This retrospective chart review shows variable reporting of genetic diagnoses by different types of care providers, revealing a gap for optimal personalized care for individuals with ID. All care providers involved in the care must be aware of the genetic diagnosis. Electronic care file systems accessible to all care providers with harmonized coding will ensure consistent reporting of genetic diagnoses in ID care. Significant associations were found between availability of information on genetic etiology (including genetic testing and diagnoses) in care files and individual’s age, level of ID, and the legal representative’s relationship to the individual.

Genetic causes of the ID were reported in 90% of medical files, 39% of psychodiagnostic files, and 75% of files used by professional caregivers, although VUS or incorrectly described genetic information were mentioned as cause of the ID in some of these different care files, thus misinterpreting these ambiguous or uncertain genetic findings. This suggests that adequate documentation of a genetic diagnosis is not standard part of multidisciplinary ID care. Barriers for reporting genetic diagnoses to explain the ID in multidisciplinary care have been found to include lack of awareness of potential benefits, lack of communication and harmonization of coding, and difficulty interpreting the results [17]. It may imply that many individuals with ID miss out on disorder-specific medical care, psychological care, and support. This is unfortunate, as a genetic diagnosis can provide detailed information on the prognosis of the disorder, associated somatic and neuropsychiatric manifestations, and targets for prevention, treatment, and management. It is also important for unaffected family members who might be at risk of passing on a genetic condition to their future children. As it may have impact on all life domains, awareness of all types of HCPs involved is necessitated to improve care [18].

Surprisingly, not all physicians who were involved in the care team had a reported genetic diagnosis in their medical files, while it was mentioned in one of the other care files, although not verified due to absence of a letter of a clinical geneticist. Coordinating physicians should have direct access to the genetic test results, which means they could inform and update the multidisciplinary team to enable personalized and disorder-specific care, and refer to expert centers where available. From a medical perspective, this may include each body system, including epilepsy management [19], tumor screening [15], prevention for sensitivity to obesity [20] and movement disorders [21], for which a dietician, physiotherapist, or occupational therapist should be involved as well. Without knowledge on the etiology, physicians will not identify and refer candidates who may benefit from disorder-specific care, including condition-specific guidelines or targeted treatments, such as indicated by the Treatable ID (Web) App [7].

Psychologists and behavioral therapists have a major role with regard to timely consultation of other experts, psychoeducation of care teams and families, treating complex behavioral manifestations, and providing information on appropriate behavioral interventions, guidance and mentoring, preventing frustration, crisis and overmedication [13]. Increasing knowledge on syndrome-specific behavioral manifestations is available [22, 23].

Caregivers are often the first to detect possible disorder-specific manifestations. Understanding the etiology of somatic and behavioral manifestations is of great importance for early signaling and to respond adequately. Especially in complex situations, comprehending the cause and support needs contributes to establishment of a shared concept and vision and multidisciplinary management. This may increase empowerment and anticipatory care planning.

For legal representatives who take care decisions for the affected individual, we found that individuals with close proximity of their legal representative such as first- and second-degree family member appeared to be more likely to receive genetic testing compared to those with a legal representative other than direct family, such as a professional. Family may be more engaged in health management, and may also directly benefit from a diagnosis by better understanding and acceptance, information on recurrence risks and prenatal diagnostic options, and prognostic value about whether someone could still live at home or need professional caregivers. Additional benefits for the affected individual or family members include supportive care, special education or tools, access to expertise centers and (peer) support groups, and financial and emotional support [24,25,26].

If current local and international (pediatric) guidelines were followed, one would expect that most individuals with ID had been referred to a clinical geneticist [27]. However, in our study, only in 40% of individuals with ID reports on genetic etiology were available in care files. A genetic diagnosis was identified in 34% of these individuals (which is 13% of the total sample), although official results were often not available in the electronic care file system. These results on current clinical practice demonstrate that genetic testing is underutilized, comparable to a previous study in Scotland that reported 41% of individuals with ID had genetic testing with a reported genetic cause for ID in 6% [28].

We found that more severe levels of ID, lower age, and close proximity of the legal representative’s relationship to the individual were associated with increased reporting of information on genetic etiology, indicating disparities in access to genetic testing. Notably, genetic testing in individuals with ID might differ throughout countries and cultures. Since European countries such as the Netherlands have a high standard with regard to easy and paid access to medical care, the care gap may be expected to be even greater in other countries. In the Netherlands, physicians can order specific genetic testing, such as microarrays or gene panels. In addition to paying a monthly premium for health insurance, there is an annual deductible that individuals must meet before their insurance covers certain healthcare costs. Genetic testing falls under this own contribution, but when it is met (which is often the case with this patient population), these costs are covered by the health insurance.

Factors associated with availability of information on genetic etiology in files may indicate both a reporting and diagnostic care gap. Individuals with a higher age appeared to be less likely to have reported information on receiving genetic testing and diagnosis. Our results confirm previous findings that a genetic diagnosis is lacking in many adults [29, 30], possibly including reasons such as less relevance to parents of affected adults in terms of recurrence risk. On the other hand, one could argue that older individuals would have a higher chance of having information on genetic etiology available, as they have had more time to be tested. As the largest population comprises adults, of which the majority did not receive a genetic diagnosis, these might thus miss out on personalized care.

Furthermore, individuals with mild ID appeared to be less likely to have reported information on genetic testing and diagnosis compared to those with moderate, severe or profound ID, possibly due to HCPs being less likely to consider genetic testing for mild ID and due to the fact that there seems to be more knowledge about the genetic causes associated with greater disability. On the other hand, many genetic syndromes show great heterogeneity regarding the level of intellectual functioning, with individuals with no or mild ID possibly being underrepresented and missing a diagnosis. Those with mild ID might thus more frequently miss out on disorder-specific care and interventions, underlining the need of awareness and guidelines.

Several barriers for the integration of genetic diagnoses into ID care may exist, including lack of parents for trio exome sequencing, financial issues, and lack of motivation by HCPs [31]. Practical barriers mentioned by physicians in previous research include lack of capacity or unavailability of consent by caregivers, burden and distress, unacknowledging benefits and skepticism about clinical utility especially in adults, and a lack of training resulting in difficulty interpreting and explaining genetic test [17, 28].

To overcome barriers and contributors to care gaps to identify individuals with ID at risk for underdiagnosis and undertreatment of genetic disorders, recommendations are provided in Table 5. Care organizations should connect with regional clinical genetic centers to reduce the referral threshold and diagnostic delay, for broader implementation of frontline tests (e.g., microarray and exome sequencing), for reassessment of whether additional testing might be of diagnostic benefit, and for reanalysis of VUS in genes for which functional tests are available. This may include episignatures which could provide conclusive findings for around 70 known ID syndromes as these have been considered highly sensitive, and specific DNA methylation biomarkers [32]. Education for affected individuals, families, caregivers, (professional) legal representatives, and all types of HCPs on both the importance of genetic testing and the genetic diagnosis may increase awareness and empowerment, and improve quality of multidisciplinary personalized care [33,34,35]. Adult care, which has usually been variable and fragmented, has greatly improved, advocating for holistic expert care worldwide.

Pediatric guidelines should be extended to adults, since implications of a diagnosis are important for the adult population as well. Individuals with no or borderline ID could also have a genetic disorder, as many genetic syndromes show a great heterogeneity within the disorder, which also requires special attention in psychiatric care. An update on current diagnostic guidelines including genetic testing and counseling in psychiatry has been proposed [36]. Awareness on factors that contribute to a diagnostic care gap should be increased to prevent them from missing out on personalized treatments, management and screening.

Furthermore, electronic care file systems should be improved for this patient population. Protocols should be established for harmonized coding of genetic diagnoses such as using OMIM and ORPHA code. Communication between HCPs should be facilitated by ICT systems, ensuring continuity, transferability and linkage to central relevant sites.

Expertise centers for rare diseases should (inter)nationally assemble, like the European Reference Network (ERN-)ITHACA (https://ern-ithaca.eu/), as these disorders collectively affect many individuals worldwide. These networks contribute to disorder-specific knowledge, including natural history, updating information with regard to the disorder and treatment options, setting up registries, and guidelines, and implementing these in national and regional care networks. This should be performed together with affected individuals and representatives, to also ensure availability of other resources for specific disorders, such as (peer) support groups [28].

Future research is necessary to examine why knowledge of genetic testing has not been fully implemented, to further identify barriers to personalized care. For instance, as the natural history of (ultra)rare disorders is often unknown, health care providers may question whether a genetic diagnosis really results in better care at present [37]. However, positive experiences in care and benefits for individuals should inspire all to enable and improve disorder-specific care.

This is the first study that elaborately investigated the integration of genetic diagnoses into multidisciplinary ID care in a large sample based on a sample size calculation. However, representativeness of the data may be affected by the consent procedure: bias might have occurred, since for individuals living within sheltered care facilities of the organization a standard questionnaire is included for providing consent. Selection bias with regard to symptoms, dysmorphisms, suspicion of syndromes, and comorbid features towards those who received genetic testing was not investigated. Moreover, negative genetic test results might not have been documented or (non-digital) information might be lost by switching care facilities or care providers, such as in the transition from pediatric to adult care. Due to privacy regulations, genetic results are usually only sent to the referring physician. Also, letters from clinical geneticists were often lacking in medical files, and genetic findings were sometimes unclear or incorrectly described by the care provider. Additional genetic variants of clinical relevance were not reported, although these have also been identified in genetic syndromes and ID [38]. As this was a retrospective study in a clinical setting, we could not examine the diagnostic yield of genetic testing [39].

We encountered difficulties related to inconsistent use of terminology and the lack of a uniform registration in the electronic care system where diagnoses could be found. Genetic disorders are often known by multiple names, possibly resulting in confusion and illustrating the importance of education amongst care providers.