Twenty years of on-site clinical genetics consultations for people with ASD

Abstract

Despite advances in neurogenetics of autism spectrum disorders (ASD), many patients fail to be systematically investigated, owing to preconceived ideas, limited access to genetics facilities and inadequacy of consultations to children with behavioural problems. To improve access to services, we reversed the paradigm and delivered on-site genetics consultations to ASD children of Greater Paris day care hospitals and specialized institutions. Since 1998, an ambulatory medical genetics team has been in operation, offering on-site consultations and services to patients and relatives in their usual environment. Because the mobile medical genetics unit operates under the umbrella of a university hospital, service laboratories were shared, including molecular cytogenetics and next generation sequencing (NGS). For the past 20 years, 502 patients from 26 institutions benefited from on-site consultations and genetics services in their usual environment. Less than 1 % of parents declined the offer. Previously undiagnosed genetics conditions were recognized in 71 ASD children, including pathogenic CNV variants (34/388 : 8.8 ; de novo : 19, inherited : 4), Fragile X (4/312 : 1.3 %) and deleterious variants in disease causing genes (33/141 ; 23.4 % : de novo : 23 ; inherited : 10, including 5 X-linked and 5 compound heterozygote mutations). Brain MRI were possible in 347 patients and 42 % were considered abnormal (146/347). All diagnosed patients presented atypical/syndromic ASD with moderate to severe intellectual disability. Thanks to such flexible organisation, a considerable number of missed consultations were tracked and families first benefited from medical genetics services. Owing to constraints imposed by behavioural problems in ASD, we suggest considering on-site genetics services to implement standard of care and counteract the loss of chance to patients and relatives.