Pachyonychia Congenita with Laryngeal Obstruction

Haber, Richard M.; Drummond, Derek

doi:10.1111/j.1525-1470.2011.01232.x

Cited by 10 publications

(21 citation statements)

References 11 publications

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“…In Krt6a/b −/− mice, the formation of large hyperplastic lesions on the dorsal posterior tongue (akin to oral leukokeratosis, a PC symptom) is thought to occlude the laryngeal space, impair feeding, and lead to early death due to starvation. Such laryngeal obstruction, although extremely rare, has been reported in pediatric PC patients carrying KRT6a mutations (Smith et al, 2005; Haber and Drummond, 2011) and infants suffering from oral leukokeratosis often have trouble breastfeeding (Leachman et al, 2005). …”

Section: Resultsmentioning

confidence: 99%

Keratin 16–Null Mice Develop Palmoplantar Keratoderma, a Hallmark Feature of Pachyonychia Congenita and Related Disorders

Lessard

Coulombe

2012

Journal of Investigative Dermatology

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Keratin 16 (KRT16 in human, Krt16 in mouse), a type I intermediate filament protein, is constitutively expressed in epithelial appendages and is induced in the epidermis upon wounding and other stressors. Mutations altering the coding sequence of KRT16 cause Pachyonychia Congenita (PC), a rare autosomal dominant disorder characterized by hypertrophic nail dystrophy, oral leukokeratosis, and palmoplantar keratoderma (PPK). PPK associated with PC are extremely painful and compromise patient mobility, making them the most debilitating PC symptom. In this study, we show that, although inherited in a recessive fashion, the inactivation of Krt16 in mice consistently causes oral lesions as well as PPK-like hyperkeratotic calluses on Krt16−/− front and hind paws, which severely compromise the animals’ ability to walk. Our findings call into question the view that PC-related PPK arise exclusively as a gain-of-function on the account of dominantly acting mutated keratins, and highlight the key role of modifiers in the clinical heterogeneity of PC symptoms.

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Section: Resultsmentioning

confidence: 99%

Keratin 16–Null Mice Develop Palmoplantar Keratoderma, a Hallmark Feature of Pachyonychia Congenita and Related Disorders

Lessard

Coulombe

2012

Journal of Investigative Dermatology

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“…Laryngeal involvement with leukokeratosis of the larynx is a less reported manifestation of PC. It usually presents as hoarseness, stridor and very rarely as a life‐threatening respiratory distress . Hoarseness in association with PC was reported as early as 1935, and in more recent studies from data collated by the International Pachyonychia Congenita Research Registry (www.pachyonychia.org) .…”

Section: Discussionmentioning

confidence: 99%

“…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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“…Patients with PC who had oral leucokeratosis were more likely to report hoarseness of voice ( P < 0·001), suggesting that leucokeratosis may extend to the larynx to cause hoarseness. Three patients with PC with laryngeal involvement have been reported, with some patients requiring tracheostomies for life‐threatening respiratory insufficiency 11–13 …”

Section: Discussionmentioning

confidence: 99%

“…Three patients with PC with laryngeal involvement have been reported, with some patients requiring tracheostomies for life-threatening respiratory insufficiency. [11][12][13] The main limitation of this study is that the results may be subject to selection bias, as the IPCRR only includes patients who found the online registry or were referred to it by their physician; it is not a population-based sample. Strengths of this study include a validated questionnaire 8 and genotype analysis, which determined that all patients did indeed have PC with identified mutations, thus allowing these results to be the largest study comparing PC-K6a subjects with PC-K16.…”

Section: Discussionmentioning

confidence: 99%

Pachyonychia congenita patients with mutations in KRT6A have more extensive disease compared with patients who have mutations in KRT16

Spaunhurst

Hogendorf

Smith

et al. 2012

British Journal of Dermatology

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Pachyonychia Congenita with Laryngeal Obstruction

Cited by 10 publications

References 11 publications

Keratin 16–Null Mice Develop Palmoplantar Keratoderma, a Hallmark Feature of Pachyonychia Congenita and Related Disorders

Keratin 16–Null Mice Develop Palmoplantar Keratoderma, a Hallmark Feature of Pachyonychia Congenita and Related Disorders

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

Pachyonychia congenita patients with mutations in KRT6A have more extensive disease compared with patients who have mutations in KRT16

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