Pachyonychia Congenita (Jadassohn‐Lewandowsky syndrome): A seventeen‐member, four‐generation pedigree with unusual respiratory and dental involvement

Stieglitz, Jonathan; Centerwall, Willard R.; Opitz, John M.

doi:10.1002/ajmg.1320140105

Cited by 33 publications

(20 citation statements)

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“…It is notable that an affected member of this family died at 2 y of age because of respiratory infection. Although details of this case are not available, potentially fatal laryngeal involvement in childhood PC-1 has been reported on several occasions (Stieglitz and Centerwall, 1983;Wudy et al, 1995). The other 13 PC cases analyzed here were sporadic.…”

Section: Resultsmentioning

confidence: 79%

The Genetic Basis of Pachyonychia Congenita

Smith

Liao

Cassidy

et al. 2005

Journal of Investigative Dermatology Symposium Proceedings

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In 1994, the molecular basis of pachyonychia congenita (PC) was elucidated. Four keratin genes are associated with the major subtypes of PC: K6a or K16 defects cause PC-1; and mutations in K6b or K17 cause PC-2. Mutations in keratins, the epithelial-specific intermediate filament proteins, result in aberrant cytoskeletal networks which present clinically as a variety of epithelial fragility phenotypes. To date, mutations in 20 keratin genes are associated with human disorders. Here, we review the genetic basis of PC and report 30 new PC mutations. Of these, 25 mutations were found in PC-1 families and five mutations were identified in PC-2 kindreds. All mutations identified were heterozygous amino acid substitutions or small in-frame deletion mutations with the exception of an unusual mutation in a sporadic case of PC-1. The latter carried a 117 bp duplication resulting in a 39 amino acid insertion in the 2B domain of K6a. Also of note was mutation L388P in K17, which is the first genetic defect identified in the helix termination motif of this protein. Understanding the genetic basis of these disorders allows better counseling for patients and paves the way for therapy development.

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Section: Resultsmentioning

confidence: 79%

The Genetic Basis of Pachyonychia Congenita

Smith

Liao

Cassidy

et al. 2005

Journal of Investigative Dermatology Symposium Proceedings

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“…Laryngeal involvement is a less common feature. It might be asymptomatic but usually presents as hoarseness, stridor and, occasionally, as a life‐threatening respiratory distress . To date, few case reports of laryngeal involvement in patients with PC exist in the literature …”

Section: Summary Of Identified Mutations and Associated Mucosal Manifmentioning

confidence: 99%

Symptomatic mucosal involvement in pachyonychia congenita: challenges in infants and young children

et al. 2019

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Summary Background Pachyonychia congenita (PC) is a rare autosomal dominant genodermatosis caused by a mutation in any one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16 or KRT17). Characteristic features of PC are painful palmoplantar keratoderma, variable nail dystrophy, cysts, follicular hyperkeratosis and often oral leukokeratosis. Although oral leukokeratosis can go unnoticed, mucosal involvement of the oral cavity and upper airways can manifest with pain during feeding, hoarseness, stridor and, occasionally, life‐threatening obstruction. Objectives To characterize patients with PC with symptomatic mucosal involvement. Methods We present a case series of nine children with PC with symptomatic mucosal involvement, all with heterozygous mutations in KRT6A. Seven patients complained of painful feeding problems. Four patients were diagnosed with failure to thrive, three of whom required a feeding tube. Simple feeding solutions were beneficial in most cases. Seven patients had laryngeal involvement and one patient died at 4 years of age from acute laryngeal obstruction. Conclusions It is important for dermatologists and otolaryngologists to be aware that symptomatic mucosal involvement, and very rarely laryngeal obstruction, can occur in patients with PC. Usually simple feeding solutions may prevent complications and failure to thrive. What's already known about this topic? Pachyonychia congenita (PC) is a rare autosomal dominant genodermatosis due to a mutation in any one of five keratin genes. Symptomatic mucosal involvement is an important clinical feature of PC and appears to be more pronounced in KRT6A mutation carriers. Only leukokeratosis is frequently seen in PC and can be one of the earliest signs of disease. Laryngeal involvement is a less common feature. It might be symptomatic but usually presents as hoarseness, stridor and, occasionally, as a life‐threatening respiratory distress. What does this study add? In most cases of laryngeal involvement, there is no need for any intervention. Although pain and feeding difficulties are usually attributed to the oral leukokeratosis, they can be related to a phenomenon called ‘first bite syndrome’ (FBS). Symptomatic mucosal involvement with feeding difficulty is important but can be managed in most cases with simple feeding solutions (e.g. softer nipple with a larger hole, thicker formula and feeding with a syringe). Linked Comment: Youssefian and Vahidnezhad. Br J Dermatol 2020; 182:536–537.

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“…Because of its rarity, the condition has been difficult to characterize or investigate, and no controlled prospective clinical trials have been published using this patient population. Our understanding of the clinical and pathological features of the disorder has been based upon case reports, a few case series, and some excellent reviews that have attempted to unify the case report literature (Kumer, 1935;Moldenhauer and Ernst, 1968;Schonfeld, 1980;Franzot et al, 1981;Stieglitz and Centerwall, 1983;Sivasundram et al, 1985;Feinstein et al, 1988;Su et al, 1990;Paller et al, 1991;Dahl et al, 1995). A comprehensive bibliography of PC, complete with translations of non-English articles, is available at http://www.pachyonychia.org.…”

mentioning

confidence: 98%

Clinical and Pathological Features of Pachyonychia Congenita

Leachman

Kaspar²,

Fleckman

et al. 2005

Journal of Investigative Dermatology Symposium Proceedings

184

229

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Pachyonychia congenita (PC) is a rare genodermatosis affecting the nails, skin, oral mucosae, larynx, hair, and teeth. Pathogenic mutations in keratins K6a or K16 are associated with the PC-1 phenotype whereas K6b and K17 mutations are associated with the PC-2 phenotype. Analysis of clinical, pathological, and genetic data from the literature and two research registries reveal that >97% of PC cases exhibit fingernail and toenail thickening, and painful plantar keratoderma. Prospective evaluation of 57 PC patients from 41 families revealed variable clinical findings: hyperhidrosis (79%), oral leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma (60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%), coarse or twisted hair (26%), early primary tooth loss (14%), and presence of natal or prenatal teeth (2%). Stratification of these data by keratin mutation confirmed the increased incidence of cyst formation and natal teeth among PC-2 patients, although cysts were more commonly seen in PC-1 than previously reported (25%-33%). Previously unreported clinical features of PC include development of painful oral and nipple lesions during breastfeeding, copious production of waxy material in ears, and inability to walk without an ambulatory aid (50%). Possible pathogenic mechanisms are discussed with respect to the clinicopathologic and genetic correlations observed.

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Pachyonychia Congenita (Jadassohn‐Lewandowsky syndrome): A seventeen‐member, four‐generation pedigree with unusual respiratory and dental involvement

Cited by 33 publications

References 5 publications

The Genetic Basis of Pachyonychia Congenita

The Genetic Basis of Pachyonychia Congenita

Symptomatic mucosal involvement in pachyonychia congenita: challenges in infants and young children

Clinical and Pathological Features of Pachyonychia Congenita

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