Year : 2008 | Volume
: 20 | Issue : 2 | Page : 60--64
R Asish1, Sunu Ramachandran2, Anita Balan1,
1 Department Oral Medicine and Radiology, Government Dental College, Thiruvananthapuram, India
2 Department Oral Medicine and Radiology, Pariyarum Dental College, Kannoor, India
TC 4 / 1709 (2), MRA-27 Keerthi Lane, Engineering College (P.O), Thiruvananthapuram-695016, Kerala
Pachyonychia congenita represents a group of rare, autosomal dominant keratin disorders with characteristic nail findings, abnormalities of the palmoplantar skin, pilosebaceous apparatus, oral and laryngeal mucosa and teeth. The main clinical characteristic that gives the condition its name is the abnormally thickened nails. A case with typical clinical features is discussed.
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Asish R, Ramachandran S, Balan A. Pachyonychia congenita.J Indian Acad Oral Med Radiol 2008;20:60-64
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Asish R, Ramachandran S, Balan A. Pachyonychia congenita. J Indian Acad Oral Med Radiol [serial online] 2008 [cited 2021 May 11 ];20:60-64
Available from: https://www.jiaomr.in/text.asp?2008/20/2/60/44367
Pachyonychia congenita (PC) represents a group of rare, autosomal dominant keratin disorders with characteristic nail findings, abnormalities of the palmoplantar skin, pilosebaceous apparatus, oral and laryngeal mucosa and teeth. The hallmark of PC is the hyperkeratosis of the nail bed, which leads to the distal elevation with increased transverse curvature of nail plate. This abnormality results in an omega or pince nail appearance. The nail plates also become friable and discolored. These findings are severe on thumbs, index fingers and toes.
PC is a rare disorder; about 300 cases have been reported so far. Major clinical types of PC are the Jadassohn - Lewandowsky type (PC-1), Jackson - Lawler type (PC-2), Shafer-Brunauer type (PC-3), PC-4. A case of PC-1 which reported to our department is presented.
A 6 year old child was referred from the dermatology clinic for white patches in the oral cavity to the Department of Oral Medicine and Radiology, GDC, Thiruvananthapuram. Patient had consulted the dermatologist for the evaluation of asymptomatic nail changes that was present from the first year of life.
She had slight burning sensation in mouth while taking hot and spicy foods for more than 6 months. There was history of spontaneous shedding and then subsequent regrowth of right fingernail at the age of 2. Medical, drug and family history were noncontributory. There was no history of natal or neonatal tooth, early loss of primary teeth, oral blisters or plantar pain. She consulted a dentist at the age of 3 for removal of badly decayed lower right back milk teeth, the post extraction period was uneventful.
General examination revealed a moderately built and nourished girl with normal posture and gait. On examination, the nails demonstrated hyperkeratosis that was associated with distal elevation and increased transverse curvature of the nail plate, which gave an omega appearance. The nail plates were thick and yellow brown in color. There was keratoderma of knees and erythematous papular lesions of skin [Figure 1],[Figure 4],[Figure 5].
Intraoral examination demonstrated a white non-scrapable keratotic lesion on tongue and accentuation of bite line of buccal mucosa [Figure 2],[Figure 3]. Angular chelitis was also evident.
Routine blood and urine examinations were within the normal limits. Diagnosis of PC was made based on clinical findings. Biopsy of the oral lesions was deferred considering its benign nature.
Pachyonychia congenita is a rare, form of hereditary genodermatoses affecting nails and other ectodermal tissues. ,,,, This is characterized by discoloration and thickening of nails which usually begins with in the first month of life. The main clinical characteristic that give the condition its name is the abnormally thickened nails (Pachy=thick; nychia=nails). The term Pachyonychia congenita tarda (PCT) has been suggested by Paller et al . for the late onset form of PC. ,, PC was originally described by Wilson in 1905. In 1906, Jadassohn Lewandowsky reported the association of the disorder with palmoplantar keratoderma and other ectodermal defects. ,
Both sexes are affected equally, no pattern of occurrence has been found as to ethnicity or nationality. Hypertrophy and yellowish brown discoloration of the nails, hyponychial hyperkeratosis is present at birth or becomes apparent at the first year of life. ,, Hyperkeratosis and hyperhydrosis of palm and soles, acral bulla, follicular keratosis and oral leukokeratosis is also seen early in life. ,, Oral lesions presents as thickened white or grayish-white plaques on the dorsum of tongue. Buccal mucosa and palate may also be affected.
PC is caused by genetic mutations in genes that encode keratin proteins specific to the epithelial tissues. , On an average of 50% of the off springs of an affected person will inherit the disorder. The possibility of transmission of the mutate copy of gene of PC is 50% for each pregnancy.
Munro was the first to propose the genetic defect in PC located to keratin gene cluster in chromosome 17 in 1994.  In his detailed biologic analysis in 1995, McLean revealed that PC was caused by mutation in encoding the epidermal keratinocyte keratins K6a, K6b, K16 or K17.  Jadassohn-Lewandowski type (PC-1) is affected by mutation in gene encoding keratin 6a (Protein K6a, gene KRT6a) or keratin 16 (Protein K16, gene KRT 16). ,,,,,,, Jackson-Lawler (PC-2) type is caused by mutation in keratin 6b (protein K6b, gene KRT 6b) or keratin 17 (protein K17, gene KRT 17). Cockayne expressed the opinion that presence of an additional factor (second genetic mutation) is necessary for the expression of disease. ,,
Four clinical subtypes of PC have been described so far. PC1, Jadassohn - Lewandowsky is the more frequent variant. , The nails are thickened and brownish with gray surface. All finger and toe nails are affected. The thickened finger nails may expand into periungal tissue causing paronychia. ,,, The skin lesions consist of follicular hyperkeratosis of face and extensor aspects of proximal portion of extremities. Circumscribed or diffuse hyperkeratosis of palm and soles, periodic development of blister, hyperhidrosis are other characteristic features. ,,, Oral cavity affected by leukokeratosis demonstrated as patchy white areas on tongue and buccal mucosa. ,,
PC2, Jackson-Lawler syndrome is less common variant, characterized by hypotrichosis, thickened nails, natal teeth and pilosebaceous cyst. ,, Oral leukokeratosis occurs less frequently in PC-2.
PC-3, Shafer-Brunauer type, angular chelitis and corneal dyskeratosis are the important features. PC-4 shows features of other types along with laryngeal involvement and mental retardation.
Molecular DNA analysis reveals deletion and substitution mutation and other mutation of keratin genes. ,,, Prenatal diagnosis can be done by chorionic villous sampling. , Oral biopsy confirms leukokeratosis.
The hyperkeratotic lesions of skin and oral mucosa show acanthosis, hyperorthokeratosis and parakeratosis. Premalignant changes are, however, not observed.
The electron microscopy shows thickened and clumped intermediate filaments and keratohyaline granules. The thick clusters of tonofilaments and keratohyaline granules were present in granular layer. The spinous layer tonofilaments are found at the periphery of cells. There are no features pathognomonic of the disease.
In babies, PC is misdiagnosed as candidosis. ,, The occasional detection of few candidal spores but no hyphae excludes onycomycosis.
Dyskeratosis congenita is a rare congenital x-linked recessive trait characterized by atrophy and reticulated pigmentation of skin, dystrophy of nails and oral leukoplakia and progressive pancytopenia, which usually appears in childhood. ,
The most striking feature the of skin is hyper or hypo pigmented macules or reticulated patches. Thinned, tapered, distorted and dystrophic nails are another characteristic finding. Shedding of nails occurs usually after the age of 5. ,,
Mucosal leukoplakia is commonly seen on buccal mucosa, tongue and oropharynx. Other mucosal sites are also affected like oesophagus, anus, vagina and glans penis. Hyperhidrosis of palms and soles, aplastic anaemia, splenomegaly and mental retardation are other manifestations. Malignant neoplasm of skin, mouth, rectum and cervix has been reported.
Hereditary benign bntraepithelial byskeratosis (HBID)
A rare autosomal dominant condition, usually present in early life with bulbar conjunctivitis and whitish oral lesions. ,, Oral lesions consist of soft, asymptomatic white folds and plaques of spongy mucosa. The commonly affected areas are buccal and labial mucosa, labial commissures, floor of the mouth and lateral aspect of tongue, gingiva and palate. ,,, Oral lesion are generally detected in first year of life. The condition is self-limiting and it requires no treatment.
White sponge nevus
It is an autosomal dominant condition and is due to a mutation in keratins 4 and 13. , The lesion clinically appeared as asymptomatic, deeply folded white or gray thickenings with spongy texture.
Intraoral lesion, affects bilaterally on buccal mucosa in the form of keratosis appears that early in the life. A variable degree of involvement of other mucosal sites esophagus, vulva and vaginal mucosa occurred while conjuctival mucosa is spared. ,,,,, There is no specific treatment for this particular condition as it is asymptomatic and no risk for malignant potential.
Oral leukokeratosis is not a pre-cancerous lesion and is usually asymptomatic. The lesion is usually discovered on routine oral examination. The superadded candidosis is managed by antifungal therapy.  Retinoids are used to help in the differentiation and protection of epithelial tissues. The dystrophic nails are treated with keratinolytic agents like salicylic acid. The severely affected nails are removed surgically. 
Advancements in delivery systems, availability of RNA reduction agents, gene slicing approaches may improve, make the ultimate goal of target gene correction of PC more feasible in future. ,,
Pachyonychia congenital (PC) a rare genetic disorder of autosomal dominant trait. The dentists often get consulted for the oral leukokeratosis usually present in PC. Awareness of its benign nature can alleviate the apprehension in patient.
|1||Andrews GC, Strumwasser S. Pachyonychia congenita. New York J Med 1929;29:747-9.|
|2||Barns FS. A case of generalized congenita keratoderma with unusual involvement of eyes, ears and nasal and buccal mucous membranes. J Cutan Dis 1915;33:255-60.|
|3||Bowden PE, Haley JL, Kansky A, Rothnagel JA, Jones DO, Turner RJ. Mutation of a type II keratin gene (K6a) in pachyonychia congenita. Nat Genet 1995;10:363-5.|
|4||Brain RT. Pachyonychia congenita with ectodermal defect. Proc Internat Cong Dermatol 1952;507-208.|
|5||Cannon AB. White nevus of the mucosa. Arch Dermatol Syph 1935;31:365.|
|6||Cockayne EA. Inherited abnormalities of the skin and appendages. London: Oxford University Press; 1933.|
|7||Curtis AC, Slaughter JC. The clinical diagnosis of dermatological lesions of face and oral cavity. Am J Orthod Oral Surg 1947;33:218.|
|8||Dahl PR, Daoud MS, Su WP. Jadassohn-Lewandowski syndrome (pachyonychia congenita). Semin Dermatol 1995;14:129-34.|
|9||Dawber RPR, Baran R, de Berker D. Disorders of nails. In: Champion RH, et al , editors. Rook/Wilkinson/Ebling: Textbook of dermatology. 6 th ed. Oxford: Blackwell; 1998. p. 2834.|
|10||Dawber RPR, Baran R. Disorders of nails. In: Champion RH, Burton JL, Ebling FJ, editors. Textbook of Dermatology. 5th ed. Oxford: Blackwell Scientific Publications; 1992. p. 2530-1. |
|11||Feinstein A, Friedman J, Schewach-Millet M. Pachyonychia congenita. J Am Acad Dermatol 1988;19:705-11.|
|12||Feng YG, Xiao SX, Ren XR, Wang WQ, Liu A, Pan M. Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts. Br J Dermatol 2003;148:452-5.|
|13||Franzot J, Kansky A, Kavcie S. Pachyonychia congenita (Jadassohn-Lewandowsky syndrome): A review of 14 cases in Slovenia. Dermatologica 1981;162:462-72.|
|14||Frithiof L, Banoczy J. White sponge nevus (leukodema exfoliativum mucosae oris): Ultrastructural observations. Oral Surg 1976;41:607-22.|
|15||Gorlin RJ, Chaudhry AP. Oral lesions accompanying pachyonychia congenital. Oral Surg 1958;11:541-4.|
|16||Hannaford RS, Stapleton K. Pachyonychia congenita tarda. Australas J Dermatol 2000;41:175-7.|
|17||Irvine AD, McLean WH. Human keratin disease: The increasing spectrum of disease and subtlety of the phenotype-genotype correlation. Br J Dermatol 1999;140:815-28.|
|18||Jackson AD, Lawler SD. Pachyonychia congenital: A report of six cases in one family. Ann Eugen 1951;16:142-6.|
|19||Jadassohn J, Lewandowsky F. Pachyonychia congenita. In: Neisser A, Jacobi E, editors. Inkonographia dermatologica. Baltimore, MD: Urban and Schwarzenberg; 1906. p. 29. |
|20||Jadassohn J, Lewandowsky F. Pachyonychia congenita, Keratosis disseminate circumscripta (follicularis). Tylomata. Leukokeratosis linguae. In: Jacob's Ikonographia Dermatologica. Vol 1. Berlin: Urban and Schwarzenberg; 1906. p. 29-30.|
|21||Jorgenson RJ, Levin LS. White sponge nevus. Arch Dermatol 1981;117:73-6.|
|22||Kansky A, Dolenc-Voljic M, Bowden PE. Mycological examination in Pachyonychia congenita. Acta Dermatoven APA 1998;7:135-8.|
|23||Kaspar RL. Challenges in developing therapies for rare diseases including pachyonychia congenita. J Investig Dermatol Symp Proc 2005;10:62-6.|
|24||Krajewska IA, Moore L, Brown JH. White sponge nevus presenting in the esophagus: Case report and literature review. Pathology 1992;24:112-5.|
|25||Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH, et al . Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005;10:3-17.|
|26||Lewin AS, Glazer PM, Milstone LM. Gene therapy for autosomal dominant disorders of keratin. J Investig Dermatol Symp Proc 2005;10:47-61.|
|27||Lucker GP, Steijlen PM. Pachyonychia congenita tarda. Clin Exp Dermatol 1995;20:226-9.|
|28||Maser ED. Oral manifestations of pachyonychia congenita: Report of a case. Oral Surg Oral Med Oral Pathol 1977;43:373-8.|
|29||McGinnis JP Jr, Turner J. Ultrastructure of white sponge nevus. Oral Surg Oral Med Oral Pathol 1975;40:644-51.|
|30||McKusick V. Mendelian inheritance in man. 11 th ed. Baltimore, MD: J Hopkins University Press; 1994.|
|31||McLean WH, Rugg EL, Lunny DP, Morley SM, Lane EB, Swensson O, et al . Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 1995;9:273-8.|
|32||Munro CS, Carter S, Bryce S, Hall M, Rees JL, Kunkeler L, et al . A gene for pachyonychia congenita is closely linked to the keratin gene cluster on 17q12-q21. J Med Genet 1994;31:675-8.|
|33||Murray FA. Four cases of hereditary hypertrophy of the nail bed associated with a history of erupted teeth at birth. Br J Dermatol 1921;33:409-11.|
|34||Paller AS, Moore JA, Scher R. Pachyonychia congenita tarda: A late-onset form of pachyonychia congenital. Arch Dermatol 1991;127:701-3.|
|35||Reed JW, Cashwell F, Klintworth GK. Corneal manifestations of hereditary benign intraepithelial dyskeratosis. Arch Ophthalmol 1979;97:297-300.|
|36||Richard G, De Laurenzi V, Didona B, Bale SJ, Compton JG. Keratin 13 point mutation underlines the hereditary mucosal disorder white sponge nevus. Nat Genet 1995;11:453-5.|
|37||Rugg E, Magee G, Wilson N, Brandrup F, Hamburger J, Lane E. Identification of two novel mutations in keratin 13 as the cause of white sponge nevus. Oral Dis 1999;5:321-4.|
|38||Sallmann, L Vo, Paton D. Hereditary benign intraepithelial dyskeratosis: I ocular manifestations. AMA Arch Ophthalmol 1960;63:421-9.|
|39||Shields CL, Shields JA, Eagle RC Jr. Hereditary benign intraepithelial dyskeratosis. Arch Ophthalmol 1987;105:422-3.|
|40||Smith FJ, McKusick VA, Nielsen K, Pfendner E, Uitto J, McLean WH. Cloning of multiple keratin 16 genes facilitate prenatal diagnosis of pachynychia congenita type I. Prenat Diag 1999;19:941-6.|
|41||Smith FJ, Fisher MP, Healy E, Rees JL, Bonifas JM, Epstein EH Jr, et al . Novel keratin 16 mutations and protein expression studies in pachyonychia congenita type 1 and focal palmoplantar keratoderma. Exp Dermatol 2000;9:170-7.|
|42||Stieglitz JB, Centerwall WR. Pachyonychia congenita (Jadassohn - Lewandowsky syndrome): A seventeen member, four generation pedigree with unusual respiratory and dental involvement. Am J Med Genet 1983;14:21-8.|
|43||Su WP, Chun SI, Hammond DE, Gordon H. Pachyonychia congenita: A clinical study of 12 cases and review of the literature. Pediatar Dermatol 1990;7:33-8.|
|44||Takayama M, Okuyama R, Sasaki Y, Ohura T, Tagami H, Aiba S. Alleviation of the plantar discomfort caused by pachyonychia congenita with topical applications of aluminum chloride and salicylic acid ointments. J Dermatol 2005;211:302.|
|45||Terrinoni A, Smith FJ, Didona B, Canzona F, Paradisi M, Huber M, et al . Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita. J Invest Dermatol 2001;117:1391-6. |
|46||Thomsen RJ, Zuehlke RL, Beckman BI. Pachyonychia congenita: Surgical management of the nail changes. J Dermatol Surg Oncol 1982;8:24-8.|
|47||van Steensel MA, Koedam MI, Swinkels OQ, Rietveld F, Steijlen PM. Woolly hair, premature loss of teeth nail dystrophy, acral hyperkeratosis and facial abnormalities: Possible new syndrome in a Dutch kindred. Br J Dermatol 2001;145:157-61.|
|48||Ward KM, Cook-Bolden FE, Christiano AM, Celebi JT. Identification of a recurrent mutation in keratin 6a in a patient with overlapping clinical features of pachyonychia congenita types 1 and 2. Clin Exp Dermatol 2003;28:434-6.|
|49||Witkop CJ Jr, Shankle CH, Graham JB, Murray MR, Rucknagel DL, Byerly BH. Hereditary benign intraepithelial dyskeratosis: II, Oral manifestations and hereditary transmission. Arch Path 1960;70:696-711.|
|50||Witkop CJ Jr, Gorlin RJ. Four hereditary mucosal syndromes. Arch Dermat 1961;84:762-71.|
|51||Xiao SX, Feng YG, Ren XR, Tan SS, Li L, Wang JM, et al . A novel mutation in the second half of the keratin 17 1A domain in a large pedigree with delayed-onset pachyonychia congenita type 2. J Invest Dermatol 2004;122:892-5. |
|52||Young LL, Lenox JA. Pachyonychia congenita: A long-term evaluation of associated oral and dermal lesions. Oral Surg Oral Med Oral Pathol 1973;36:663-6.|
|53||Zegarelli EV, Everett FG, Kutscher AH, Gorman J, Kupferberg N. Familial white folded dysplasia of the mucous membranes. AMA Arch Dermatol 1959;80:59-65.|