Do the data really support ordering fragile X testing as a first-tier test without clinical features?

Abstract

PurposeCurrent guidelines recommend first-tier chromosome microarray analysis (CMA) and fragile X syndrome (FX) testing for males with isolated intellectual disabilities/learning delay (ID/LD) and autism spectrum disorders (ASDs).MethodsMales in our clinic with ID/LD or ASD (310) were analyzed for positive results from CMA and/or FX testing.ResultsCMA detected abnormalities in 29% of males with ID/LD and only 9% of males with ASD (including variants of uncertain significance and absence of heterozygosity). When males with ID/LD were tested for FX, the detection rate was 2.5% (2 of 80). Both patients had dysmorphic features and maternal family history. No males with ASD had positive FX test results.ConclusionsThe detection rate of CMA in males with isolated ID/LD in this study was higher than in the literature (10-20%). CMA results for males with ASD (9%) and FX testing for males with ID/LD (2.5%) overlap with the literature (7-10% and 2%, respectively). The yield of FX testing for patients with ASD was zero, which is close to that of the literature (0.5-2%). These results suggest that FX testing as a first-tier test may not be necessary, unless other criteria suggest FX.