Nature and Frequency of Genetic Abnormalities and Associated Phenotypes in a Cohort of Adults With Intellectual Disability

Overview

Intellectual disability (ID) is characterized by having an intelligence quotient (IQ) below 70 and substantial limitations in adaptive functioning across different domains, with the condition manifesting before the age of 18. Historically, it was noted that 25% of ID cases were attributed to acquired causes such as perinatal anoxia or infections, another 25% were linked to genetic factors, and the remaining 50% had an 'undetermined' cause. However, with advancements in genetic diagnosis, the proportion of cases with unknown causes is gradually diminishing, giving way to a greater understanding of genetic etiologies. The rarity of each of these causes of ID and the lack of specificity of most of the syndromes mean that it is often difficult to make an aetiological diagnosis. The objective of this study is to describe the nature and frequency of genetic abnomalties identified in adult patients with intellectual disability. This is a descriptive, retrospective and prospective study that aim to include 1000 patients across 10 centres aged over 20 years old on consultation between 2016 to 2025 who have been informed (where applicable, the guardian), who have not oppose to participate and who meet the inclusion and non-inclusion criteria. Each centre will include and increment a patient identification number for pseudonymisation of reports. A name correspondence table will be maintained by each center to establish a link between the research identifier and the participant's identity. Each table will be stored on each centre's secure server. The anonymized reports will be transmitted to the coordinating team through the secure Dispose platform, which will transfer all the participants' data to a REDCap APHP database. Descriptive statistic will be performed to count the number of patients with the same genetic syndrome. The age of onset of comorbidities and the proportion of each complication by syndromes will be calculated for all patient, including the means and median.

Intellectual disability (ID) is defined by the combination of an intelligence quotient (IQ) of less than 70 and significant limitations in adaptive functioning in various areas, with onset before the age of 18. Although common (2% of the population), ID is an extremely heterogeneous condition in terms of severity, associated additional disabilities and aetiologies. Until recently, it was reported that 25% of IDs had an acquired cause (perinatal anoxia, infection, etc.), 25% a genetic cause, and 50% an 'undetermined' cause; advances in genetic diagnosis are gradually reducing the latter proportion in favour of genetic aetiologies. The rarity of each of the genetic causes of ID and the lack of specificity of most of the syndromes mean that it is often difficult to make an aetiological diagnosis. This is a descriptive, retrospective and prospective study that aim to include 1000 patients across 10 centres aged over 20 years old on consultation between 2016 to 2025 who have been informed (where applicable, the guardian), who have not oppose to participate and who meet the inclusion and non-inclusion criteria. The first stage of the study will be the selection of patients' medical records by the participating centres. Patients aged over 20 with a proven intellectual disability who have been seen for consultations since 2016 will be identified on the basis of their electronic and/or paper medical records (retrospetive). Selection of the file includes a check of the elements present and missing from the file, using a clinical data collection grid and genetic results. If the data is available, the patient will then be selected. Once the files have been selected, the patient or, where appropriate, the guardian (if the patient is under guardianship) will be informed individually of the study and asked for their non opposition. For the prospective arm, patients over the age of 20 with a proven intellectual disability who are seen for routine care in the participating centres will be included. Each centre will increment a patient identification number for pseudonymisation of reports. A name correspondence table will be maintained by each center to establish a link between the research identifier and the participant's identity. Each table will be stored on each centre's secure server. The anonymized reports will be transmitted to the coordinating team through the secure Dispose platform, which will transfer all the participants' data to a REDCap APHP database. Descriptive statistic will be performed to count the number of patients with the same genetic syndrome. The age of onset of comorbidities and the percentage of each complication per syndrome will be calculated for all patients, including the means and median.