Phenome-wide profiling identifies genotype-phenotype associations in Phelan-McDermid syndrome using family-sourced data from an international registry.
Rui Yin, Maxime Wack, Claire Hassen-Khodja and 10 others
PMID 39350236WHAT IT FOUND
Children with larger 22q13 deletions in Phelan-McDermid syndrome had more severe motor delays, feeding problems, and medical issues like kidney defects.
However, they showed less verbal speech, self-care, and social interaction. They were also less likely to have autism or ADHD diagnoses than those with smaller deletions.
Key findings
01Larger deletions were strongly associated with delayed gross motor milestones, hypotonia, and feeding difficulties.
02Larger deletions were associated with reduced verbal speech, self-help skills, and social interaction.
03Individuals with larger deletions were less likely to be diagnosed with autism and ADHD compared to those with smaller deletions.
STILL TO COME
How it was doneWhat they foundWhat it means for PTsWhat it means for OTsWhat it means for SLPs
Read the rest of this summary
You get three full summaries a month, free, and we do not ask for a card. Search, the TL;DRs and your library stay unlimited either way.
What it does not show
Data were family-reported and retrospective, raising the possibility of recall bias and errors in medical terminology. The study population was predominantly White and less ethnically diverse than the general registry, limiting generalizability. Deletion size was used as a proxy for gene dosage; the specific genes responsible for the phenotypes could not be identified. Three-quarters of the registry individuals were excluded due to missing genetic or phenotypic data. The lower prevalence of autism and ADHD in larger deletions may be due to 'masking' by severe disability rather than a true protective effect.
Declared interests
Funding was provided by the Patient-Centered Outcomes Research Institute (PCORI), the National Institutes of Health (NIH), and Amazon. The study utilized data from the Phelan-McDermid Syndrome Foundation (PMSF), a family-driven organization.
The easy way to misread this
Do not assume that a lower rate of autism or ADHD diagnoses in patients with large deletions means they are less affected behaviorally. The study suggests this finding may reflect the severity of disability masking these specific diagnoses, or that these conditions are more common in the milder phenotypes associated with SHANK3 point mutations.