Many Stickler patients exhibit Pierre Robin sequence, a combination of features (cleft palate, glossoptosis, micrognathia) that can lead to feeding problems and difficulty breathing.89,90 On average, significantly more novel variants in ECM genes were observed in the AIS cohort compared with controls, suggesting that the polygenic accumulation of novel variants within potentially many ECM genes contributes to AIS risk. This evidence concerns the gene MMRN1 and cleft palate.