selected phenotypes given a patient’s current age.

For information on the data, software, and tools used in the portal, view our documentation page.

How to cite

If you use the NDD-Portal, please cite the publication .

• Montanucci L, Brünger T, Boßelmann C et al. Age‑aware genotype–phenotype architecture across 87 genetic neurodevelopmental disorders.

Data Sources and Ethical Oversight

All data on this site are fully de-identified and shown only in aggregate. The current dataset comes from Simons Searchlight (Project ID 15099.1) and has been reviewed and approved by Dr. Lal’s institutional review board (IRB HSC-MS-23-1129). We’re continuously expanding the platform and plan to add new datasets from patient registries, advocacy groups, and clinical research teams.

Contact Us

For questions and requests or any other feedback, please contact us at Dennis.Lal@cookschildren.org .