Table 3 Genetic testing strategies for neurodevelopmental disabilities.

Fragile X testing

Previously recommended as first-tier test for all males with NDDs, but low yield has resulted in reconsideration of this recommendation (https://www.nature.com/articles/gim2017146)

Uses polymerase chain reaction to detect CGG repeats in the FMR1 gene

>200 repeats cause Fragile X Syndrome, while 55–200 repeats is associated with Fragile X premutation-associated conditions (https://www.futuremedicine.com/doi/full/10.2217/fnl.14.11)

Chromosomal microarray

Detects genomic deletions and duplications as seen in 22q11.2 deletion syndrome or 15q11.2 duplication

Considered a first-tier test for NDDs with diagnostic yield of 10–20% (https://www.sciencedirect.com/science/article/pii/S0002929710002089)

Gene panel testing

Varies widely depending on the specific company

Detects a limited range of genetic variants known to be associated with NDDs

Whole exome sequencing

Uses next-generation sequencing to identify single base pair changes (single nucleotide variants) in gene-coding regions (exons)

Recent recommendations to include as first- or second-tier test for NDDs with diagnostic yields up to ~50% in most severely affected patients⁸⁰.

Does not detect genomic deletions/duplications or repeat expansions

Whole genome sequencing

Uses next-generation sequencing to identify single base pair changes (single nucleotide variants) in both gene-coding regions (exons) and gene regulatory regions (introns)

Can detect genomic deletions/duplications, but not repeat expansions

Recent recommendations to include as first- or second-tier test for NDDs with diagnostic yields up to ~50% in most severely affected patients⁸⁰.

DNA methylation analysis

For a few NDDs such as Beckwith-Wiedemann, Prader-Willi, and Angelman syndromes, abnormal methylation patterns are causative (https://pubmed.ncbi.nlm.nih.gov/28818477/)

Usually only ordered when clinically suspected