Pathophysiology of pachyonychia congenita‐associated palmoplantar keratoderma: new insights into skin epithelial homeostasis and avenues for treatment

Abstract Background Pachyonychia congenita (PC, OMIM #167200, #167210, #615726, #615728, and #615735) is a rare autosomal dominant disorder caused by keratin gene mutations in KRT6A,KRT6B,KRT6C,KRT16 or KRT17. It is characterized with nail dystrophy and palmoplantar keratoderma (PPK). The most prominent manifestation is plantar pain. This is a further unusual case of parental mosaicism in PC. Although very rare, germ cell mosaicism should be considered when providing genetic counselling for unaffected parents of a child with PC. Case presentation We report the case of a 5-year-old boy with thickening nails and oral leukokeratosis at birth. He began to develop palmoplantar keratoderma at 2 years old and his sister has similar clinical manifestation characterized with nail discoloration and thickening. A previously reported heterozygous mutation, p.Ile462Asn, was identified in KRT6A in the proband and his affected sister. SNaPshot sequencing revealed mosaicism at a level of 2.5% and 4.7% in DNA from blood and hair bulbs from the unaffected mother. HiSeq deep sequencing demonstrated low-grade mosaicism in the patient’s younger sister and parents. Conclusion These findings indicate the ability of WES and SNaPshot sequencing to detect low-frequency mosaic mutations. Although very rare, germinal mosaicism should be considered when genetic counseling is given to families with presumed spontaneous cases of PC.

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Novel keratin 16 mutations and protein expression studies in pachyonychia congenita type 1 and focal palmoplantar keratoderma

Experimental Dermatology ◽

10.1034/j.1600-0625.2000.009003170.x ◽

2000 ◽

Vol 9 (3) ◽

pp. 170-177 ◽

Cited By ~ 42

Author(s):

F. J. D. Smith ◽

M. P. Fisher ◽

E. Healy ◽

J. L. Rees ◽

J. M. Bonifas ◽

...

Keyword(s):

Protein Expression ◽

Palmoplantar Keratoderma ◽

Keratin 16 ◽

Expression Studies ◽

Pachyonychia Congenita

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A novel frameshift mutation in keratin 16 underlies pachyonychia congenita with focal palmoplantar keratoderma

British Journal of Dermatology ◽

10.1111/j.1365-2133.2011.10450.x ◽

2011 ◽

Vol 165 (5) ◽

pp. 1145-1147 ◽

Cited By ~ 3

Author(s):

L-H. Cao ◽

Y. Luo ◽

W. Wen ◽

W-L. Liu ◽

L. Jiang ◽

...

Keyword(s):

Frameshift Mutation ◽

Palmoplantar Keratoderma ◽

Keratin 16 ◽

Pachyonychia Congenita

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Mutation p.Leu128Pro in the 1A domain of K16 causes pachyonychia congenita with focal palmoplantar keratoderma in a Chinese family

European Journal of Pediatrics ◽

10.1007/s00431-013-2236-8 ◽

2013 ◽

Vol 173 (6) ◽

pp. 737-741 ◽

Cited By ~ 1

Author(s):

Limeng Dai ◽

Jun Wu ◽

Hong Guo ◽

Yangming Huang ◽

Kun Zhang ◽

...

Keyword(s):

Chinese Family ◽

Palmoplantar Keratoderma ◽

Pachyonychia Congenita

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Pachyonychia Congenita (K16) with Unusual Features and Good Response to Acitretin

Case Reports in Dermatology ◽

10.1159/000438920 ◽

2015 ◽

Vol 7 (2) ◽

pp. 220-226 ◽

Cited By ~ 6

Author(s):

Fahad Almutawa ◽

Thusanth Thusaringam ◽

Kevin Watters ◽

Tenzin Gayden ◽

Nada Jabado ◽

...

Keyword(s):

Exome Sequencing ◽

Correct Diagnosis ◽

Type I ◽

Palmoplantar Keratoderma ◽

Whole Exome ◽

Epidermolytic Hyperkeratosis ◽

Dominant Disease ◽

Knuckle Pads ◽

Pachyonychia Congenita

Background: Pachyonychia congenita (PC) is a rare autosomal dominant disease whose main clinical features include hypertrophic onychodystrophy and palmoplantar keratoderma. The new classification is based on genetic variants with mutations in keratin KRT6A, KRT6B, KRT6C, KRT16, KRT17, and an unknown mutation. Here, we present a case of PC with unusual clinical and histological features and a favorable response to oral acitretin. Case: A 49-year-old male presented with diffuse and striate palmoplantar keratoderma, thickened nails, knuckle pads, and pseudoainhum. Histology showed compact hyperkeratosis, prominent irregular acanthosis, and extensive epidermolytic hyperkeratosis, suggestive of Vörner's palmoplantar keratoderma. However, keratin 9 and 1 were not mutated, and full exome sequencing showed heterozygous missense mutation in type I keratin K16. Conclusion: To our knowledge, epidermolytic hyperkeratosis has not been previously described with PC. Our patient had an excellent response, maintained over the last 5 years, to a low dose of acitretin. We wish to emphasize the crucial role of whole exome sequencing in establishing the correct diagnosis.

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A clinico-epidemiological study of various keratinization disorders

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20202653 ◽

2020 ◽

Vol 6 (4) ◽

pp. 493

Author(s):

Bharti K. Patel ◽

Nilam K. Selot ◽

Neela V. Bhuptani ◽

Pooja R. Raja

Keyword(s):

Acanthosis Nigricans ◽

Psoriasis Vulgaris ◽

Care Center ◽

Tertiary Care ◽

Common Type ◽

Palmoplantar Keratoderma ◽

Female Ratio ◽

Pityriasis Rubra Pilaris ◽

Keratinization Disorders ◽

Pachyonychia Congenita

Background: There is a vast spectrum of disorders with basic defect in the process of keratinization. There are various associations (genetic, autoimmune and environmental) with different keratinization disorders. The aims and objectives of this study to study the epidemiology, clinical features and associations in various keratinization disorders. Methods: A retrospective observational study of 500 patients was done in a tertiary care center. Detailed history was taken and clinical examination was done. Investigations and skin biopsy were performed when needed.Results: In our study of 500 cases of keratinizing disorders, there were 269 (53.8%) cases of psoriasis, 132 (26.4%) cases of palmoplantar keratoderma, 22 (4%) cases of phrynoderma, 19 (3.8%) cases of ichthyosis, 13 (2.6%) cases of acanthosis nigricans, 11 (2.2%) cases of porokeratosis, 7 (1.4%) cases of Darier’s disease, 3 (0.6%) Cases of pityriasis rubra pilaris, 2 (0.4%) cases each of pachyonychia congenita and erythron keratoderma. The most common age group affected was 51-60 years (19.6%). Males to female ratio was 1.13:1. Chronic plaque psoriasis (43.51%) was the most common variant of psoriasis. Psoriasis vulgaris (75%) was the most common cause of erythroderma. Histopathological findings in all patients whose biopsy was taken was consistent with clinical diagnosis. Non trans gradient (97.75%) was the most common type of palmoplantar keratoderma. Ichthyosis vulgaris (47.38%) was the most common type of ichthyosis.Conclusions: Heredity plays an important role in keratinization disorders. Also, various comorbidities have been associated with different keratinization disorders. Hence, we need to look for these factors while evaluating the patients of keratinization disorders.

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