2386 East Heritage Way, Suite B, Salt Lake City, Utah 84109 USA Phone +1-877-628-7300 • Email—Info@pachyonychia.org

www.pachyonychia.org

15 March 2005

Use of Articles in the Pachyonychia Congenita Bibliography

The articles in the PC Bibliography may be restricted by copyright laws. These have been made available to you by PC Project for the exclusive use in teaching, scholar-ship or research regarding Pachyonychia Congenita. To the best of our understanding, in supplying this material to you we have followed the guidelines of Sec 107 regarding fair use of copyright materials. That section reads as follows:

Sec. 107. - Limitations on exclusive rights: Fair use Notwithstanding the provisions of sections 106 and 106A, the fair use of a copyrighted work, including such use by reproduction in copies or phonorecords or by any other means specified by that section, for purposes such as criticism, comment, news reporting, teaching (including multiple copies for classroom use), scholarship, or research, is not an infringement of copyright. In determining whether the use made of a work in any particular case is a fair use the factors to be considered shall include - (1) the purpose and character of the use, including whether such use is of a commercial nature or is for nonprofit educational purposes; (2) the nature of the copyrighted work; (3) the amount and substantiality of the portion used in relation to the copyrighted work as a whole; and (4) the effect of the use upon the potential market for or value of the copyrighted work. The fact that a work is unpublished shall not itself bar a finding of fair use if such finding is made upon consideration of all the above factors.

We hope that making available the relevant information on Pachyonychia Congenita will be a means of furthering research to find effective therapies and a cure for PC.

Pachyonychia congenita with unusual dental findings: a case reportA. R. Pradeep, BDS, MDS,a and Chaitra Nagaraja, BDS,b Bangalore, IndiaDEPARTMENT OF PERIODONTICS, GOVERNMENT DENTAL COLLEGE AND HOSPITAL (Oral Surg OralMed Oral Pathol Oral Radiol Endod 2007;104:89-93)

Pachyonychia congenita is a rare genodermatosis, usu-ally inherited as an autosomal dominant trait, charac-terized by a variety of ectodermal abnormalities. Themost characteristic finding of affected patients is themarked subungual hyperkeratosis with thickening ofthe distal part of the nails. The other findings includepalmar and plantar keratosis, hyperhidrosis, follicularhyperkeratosis, and development of friction blisters.The oral findings in pachyonychia include leukokera-tosis of tongue, buccal mucosa, and palate, angularstomatitis, and presence of natal or neonatal teeth. Toour knowledge, this is the first report of pachyonychiacongenita associated with unusual dental findings, suchas presence of multiple localized idiopathic osteoscle-rosis, multiple retained primary roots, multiple taloncusps, and mesiodens.

Pachyonychia congenita (PC) is a rare form of he-reditary palmoplantar keratoderma. It was first docu-mented by Muller in 1904, but it was Jadassohn andLewandowsky in 19061 who reported palmoplantarkeratoderma and ectodermal defects. It is usually in-herited as an autosomal dominant trait with varyingdegree of penetrance, although autosomal recessiveforms have also been described.2

The manifestations in PC are chiefly subungual hy-perkeratosis with marked thickening of the distal por-tions of the nails and severe and disabling hyperkera-tosis of the palms and soles. Other possiblemanifestations include follicular hyperkeratosis ob-served on the face (e.g., temples, eyebrows) and on theextensor aspect of the proximal parts of the extremities,hyperhidrosis particularly on palms and soles, cornealchanges, and epidermal inclusion cysts.3-5

The oral findings in pachyonychia include leukok-eratosis of tongue or buccal mucosa, scalloped edges ofthe tongue, angular cheilitis, and dental abnormalities,including enamel hypoplasia, neonatal teeth, hypodon-

tia, and periodontitis and severe caries.6 Pachyonychiacongenita usually begins in infancy, but late-onset PC,referred to as pachyonychia tarda, which begins in thefourth or fifth decade, has been reported.7-8

CASE REPORTA 30-year-old female patient was referred from the Depart-

ment of Skin and Venereology, Victoria Hospital, Bangalore,India, to the Department of Periodontics, Government DentalCollege and Hospital, Bangalore, India, for treatment of poorperiodontal condition, with bleeding gums and halitosis. Themedical history of the patient revealed that she was diagnosedwith PC within 2 months of birth. Family history revealed thatthe maternal grandfather also suffered from the condition.

General physical examination showed hyperkeratotic fin-gernails and toenails (Figs. 1 and 2). Fingernails were af-fected more than the toenails. The affected nails showedthickening and hardening, subungual hyperkeratosis, and up-ward growth of the distal nail with hypercurvature. Patientgave a history of blisters on her feet after prolonged walking,especially during summers, blepharitis, and photosensitivityand exhibited classic symptoms of PC, which included hy-perhidrosis of palms and soles (Fig. 3) and hoarseness ofvoice.

In the preceding month, patient had developed few clustersof papules on her forearm and back. Based on the appearanceof pearly white papules with central indentation these werediagnosed as molluscum contagiosum (Fig. 4), and the diag-nosis was confirmed microscopically by the presence of mol-luscum bodies seen on hematoxylin and eosin staining.

Intraoral examination showed a striking feature of leukok-eratosis of the right dorsal and lateral aspect of the tongue(Fig. 5), right buccal mucosa, and angular cheilitis on theright side, and all the 6 maxillary anterior teeth showed taloncusps (Fig. 6). A mandibular left retained deciduous canineand buccally erupted left permanent canine was also seen. Onperiodontal examination, prominent local deposits and gen-eralized severely inflamed, erythematous, and enlarged gin-giva with bleeding on probing and an average probing depthof 5 mm were seen. However, because no clinical attachmentloss was observed, the pockets were considered as pseudo-pockets (Fig. 7). Periodontal indices were recorded: Plaqueindex9 score was 2.6, and modified gingival index10 scorewas 2.3.

Routine blood chemistry and biochemical investigations,which included random blood glucose, serum phosphorous,urea, and creatinine were carried out. All values were withinnormal limits except for a raised erythrocyte sedimentation

aProfessor and Head.bPost-graduate student.Received for publication Sep 5, 2005; returned for revision May 5,2006; accepted for publication May 17, 2006.1079-2104/$ - see front matter© 2007 Mosby, Inc. All rights reserved.doi:10.1016/j.tripleo.2006.05.011

89

rate of 87 mm/h (normal 15 mm/h in women, 6.5 mm/h inmen) which was possibly due to lower respiratory tract in-fection, for which she was under medication. To excludeonychomycosis, nail cultures were examined for the presenceof fungi and proved to be negative.

On routine radiologic examination, an interesting findingwas observed: elongated radiopacities were seen in the pos-terior regions in all quadrants of maxilla and mandible. Theradiopacities were surrounded by a thin radiolucent rim,which in turn was surrounded by a sclerotic lamina dura liketrabeculation, suggesting retained deciduous roots (Fig. 8) inthe mandible, but in the maxillary arch the radiopacity wasdensely homogeneous and did not show a perilesional radi-olucent rim, thus giving an impression of idiopathic osteo-sclerosis (Fig. 9).

An orthopantomograph revealed an unerupted mesiodens.A thorough scaling and root planing was carried out, and thepatient was put on maintenance therapy.

DISCUSSIONPachyonychia congenita is predominantly an autoso-

mal dominant group of ectodermal dysplasias charac-terized by hypertrophic nails and other ectodermalchanges that occur with the first months of life.

Four clinical subtypes of PC have been described sofar. PC-1, or Jadassohn-Lewandowsky type, named af-ter the professor of dermatology at the University ofBern in Switzerland Josef Jadassohn and his colleagueFelix Lewandowski, is associated with a heterozygousmissense mutation in the helix initiation motif of ker-atin (K) 16 gene and keratin 6 isoform (K6a). PC-2, orJackson-Lawler, type is associated with mutations inK17 and K6b.11

PC-1 (56% of cases) is associated with oral leukok-eratosis, palmoplantar keratoderma and follicular kera-tosis. PC-2 (25% of cases) has additional features suchas multiple pilosebaceous cysts, neonatal teeth, andpilitorti, and oral leukokeratosis occurs less frequently

Fig. 1. Fingernails showing subungual hyperkeratosis anddiscolouration. Patient has applied herbal coloring agent “me-hendi” to mask the color of the nail.

Fig. 2. Hyperkeratotic discolored nails of the feet.

Fig. 3. Hyperhidrosis of the palm.

Fig. 4. Molluscum contagiosum on the forearm. Multiplesmooth papules with central indentation.

OOOOE90 Pradeep and Nagaraja July 2007

in PC-2. Presence of widespread pilosebaceous cystsfollowing puberty is an important distinguishing factorin PC-2.

PC-3, or Shafer-Brunauer type (12% of cases), in-cludes features of both PC-1 and PC-2 with additionalfeatures of angular cheilitis, corneal dyskeratosis, andcataracts. PC-4 (7% of cases) has features of the other3 types with additional laryngeal involvement and men-tal retardation. The defective gene responsible for PC islocated on chromosome 17q and associated with muta-tions in K16 and K17.12

The familial nature of the disturbance was estab-lished in 1921, when Murray13 documented 7 affectedpersons in 3 generations of a family. In a similar report,Kumer and Loos in 193514 described 24 cases in a5-generation family. The phenotype was expanded, andthe autosomal dominant mode of inheritance was doc-umented in 1983 when Stieglitz and Centerwall15 pub-lished details of kindred with 17 affected individuals in4 generations.

Leukokeratosis of oral mucosa is a predominant fea-ture, mainly occurring on the tongue, buccal mucosa,and sometimes the gingiva. In some patients early toothdecay, periodontitis, and enamel hypoplasia may beevident. The oral leukokeratosis is not a precancerouslesion and can be differentiated from leukoplakia orother dysplastic lesions by performing oral biopsy orrecognizing its presence in patients with other expres-sions of PC.

Presently there is no cure for PC. Treatment is aimedat providing symptomatic relief for the patient, such assoaking feet and hands in saline or in 50% propyleneglycol solution followed by gentle debridement. Nailscan be managed by application of emollients or creamcontaining 10%-20% salicylic acid to soften the nailsprior to paring down the excess. Certain drugs havealso been used with no reports of long-term benefits,such as dilantin, fluorouracil, oral retinoids such asisotretinoin, etretinate, and keratolytic agents. In thepresent case, on routine radiologic examination multi-ple radiopacities were discovered in both jaws in thepremolar regions. Though a diagnosis of multiple lo-calized idiopathic osteosclerosis in the maxilla andmandible was made, a differential diagnosis of retainedroots of deciduous predecessors in the mandible, super-numerary teeth with aberrant morphology, complexcomposite odontomes, or hyperostotic areas was alsoconsidered.

Initially the radiopacities were thought to be aberrantsupernumerary teeth, but the radiopacities did not showany coronal component, which had a radiodensity ofenamel, and their shape did not suggest that a crownwas present. Also, there was no evidence of a follicle,follicular cyst, or dentigerous cyst associated with thesuperior aspect of the radiopacities.

Odontomes were also ruled out for the same reason,

Fig. 5. Leukokeratosis affecting the right dorsum of thetongue. Note depapillation on the affected site.

Fig. 6. Talon cusps seen on maxillary anterior teeth.

Fig. 7. Poor periodontal status of the patient at the time shereported to the dental clinic.

OOOOEVolume 104, Number 1 Pradeep and Nagaraja 91

because they did not exhibit radiodensity of enamel,and their shape was also not similar to a tooth as in thecase of compound composite odontomes. Althoughodontomes, which bear no structural resemblance to atooth, are classified as complex composite odontomes,such odontomes appear more globular in nature, withradiodensity similar to tooth structure and frequentlyassociated with an unerupted tooth.

Hyperostotic areas were excluded from the diagnosisbecause observation of radiographs under higher mag-nification showed that the radiodensity was homoge-neously devoid of trabeculation.

The presence of focal radiopaque area associatedwith the existing teeth, and the absence of fragments of

lamina dura surrounding the radiopacity led to thediagnosis of localized idiopathic osteosclerosis.

Idiopathic osteosclerosis is a focal deposition of bonewhich occurs even in the absence of trauma or anysystemic conditions. It is more common in the mandi-ble than in the maxilla. In the present case focal type ofidiopathic osteosclerosis was seen both in the maxillaand in the mandible. Generally, once the osteosclerosisdevelops, it does not show any regression and no treat-ment is required.

Although an interesting finding in this patient wasthe presence of radiopaque areas radiographically, this,in all likelihood, is not related to PC but rather is acoincidental finding.

Another interesting feature in the present case is thepresence of multiple talon cusps. The prevalence oftalon cusps is usually 1% to 8%. Its occurrence is mostcommon in the lateral incisors (55%) than central inci-sors (33%) and least on canines (6%). In the presentcase, talon cusps were seen on all 6 maxillary anteriorteeth, thereby being a very rare and interesting finding.

Thus this is a case report of a rare hereditary geno-dermatosis with very unusual dental findings which hadnot been previously reported.

REFERENCES1. Jadassohn J, Lewandowski F. Pachyonychia congenita. Keratosis

disseminata circumscripta (follicularis). Tylomata. Leukokerato-sis linguae. In: Neisser A, Jacobi E, editors. Ikonographia der-matologica, Vol. 1. Berlin: Urban and Schwarzenberg; 1906. p.29-1.

2. Haber RM, Rose TH. Autosomal recessive pachyonychia con-genita. Arch Dermatol 1986;122:919-23.

3. Schonfeld PH. The pachyonychia congenita syndrome. ActaDerm Venereol 1980;60:45-9.

Fig. 8. Orthopantomograph shows the presence of idiopathic osteosclerosis and an unerupted mesiodens.

Fig. 9. Intraoral periapical radiograph of maxillary right pos-terior quadrant showing idiopathic osteosclerosis between thepremolars.

OOOOE92 Pradeep and Nagaraja July 2007

4. Soderquist NA, Reed WB. Pachyonychia congenita with epider-mal cysts and other congenital dyskeratosis. Arch Dermatol1968;97:31-3.

5. Anneroth G. Pachyonychia congenita. Acta Derm Venereol1975;55:387-94.

6. Maldonado RR, Parish LC, Beare JM, editors. Textbook ofpediatric dermatology. Philadelphia: Saunders/Harcourt BraceJovanovich; 1989. p. 92.

7. Paller AS, Moore JA, Scher R. Pachyonychia congenita tarda. Alate onset form of pachyonychia congenita. Arch Dermatol 1991;127:701-3.

8. Hannaford RS, Stapleton K. Pachyonychia congenita tarda. Aus-tralas J Dermatol 2000;41:175-7.

9. Loe H. The gingival index, plaque index and the retention indexsystems. J Periodontol 1967;38:610-6.

10. Lobene RR, Weatherford T, Ross NM, Lamm RA, Menaker L. Amodified gingival index for use in clinical trial. Clin Prev Dent1986;8:3-6.

11. Drawber RPR, Baran R, de Berker D. Disorders of nails. In:Champion RH, Burton JL, Burns DA, Breathnach SM, editors.Rook/Wilkinson/Ebling textbook of dermatology. 6th ed. Ox-ford: Blackwell; 1998. p. 2834.

12. Munro CS, Carter S, Bryce S, Hall M, Rees JL, Kunkeler L, etal. A gene for pachyonychia congenita is closely linked to thekeratin gene cluster on 17q12-q21. J Med Genet 1994;31:675-8.

13. Murray FA. Congenital anomalies of the nails. 4 cases of hered-itary hypertrophy of the nail bed associated with a history oferupted teeth at birth. Br J Derm 1921;33:409-12.

14. Kumer L, Loos HO. Congenital pachyonychia (Riehl type). WienKlin Wochenschr 1935;48:174-8.

15. Stieglitz JB, Centerwall WR. Pachyonychia congenita (Jadas-sohn Lewandowsky syndrome). A 17 member, 4 generationpedigree with unusual respiratory and dental involvement. Am JMed Genet 1983;14:21-8.

Reprint requests:

Dr. A. R. PradeepDepartment of PeriodonticsGovernment Dental College#2, Fort RoadBangalore, Karnataka 560002Indiapradeep_gdc@sify.com

OOOOEVolume 104, Number 1 Pradeep and Nagaraja 93