Genetic Testing in Patients with Neurodevelopmental Disorders: Experience of 511 Patients at Cincinnati Children's Hospital Medical Center.
Xiaoli Du, Jennifer Elaine Glass, Stephanie Balow and 9 others
PMID 34773222WHAT IT FOUND
Testing 511 patients with neurodevelopmental disorders found a genetic diagnosis in 5.87%, mostly by first-tier microarray.
PTEN sequencing was negative in all 99 macrocephaly patients.
Key findings
01In 511 patients with neurodevelopmental disorders, the reflex genetic testing algorithm found a diagnosis in 5.87%, with 5.28% diagnosed by first-tier microarray.
02Microarray identified 30 pathogenic or likely pathogenic copy-number variants in 27 patients; the most common diagnoses were 15q13.3 microdeletion, 22q11.2 deletion, and 16p11.2 duplication.
03MECP2 sequencing was reflexed in 101 patients and found 2 pathogenic variants leading to Rett syndrome, while PTEN sequencing was negative in all 99 patients tested.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
Retrospective single-center chart review of tests that were already ordered, not a randomized trial or therapy study. The reflex algorithm meant many patients did not receive every test: Fragile X in 484 patients, MECP2 in 101, and PTEN in 99. Only 5.87% had a reportable diagnosis, and some copy-number variants were of uncertain significance or occurred in patients with more than one variant. The study did not separate intellectual disability or developmental delay from autism spectrum disorder when comparing its yield with previous reports. PTEN testing was limited to patients selected by macrocephaly and was negative in all 99 tested. Most patients were under 5 years old, although ages ranged from 3 months to 35 years. The paper reports genetic test results, not whether testing changed therapy or patient outcomes.
The easy way to misread this
Do not conclude that a negative genetic panel rules out a genetic cause. Only 5.87% of 511 patients had a reportable diagnosis, and some variants were of uncertain significance.