BG11 Palmoplantar keratoderma with mutations in filaggrin and desmoglein-1 genes

Abstract Hereditary palmoplantar keratoderma (PPK) has many forms, and genetic testing can help distinguish diagnoses. This case demonstrates a presentation of PPK with an altered phenotype caused by mutation in FLG. The patient was 23-year-old woman referred since the age 6 years. She reported dry skin on back her hands from infancy no other dermatological conditions. denied plantar pain except when there were fissures callus. There relevant past medical history, but significant family history individuals curly hair, sudden infant death (SID) two siblings. Physical examination revealed focal bilaterally, mild tongue leukokeratosis generally both legs. had palmar hyperlinearity, small calluses palms normal nails. declined biopsy. to cardiology rule out cardiomyopathy associated desmoplakin variant. unremarkable transthoracic echocardiography cardiac magnetic resonance imaging. Twelve-lead electrocardiography showed sinus rhythm biphasic T-wave V2 inverted V1. Clinically arrhythmogenic right ventricular (ARVC) ruled out; however, given SID PPK, panel for genes ARVC performed, which heterozygous variant uncertain significance MYBPC3 (p.Val639lle). did not explain patient’s PPK; therefore, performed. Next-generation sequencing identified DSG1 [c430A>T p.(Arg.144*)] pathogenic FLG [c2282_2285del p.(Ser761Cysfs*36)] more severe surface feet than one might expect interaction between variants known be Ichthyosis vulgaris is variants. Patients are less severely affected have reduced penetrance compared homozygotes. Meanwhile, keratosis palmoplantaris striata I (MIM148700). We hypothesize that coexistence may contribute extensive usually seen contributes our understanding value conditions describes unique presence multiple Further research required better understand pathogenesis.