title: Pachyonychia congenita in pediatric patients: natural history, features, and impact.
abstract: IMPORTANCE Nail dystrophy in early childhood often suggests a diagnosis of pachyonychia congenita (PC). No previous investigation has focused on the early signs of PC and the natural course of the disease. OBJECTIVES To determine the course of pediatric PC, correlate the disease course with the clinical appearance and specific gene mutations, and assess the effect of pediatric PC on quality of life. DESIGN, SETTING, AND PARTICIPANTS One hundred one patients or families with genetically confirmed PC from the International Pachyonychia Congenita Research Registry who completed a survey on the general clinical features of PC and an auxiliary questionnaire on the clinical presentation and quality-of-life issues related to pediatric PC. EXPOSURE Individuals with pachyonychia congenita. MAIN OUTCOMES AND MEASURES Completion of both surveys. RESULTS At birth, toenail changes were present in 47.5% of patients; fingernail changes in 40.6%; and plantar keratoderma in 6.9%. By 5 years of age, these 3 key manifestations were found in 81.2%, 74.2%, and 75.3%, respectively, of individuals with genotype-confirmed PC. The correct diagnosis was made during the first year of life in 26.7% of patients despite the presence of toenail dystrophy in more than 65.3%. Clinical differences that distinguished PC subtypes included (1) later onset and less frequent occurrence of nail dystrophy and keratoderma in PC-K6b, PC-K6c, and PC-K16; (2) concurrent fingernail and toenail thickening in PC-K6a and PC-K17; (3) more palmar keratoderma in PC-K16; (4) cysts primarily in PC-K17 and follicular hyperkeratoses primarily in PC-K6a; (5) hoarseness and/or oral leukokeratoses in the first year of life most often in PC-K6a; and (6) natal teeth exclusively in PC-K17. Among pediatric patients, PC affected the social interactions and function of adolescents most profoundly. CONCLUSIONS AND RELEVANCE Among patients with a detectable mutation, PC manifests with nail thickening and plantar keratoderma before school age in more than three-quarters of affected children, allowing early diagnosis. The highly visible nail changes and painful plantar thickening exert a psychosocial effect on most affected adolescents. Phenotype-genotype correlations in children with PC validate the new classification based on the affected gene.
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Sonal
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Monica
authors.initials: M
authors.lastname: Boen
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois2Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Brandi
authors.initials: B
authors.lastname: Kenner-Bell
authors.affiliation: Pachyonychia Congenita Project, Salt Lake City, Utah.
authors.forename: Mary
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois2Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000523:psychology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007645:Keratoderma, Palmoplantar / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053549:Pachyonychia Congenita / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D011788:Quality of Life; D011795:Surveys and Questionnaires; D055815:Young Adult