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Pachyonychia congenita 3(PC3)

MedGen UID:
811523
Concept ID:
C3714948
Disease or Syndrome
Synonyms: PC-K6a; PC3
 
Gene (location): KRT6A (12q13.13)
 
Monarch Initiative: MONDO:0014324
OMIM®: 615726

Disease characteristics

Excerpted from the GeneReview: Pachyonychia Congenita
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, painful palmoplantar keratoderma and blistering, oral leukokeratosis, pilosebaceous cysts (including steatocystoma and vellus hair cysts), palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities. [from GeneReviews]
Authors:
Frances JD Smith  |  C David Hansen  |  Peter R Hull, et. al.   view full author information

Additional description

From OMIM
Pachyonychia congenita (PC) is an autosomal dominant genodermatosis with the main clinical features of hypertrophic nail dystrophy, painful and highly debilitating plantar keratoderma, oral leukokeratosis, and a variety of epidermal cysts. Although the condition had previously been subdivided clinically into Jadassohn-Lewandowsky PC type 1 and Jackson-Lawler PC type 2, patients with PC were later found to have a mixed constellation of both types, leading to a classification of PC based on genotype (summary by Sybert, 2010; Eliason et al., 2012; McLean et al., 2011). For a discussion of genetic heterogeneity of pachyonychia congenita, see 167200. Historical Classification of Pachyonychia Congenita Gorlin et al. (1976) suggested that 2 distinct syndromes are subsumed under the designation pachyonychia congenita. PC type 1, the Jadassohn-Lewandowsky type, shows oral leukokeratosis. PC type 2, the Jackson-Lawler type, has natal teeth and epidermoid cysts (cylindromas), but no oral leukoplakia. Corneal dystrophy may be a feature exclusively of the Jackson-Lawler type. Smith et al. (1998) stated that PC type 2, in contrast to PC type 1, has minimal oral involvement and milder keratoderma, and multiple steatocystomas (184500) is a major clinical feature. Steatocystoma, also known as eruptive vellus cyst, is a cystic hamartoma lined by sebaceous ductal epithelium. On the basis of a study of 13 patients with PC type 1 or type 2, Terrinoni et al. (2001) concluded that the presence of pilosebaceous cysts following puberty is the best indicator of PC type 2; prepubescent patients are more difficult to classify due to the lack of cysts. Natal teeth are indicative of PC type 2, although their absence does not preclude the PC type 2 diagnosis.  http://www.omim.org/entry/615726

Clinical features

From HPO
Palmar hyperkeratosis
MedGen UID:
869284
Concept ID:
C4023710
Disease or Syndrome
Abnormal thickening of the skin localized to the palm of the hand.
Palmoplantar keratoderma
MedGen UID:
1635750
Concept ID:
C4551675
Disease or Syndrome
Abnormal thickening of the skin of the palms of the hands and the soles of the feet.
Gingivitis
MedGen UID:
4895
Concept ID:
C0017574
Disease or Syndrome
Inflammation of the gingiva.
Oral mucosa leukoplakia
MedGen UID:
9738
Concept ID:
C0023532
Neoplastic Process
A thickened white patch on the oral mucosa that cannot be rubbed off.
Furrowed tongue
MedGen UID:
21583
Concept ID:
C0040412
Anatomical Abnormality
Accentuation of the grooves on the dorsal surface of the tongue.
Chapped lip
MedGen UID:
603218
Concept ID:
C0424489
Finding
Cracking, fissuring, and peeling of the skin of the lips.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Phrynoderma
MedGen UID:
83101
Concept ID:
C0334013
Disease or Syndrome
A skin condition characterized by excessive development of keratin in hair follicles, resulting in rough, cone-shaped, elevated papules resulting from closure of hair follicles with a white plug of sebum.
Plantar hyperkeratosis
MedGen UID:
341658
Concept ID:
C1856954
Finding
Hyperkeratosis affecting the sole of the foot.
Onychogryposis of toenails
MedGen UID:
870241
Concept ID:
C4024679
Anatomical Abnormality
Thickened toenails.

Professional guidelines

PubMed

Koren A, Sprecher E, Reider E, Artzi O
Br J Dermatol 2020 Mar;182(3):671-677. Epub 2019 Sep 8 doi: 10.1111/bjd.18169. PMID: 31127950
Goldberg I, Fruchter D, Meilick A, Schwartz ME, Sprecher E
J Eur Acad Dermatol Venereol 2014 Mar;28(3):279-85. Epub 2013 Jan 30 doi: 10.1111/jdv.12098. PMID: 23363249
Gruber R, Edlinger M, Kaspar RL, Hansen CD, Leachman S, Milstone LM, Smith FJ, Sidoroff A, Fritsch PO, Schmuth M
J Am Acad Dermatol 2012 Jun;66(6):e193-9. Epub 2011 May 24 doi: 10.1016/j.jaad.2011.02.003. PMID: 21601946

Recent clinical studies

Etiology

Neale H, Schrandt S, Abbott BM, Austin J, Brand C, Camp K, Devenport K, Hall M, Isbell L, Miciano C, Pry S, Quinn P, Rittle J, Tenconi F, Terrell J, Weiss M, Zavitz S, Siegel M
Pediatr Dermatol 2023 Mar;40(2):250-257. Epub 2022 Nov 28 doi: 10.1111/pde.15199. PMID: 36443263
Samuelov L, Smith FJD, Hansen CD, Sprecher E
Br J Dermatol 2020 Mar;182(3):738-746. Epub 2020 Jan 14 doi: 10.1111/bjd.18794. PMID: 31823354
Forrest CE, Casey G, Mordaunt DA, Thompson EM, Gordon L
Pediatr Dermatol 2016 May;33(3):337-42. Epub 2016 Apr 4 doi: 10.1111/pde.12841. PMID: 27041546
van Steensel MAM, Coulombe PA, Kaspar RL, Milstone LM, McLean IWH, Roop DR, Smith FJD, Sprecher E, Schwartz ME
J Invest Dermatol 2014 Mar;134(3):588-591. doi: 10.1038/jid.2013.392. PMID: 24518109Free PMC Article
van Steensel MA, Koedam MI, Swinkels OQ, Rietveld F, Steijlen PM
Br J Dermatol 2001 Jul;145(1):157-61. doi: 10.1046/j.1365-2133.2001.04303.x. PMID: 11453928

Diagnosis

Tan Y, Ma DL
Indian J Pediatr 2024 Mar;91(3):300-301. Epub 2023 Jun 8 doi: 10.1007/s12098-023-04567-z. PMID: 37289311
Steele L, O'Toole EA
Br J Dermatol 2020 Mar;182(3):521-522. doi: 10.1111/bjd.18817. PMID: 32107781
Dessinioti C, Katsambas A, Antoniou C
Clin Dermatol 2014 May-Jun;32(3):397-408. Epub 2013 Nov 22 doi: 10.1016/j.clindermatol.2013.11.006. PMID: 24767187
Inamadar AC, Palit A
Indian J Dermatol Venereol Leprol 2012 May-Jun;78(3):271-8. doi: 10.4103/0378-6323.95441. PMID: 22565426
Hannaford RS, Stapleton K
Australas J Dermatol 2000 Aug;41(3):175-7. doi: 10.1046/j.1440-0960.2000.00425.x. PMID: 10954990

Therapy

Zhao Y, Gartner U, Smith FJ, McLean WH
J Invest Dermatol 2011 May;131(5):1045-52. Epub 2011 Mar 10 doi: 10.1038/jid.2011.41. PMID: 21390048
da Silva Santos PS, Mannarino F, Lellis RF, Osório LH
Dermatol Online J 2010 Oct 15;16(10):3. PMID: 21062597
Smith FJ, Hickerson RP, Sayers JM, Reeves RE, Contag CH, Leake D, Kaspar RL, McLean WH
J Invest Dermatol 2008 Jan;128(1):50-8. Epub 2007 Aug 30 doi: 10.1038/sj.jid.5701040. PMID: 17762855
Hannaford RS, Stapleton K
Australas J Dermatol 2000 Aug;41(3):175-7. doi: 10.1046/j.1440-0960.2000.00425.x. PMID: 10954990
Baden HP, Bronstein BR, Rand RE
J Am Acad Dermatol 1984 Sep;11(3):409-15. doi: 10.1016/s0190-9622(84)70182-4. PMID: 6237131

Prognosis

Samuelov L, Smith FJD, Hansen CD, Sprecher E
Br J Dermatol 2020 Mar;182(3):738-746. Epub 2020 Jan 14 doi: 10.1111/bjd.18794. PMID: 31823354
Forrest CE, Casey G, Mordaunt DA, Thompson EM, Gordon L
Pediatr Dermatol 2016 May;33(3):337-42. Epub 2016 Apr 4 doi: 10.1111/pde.12841. PMID: 27041546
Shah S, Boen M, Kenner-Bell B, Schwartz M, Rademaker A, Paller AS
JAMA Dermatol 2014 Feb;150(2):146-53. doi: 10.1001/jamadermatol.2013.6448. PMID: 24132595
Hickerson RP, Smith FJ, Reeves RE, Contag CH, Leake D, Leachman SA, Milstone LM, McLean WH, Kaspar RL
J Invest Dermatol 2008 Mar;128(3):594-605. Epub 2007 Oct 11 doi: 10.1038/sj.jid.5701060. PMID: 17914454
Feng YG, Xiao SX, Ren XR, Wang WQ, Liu A, Pan M
Br J Dermatol 2003 Mar;148(3):452-5. doi: 10.1046/j.1365-2133.2003.05152.x. PMID: 12653736

Clinical prediction guides

Knöbel M, O'Toole EA, Smith FJ
Cell Tissue Res 2015 Jun;360(3):583-9. Epub 2015 Jan 27 doi: 10.1007/s00441-014-2105-4. PMID: 25620412
Hickerson RP, Smith FJ, Reeves RE, Contag CH, Leake D, Leachman SA, Milstone LM, McLean WH, Kaspar RL
J Invest Dermatol 2008 Mar;128(3):594-605. Epub 2007 Oct 11 doi: 10.1038/sj.jid.5701060. PMID: 17914454
Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH, Lunny DP, Milstone LM, van Steensel MA, Munro CS, O'Toole EA, Celebi JT, Kansky A, Lane EB
J Investig Dermatol Symp Proc 2005 Oct;10(1):3-17. doi: 10.1111/j.1087-0024.2005.10202.x. PMID: 16250204
van Steensel MA, Koedam MI, Swinkels OQ, Rietveld F, Steijlen PM
Br J Dermatol 2001 Jul;145(1):157-61. doi: 10.1046/j.1365-2133.2001.04303.x. PMID: 11453928
King NM, Lee AM
J Craniofac Genet Dev Biol 1987;7(3):311-7. PMID: 3429608

Recent systematic reviews

Torchia D, Vega J, Schachner LA
Am J Clin Dermatol 2012 Feb 1;13(1):19-28. doi: 10.2165/11589050-000000000-00000. PMID: 21958358

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