Medical teams that provide on-site genetic counseling and new screening tools to outpatient clinics — to identify genetic causes of autism spectrum disorder such as fragile X syndrome — significantly improve diagnostic rates, a new study reports.
The study, “Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder,” was published in the journal Molecular Autism.
Fragile X syndrome is a genetic condition caused by changes in a gene known as FMR1. Fragile X is characterized by intellectual disabilities, behavioral and learning challenges, and various physical traits.
Many fragile X patients — 50–75% of males and up to 25% of females — exhibit autistic-like behaviors (autism spectrum disorder, or ASD) such as limitations in social interaction and communication, plus restrictive and repetitive patterns in behavior, activities, or interests.
ASD that is caused by chromosomal abnormalities like fragile X is called syndromic ASD.
While advances in diagnostic tools and genetic tests have improved over the years, in the authors’ view, “many patients still fail to be offered systematic investigations.”
To improve patients’ access to services, in 1998, a team based in the medical genetics clinic from the Necker-Enfants Malades University hospital in Paris, France, was established to visit 26 day-care (outpatient) hospitals and other specialized medical institutions in the greater Paris area.
Over the years, the team — it has grown from three original members to six today — has provided on-site clinical genetics consultation (risk assessment, education, and support for patients and families affected by genetic disorders), fragile X screening, metabolic testing, and new analytical tools to help identify genetic conditions that underlie ASD.
This study reports on the team’s impact on these on-site genetics consultations and how it has affected the rate of diagnosis in children and young adults with ASD.
A total of 502 patients from 26 institutions — all diagnosed with ASD — were included in the on-site program. Of these, there were 351 males and 151 females, with 34 patients below the age of 10, 194 patients between the ages of 11 and 20 years, 211 between 21 and 30 years, and 63 patients older than 30.
The team reviewed the laboratory tests of ASD patients which included screening for fragile X, metabolic tests, and cytogenetic analysis — all tests to identify chromosomal abnormalities.
They found that 312 of the 502 patients were not screened for fragile X . They then screened those 312 patients for fragile X and found four cases (1.3%).
In 2005, thanks to improvements in the chromosomal abnormalities test (array CGH), 388 patients were tested and of those, 34 (8.8%) were found to have pathogenic copy number variants (CNVs) — a different number of copies of a particular gene within an individual that are associated with diseases caused by gene deletions or duplications.
Then, in 2014, direct sequencing of the DNA (next-generation sequencing, or NGS) was added to the diagnostic toolkit. Sequencing of genes specifically associated with ASD and intellectual disabilities found 33 patients (23.4%) with pathological gene variations in 141 patients that were tested.
Overall, by implementing fragile X screening and array CGH testing, combined with NGS technology, the team “identified previously undiagnosed genetic conditions in 71 ASD children and young adults.”
This represented a significant increase in the number of diagnosed cases of syndromic ASD.
Consultations with parents of patients revealed that identifying an underlying genetic mechanism for their child’s ASD provided “relief” and it helped them understand and connect with other families facing similar challenges.
Based on their evaluation of the on-site program, the authors suggested, “that on-site clinical genetics consultations be considered in day-care hospitals and specialized institutions.”
To improve diagnostic rates, the authors recommend “first screening pathogenic CNVs and a limited number of disease genes in a much larger number of patients, especially those with syndromic ASD and intellectual disability.”