Genotype-phenotype correlations with autism spectrum disorder-related traits in noonan syndrome and noonan syndrome with multiple lentigines: a cross-sectional study.

The study was cross-sectional and did not test any treatment, so it cannot show that a genotype causes behaviour problems or that a therapy will help. Rare variant groups were very small, especially NSML with seven children and RAF1-associated Noonan syndrome with six, so subgroup findings are uncertain. Children with a documented full-scale IQ below 70 were excluded, so the results may not apply to children with more significant cognitive impairment. Autism-related traits were mostly measured by parent-reported questionnaires, and formal clinical autism diagnoses were not obtained for most participants. The typically developing comparison group was recruited locally and had higher IQ scores than the study group, which may have widened behavioural differences. Some SRS-2 subscale scores have less empirical support than the total score, so subscale patterns should be read cautiously. Biochemical analyses were limited to PTPN11-associated Noonan syndrome, and the fold activation finding was exploratory.

The supplied text lists funding from NIH-funded studies and from Associazione Italiana per la Ricerca sul Cancro, the National Institute of Child Health and Human Development, the Neurofibromatosis Therapeutic Acceleration Program and the Stanford Maternal and Child Health Research Institute. It does not include an author conflict-of-interest declaration.

Do not conclude that PTPN11 or SOS1 variants cause autism or that a treatment will work for these children. The study compared groups at one time using parent-reported traits, did not test an intervention, and excluded children with IQ below 70, so it describes associations rather than treatment effects.