Bamshad, M. J., Nickerson, D. A. & Chong, J. X. Mendelian gene discovery: fast and furious with no end in sight. Am. J. Hum. Genet. 105, 448–455 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boycott, K. M. et al. A diagnosis for all rare genetic diseases: the horizon and the next frontiers. Cell 177, 32–37 (2019).

Article  CAS  PubMed  Google Scholar 

Boycott, K. M., Azzariti, D. R., Hamosh, A. & Rehm, H. L. Seven years since the launch of the Matchmaker Exchange: the evolution of genomic matchmaking. Hum. Mutat. 43, 659–667 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Wilczewski, C. M. et al. Genotype first: clinical genomics research through a reverse phenotyping approach. Am. J. Hum. Genet 110, 3–12 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gargano, M. A. et al. The Human Phenotype Ontology in 2024: phenotypes around the world. Nucleic Acids Res. https://doi.org/10.1093/nar/gkad1005 (2023).

Carmody, L. C. et al. The Medical Action Ontology: a tool for annotating and analyzing treatments and clinical management of human disease. Med 4, 913.e3–927.e3 (2023).

Article  Google Scholar 

Danis, D. et al. Phenopacket-tools: building and validating GA4GH Phenopackets. PLoS ONE 18, e0285433 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ladewig, M. S. et al. GA4GH Phenopackets: a practical introduction. Adv. Genet. 4, 2200016 (2023).

Article  CAS  PubMed  Google Scholar 

Jacobsen, J. O. B. et al. The GA4GH Phenopacket schema defines a computable representation of clinical data. Nat. Biotechnol. 40, 817–820 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bick, D., Jones, M., Taylor, S. L., Taft, R. J. & Belmont, J. Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases. J. Med. Genet. 56, 783–791 (2019).

Article  PubMed  Google Scholar 

Australian Genomics Health Alliance Acute Care Flagship et al. Feasibility of ultra-rapid exome sequencing in critically ill infants and children with suspected monogenic conditions in the Australian Public Health Care System. JAMA 323, 2503–2511 (2020).

Article  Google Scholar 

Costain, G., Cohn, R. D., Scherer, S. W. & Marshall, C. R. Genome sequencing as a diagnostic test. CMAJ 193, E1626–E1629 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Costain, G. et al. Genome sequencing as a diagnostic test in children with unexplained medical complexity. JAMA Netw. Open 3, e2018109 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Haque, B. et al. Contemporary aetiologies of medical complexity in children: a cohort study. Arch. Dis. Child. 108, 147–149 (2023).

Article  PubMed  Google Scholar 

Costain, G., Chow, E. W., Ray, P. N. & Bassett, A. S. Caregiver and adult patient perspectives on the importance of a diagnosis of 22q11.2 deletion syndrome. J. Intellect. Disabil. Res. 56, 641–651 (2012).

Article  CAS  PubMed  Google Scholar 

Pena, L. D. M. et al. Contributions from medical geneticists in clinical trials of genetic therapies: a points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 25, 100831 (2023).

Article  PubMed  Google Scholar 

Gleeson, J. G. et al. Personalized antisense oligonucleotides ‘for free, for life’ - the n-Lorem Foundation. Nat. Med. 29, 1302–1303 (2023).

Article  CAS  PubMed  Google Scholar 

Fanos, J. H. New “first families”: the psychosocial impact of new genetic technologies. Genet. Med. 14, 189–190 (2012).

Article  PubMed  Google Scholar 

Lee, W. et al. Genome sequencing among children with medical complexity: what constitutes value from parents’ perspective? J. Genet. Couns. 31, 523–533 (2022).

Article  PubMed  Google Scholar 

Vandeborne, L., van Overbeeke, E., Dooms, M., De Beleyr, B. & Huys, I. Information needs of physicians regarding the diagnosis of rare diseases: a questionnaire-based study in Belgium. Orphanet J. Rare Dis. 14, 99 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Diskin, C. et al. Research priorities for children with neurological impairment and medical complexity in high-income countries. Dev. Med. Child Neurol. https://doi.org/10.1111/dmcn.15037 (2021).

Nelson, K. E. et al. Clinical characteristics of children with severe neurologic impairment: a scoping review. J. Hosp. Med. 18, 65–77 (2023).

Article  PubMed  Google Scholar 

Gill, P. J. et al. Patient, caregiver, and clinician participation in prioritization of research questions in pediatric hospital medicine. JAMA Netw. Open 5, e229085 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Jacquemont, S. et al. Genes To Mental Health (G2MH): a framework to map the combined effects of rare and common variants on dimensions of cognition and psychopathology. Am. J. Psychiatry 179, 189–203 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Commission on Novel Technologies for Neurodevelopmental Copy Number Variants. Neurodevelopmental copy-number variants: a roadmap to improving outcomes by uniting patient advocates, researchers, and clinicians for collective impact. Am. J. Hum. Genet. 109, 1353–1365 (2022).

Article  Google Scholar 

Hanly, C., Shah, H., Au, P. Y. B. & Murias, K. Description of neurodevelopmental phenotypes associated with 10 genetic neurodevelopmental disorders: a scoping review. Clin. Genet. 99, 335–346 (2021).

Article  CAS  PubMed  Google Scholar 

McTague, A. et al. Defining causal variants in rare epilepsies: an essential team effort between biomedical scientists, geneticists and epileptologists. Eur. J. Med. Genet. 65, 104531 (2022).

Article  CAS  PubMed  Google Scholar 

Perlman, P. et al. Support to caregivers who have received genetic information about neurodevelopmental and psychiatric vulnerability in their young children: a narrative review. Clin. Genet. 104, 163–173 (2023).

Article  CAS  PubMed  Google Scholar 

Baribeau, D. A. et al. Developmental implications of genetic testing for physical indications. Eur. J. Hum. Genet. 30, 1297–1300 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Altmuller, F. et al. Genotype and phenotype spectrum of NRAS germline variants. Eur. J. Hum. Genet. 25, 823–831 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Armour, C. M. & Allanson, J. E. Further delineation of cardio-facio-cutaneous syndrome: clinical features of 38 individuals with proven mutations. J. Med. Genet. 45, 249–254 (2008).

Article  CAS  PubMed  Google Scholar 

Bassett, A. S. et al. Clinical features of 78 adults with 22q11 deletion syndrome. Am. J. Med. Genet. A 138, 307–313 (2005).

Article  PubMed  PubMed Central  Google Scholar 

Fung, W. L. et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome. Genet. Med. 17, 599–609 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kapadia, R. K. & Bassett, A. S. Recognizing a common genetic syndrome: 22q11.2 deletion syndrome. CMAJ 178, 391–393 (2008).

Article  PubMed  PubMed Central  Google Scholar 

Kidd, S. A. et al. Fragile X syndrome: a review of associated medical problems. Pediatrics 134, 995–1005 (2014).

Article  PubMed  Google Scholar 

Korenberg, J. R. et al. Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc. Natl Acad. Sci. USA 91, 4997–5001 (1994).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mautner, V. F. et al. Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. J. Med. Genet. 47, 623–630 (2010).

Article  CAS  PubMed  Google Scholar 

Pasmant, E., Vidaud, M., Vidaud, D. & Wolkenstein, P. Neurofibromatosis type 1: from genotype to phenotype. J. Med. Genet. 49, 483–489 (2012).

Article  CAS  PubMed  Google Scholar 

Chung, W. K. et al. Genomic medicine implementation protocols in the PhenX Toolkit: tools for standardized data collection. Genet. Med. 23, 1783–1788 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Tan, T. Y. et al. Bi-allelic ADARB1 variants associated with microcephaly, intellectual disability, and seizures. Am. J. Hum. Genet. 106, 467–483 (2020).

Article  CAS  PubMed