Clinical examination for hyperlinear palms to determine filaggrin genotype: a diagnostic test accuracy study.

BACKGROUND Palmar hyperlinearity is a feature of ichthyosis vulgaris, the monogenic skin disorder caused by FLG loss-of-function mutations. OBJECTIVE To investigate how well the presence or absence of hyperlinear palms (HLP) detect FLG genotype in children. METHODS STARD criteria are used to report this diagnostic accuracy study. Phenotype and genotype data (four most prevalent FLG null mutations) were obtained from a total of 3656 children in three studies: the UK CLOTHES trial (children 1-5 years with moderate-severe atopic eczema); UK BEEP trial (2-year-olds at high risk of developing atopic eczema); UK-Irish eczema case collection (0 to 16-year-olds with atopic eczema). All participants included in analyses of HLP as the index test and FLG genotype as the reference were of white European ancestry. RESULTS 32% of participants (1159/3656) had FLG null mutation(s) and 37% (1347/3656) had HLP. In 13% (464/3656) HLP was recorded as 'unsure' or not recorded. The sensitivity and specificity of HLP for detecting FLG mutations in each of the studies was: 67% (95% CI 55-78%) and 75% (67-82%) in CLOTHES; 46% (36-55%) and 89% (86-91%) in BEEP; 72% (68-75%) and 60% (57-62%) in the UK-Irish case collection. Positive and negative likelihood ratios were: 2.73 (1.95-3.81) and 0.44 (0.31-0.62) in CLOTHES; 4.02 (2.99-5.40) and 0.61 (0.52-0.73) in BEEP; 1.79 (1.66-1.93) and 0.47 (0.42-0.53) in the UK-Irish collection. DISCUSSION Trained observers were able to define palmar hyperlinearity in the majority (3191/3656, 87%) of cases. The presence of HLP is not a reliable sign to detect FLG mutations, but the absence of HLP excludes FLG null genotype with a reasonable degree of certainty. Registration This retrospective study was not pre-registered.