Scott syndrome with novel compound heterozygous pathogenic variants in ANO6 and reduced thrombin generation

Scott syndrome is a recessively inherited, mild to moderate bleeding disorder attributed to variants in ANO6. To date very few cases have been reported worldwide, although we believe that it is under-reported due to a lack of platelet procoagulant activity screening in standard clinical platelet function assays. Here we present a patient with bleeding diathesis with two novel heterozygous variants in ANO6, little to no thrombin generation and reduced phosphatidylserine (PS) exposure which is indicative of Scott syndrome. This study highlights the importance of genetic screening as a first line of diagnosis for Scott syndrome followed by confirmatory thrombin generation studies. This study also provides sufficient support for the case of ANO6 as a definitive clinically relevant gene.