Use of Articles in the Pachyonychia Congenita Bibliography
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1 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, scholarship 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 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 The fact that a work is unpublished shall not itself bar a finding of fair use if such finding is made upon consideration of all the above factors.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 East Heritage Way, Suite B, Salt Lake City, Utah USA Phone Info@pachyonychia.org
2 Pachyonychia congenita with unusual dental findings: a case report A. R. Pradeep, BDS, MDS, a and Chaitra Nagaraja, BDS, b Bangalore, India DEPARTMENT OF PERIODONTICS, GOVERNMENT DENTAL COLLEGE AND HOSPITAL (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:89-93) a Professor and Head. b Post-graduate student. Received for publication Sep 5, 2005; returned for revision May 5, 2006; accepted for publication May 17, /$ - see front matter 2007 Mosby, Inc. All rights reserved. doi: /j.tripleo Pachyonychia congenita is a rare genodermatosis, usually inherited as an autosomal dominant trait, characterized by a variety of ectodermal abnormalities. The most characteristic finding of affected patients is the marked subungual hyperkeratosis with thickening of the distal part of the nails. The other findings include palmar and plantar keratosis, hyperhidrosis, follicular hyperkeratosis, and development of friction blisters. The oral findings in pachyonychia include leukokeratosis of tongue, buccal mucosa, and palate, angular stomatitis, and presence of natal or neonatal teeth. To our knowledge, this is the first report of pachyonychia congenita associated with unusual dental findings, such as presence of multiple localized idiopathic osteosclerosis, multiple retained primary roots, multiple talon cusps, and mesiodens. Pachyonychia congenita (PC) is a rare form of hereditary palmoplantar keratoderma. It was first documented by Muller in 1904, but it was Jadassohn and Lewandowsky in who reported palmoplantar keratoderma and ectodermal defects. It is usually inherited as an autosomal dominant trait with varying degree of penetrance, although autosomal recessive forms have also been described. 2 The manifestations in PC are chiefly subungual hyperkeratosis with marked thickening of the distal portions of the nails and severe and disabling hyperkeratosis of the palms and soles. Other possible manifestations include follicular hyperkeratosis observed on the face (e.g., temples, eyebrows) and on the extensor aspect of the proximal parts of the extremities, hyperhidrosis particularly on palms and soles, corneal changes, and epidermal inclusion cysts. 3-5 The oral findings in pachyonychia include leukokeratosis of tongue or buccal mucosa, scalloped edges of the tongue, angular cheilitis, and dental abnormalities, including enamel hypoplasia, neonatal teeth, hypodontia, and periodontitis and severe caries. 6 Pachyonychia congenita usually begins in infancy, but late-onset PC, referred to as pachyonychia tarda, which begins in the fourth or fifth decade, has been reported. 7-8 CASE REPORT A 30-year-old female patient was referred from the Department of Skin and Venereology, Victoria Hospital, Bangalore, India, to the Department of Periodontics, Government Dental College and Hospital, Bangalore, India, for treatment of poor periodontal condition, with bleeding gums and halitosis. The medical history of the patient revealed that she was diagnosed with PC within 2 months of birth. Family history revealed that the maternal grandfather also suffered from the condition. General physical examination showed hyperkeratotic fingernails and toenails (Figs. 1 and 2). Fingernails were affected more than the toenails. The affected nails showed thickening and hardening, subungual hyperkeratosis, and upward growth of the distal nail with hypercurvature. Patient gave a history of blisters on her feet after prolonged walking, especially during summers, blepharitis, and photosensitivity and exhibited classic symptoms of PC, which included hyperhidrosis of palms and soles (Fig. 3) and hoarseness of voice. In the preceding month, patient had developed few clusters of papules on her forearm and back. Based on the appearance of pearly white papules with central indentation these were diagnosed as molluscum contagiosum (Fig. 4), and the diagnosis was confirmed microscopically by the presence of molluscum bodies seen on hematoxylin and eosin staining. Intraoral examination showed a striking feature of leukokeratosis of the right dorsal and lateral aspect of the tongue (Fig. 5), right buccal mucosa, and angular cheilitis on the right side, and all the 6 maxillary anterior teeth showed talon cusps (Fig. 6). A mandibular left retained deciduous canine and buccally erupted left permanent canine was also seen. On periodontal examination, prominent local deposits and generalized severely inflamed, erythematous, and enlarged gingiva with bleeding on probing and an average probing depth of 5 mm were seen. However, because no clinical attachment loss was observed, the pockets were considered as pseudopockets (Fig. 7). Periodontal indices were recorded: Plaque index 9 score was 2.6, and modified gingival index 10 score was 2.3. Routine blood chemistry and biochemical investigations, which included random blood glucose, serum phosphorous, urea, and creatinine were carried out. All values were within normal limits except for a raised erythrocyte sedimentation 89
3 90 Pradeep and Nagaraja July 2007 Fig. 1. Fingernails showing subungual hyperkeratosis and discolouration. Patient has applied herbal coloring agent mehendi to mask the color of the nail. Fig. 3. Hyperhidrosis of the palm. Fig. 4. Molluscum contagiosum on the forearm. Multiple smooth papules with central indentation. Fig. 2. Hyperkeratotic discolored nails of the feet. rate of 87 mm/h (normal 15 mm/h in women, 6.5 mm/h in men) which was possibly due to lower respiratory tract infection, for which she was under medication. To exclude onychomycosis, nail cultures were examined for the presence of fungi and proved to be negative. On routine radiologic examination, an interesting finding was observed: elongated radiopacities were seen in the posterior regions in all quadrants of maxilla and mandible. The radiopacities were surrounded by a thin radiolucent rim, which in turn was surrounded by a sclerotic lamina dura like trabeculation, suggesting retained deciduous roots (Fig. 8) in the mandible, but in the maxillary arch the radiopacity was densely homogeneous and did not show a perilesional radiolucent rim, thus giving an impression of idiopathic osteosclerosis (Fig. 9). An orthopantomograph revealed an unerupted mesiodens. A thorough scaling and root planing was carried out, and the patient was put on maintenance therapy. DISCUSSION Pachyonychia congenita is predominantly an autosomal dominant group of ectodermal dysplasias characterized by hypertrophic nails and other ectodermal changes that occur with the first months of life. Four clinical subtypes of PC have been described so far. PC-1, or Jadassohn-Lewandowsky type, named after the professor of dermatology at the University of Bern in Switzerland Josef Jadassohn and his colleague Felix Lewandowski, is associated with a heterozygous missense mutation in the helix initiation motif of keratin (K) 16 gene and keratin 6 isoform (K6a). PC-2, or Jackson-Lawler, type is associated with mutations in K17 and K6b. 11 PC-1 (56% of cases) is associated with oral leukokeratosis, palmoplantar keratoderma and follicular keratosis. PC-2 (25% of cases) has additional features such as multiple pilosebaceous cysts, neonatal teeth, and pilitorti, and oral leukokeratosis occurs less frequently
4 Volume 104, Number 1 Pradeep and Nagaraja 91 Fig. 5. Leukokeratosis affecting the right dorsum of the tongue. Note depapillation on the affected site. Fig. 7. Poor periodontal status of the patient at the time she reported to the dental clinic. Fig. 6. Talon cusps seen on maxillary anterior teeth. in PC-2. Presence of widespread pilosebaceous cysts following puberty is an important distinguishing factor in PC-2. PC-3, or Shafer-Brunauer type (12% of cases), includes features of both PC-1 and PC-2 with additional features of angular cheilitis, corneal dyskeratosis, and cataracts. PC-4 (7% of cases) has features of the other 3 types with additional laryngeal involvement and mental retardation. The defective gene responsible for PC is located on chromosome 17q and associated with mutations in K16 and K The familial nature of the disturbance was established in 1921, when Murray 13 documented 7 affected persons in 3 generations of a family. In a similar report, Kumer and Loos in described 24 cases in a 5-generation family. The phenotype was expanded, and the autosomal dominant mode of inheritance was documented in 1983 when Stieglitz and Centerwall 15 published details of kindred with 17 affected individuals in 4 generations. Leukokeratosis of oral mucosa is a predominant feature, mainly occurring on the tongue, buccal mucosa, and sometimes the gingiva. In some patients early tooth decay, periodontitis, and enamel hypoplasia may be evident. The oral leukokeratosis is not a precancerous lesion and can be differentiated from leukoplakia or other dysplastic lesions by performing oral biopsy or recognizing its presence in patients with other expressions of PC. Presently there is no cure for PC. Treatment is aimed at providing symptomatic relief for the patient, such as soaking feet and hands in saline or in 50% propylene glycol solution followed by gentle debridement. Nails can be managed by application of emollients or cream containing 10%-20% salicylic acid to soften the nails prior to paring down the excess. Certain drugs have also been used with no reports of long-term benefits, such as dilantin, fluorouracil, oral retinoids such as isotretinoin, etretinate, and keratolytic agents. In the present case, on routine radiologic examination multiple radiopacities were discovered in both jaws in the premolar regions. Though a diagnosis of multiple localized idiopathic osteosclerosis in the maxilla and mandible was made, a differential diagnosis of retained roots of deciduous predecessors in the mandible, supernumerary teeth with aberrant morphology, complex composite odontomes, or hyperostotic areas was also considered. Initially the radiopacities were thought to be aberrant supernumerary teeth, but the radiopacities did not show any coronal component, which had a radiodensity of enamel, and their shape did not suggest that a crown was present. Also, there was no evidence of a follicle, follicular cyst, or dentigerous cyst associated with the superior aspect of the radiopacities. Odontomes were also ruled out for the same reason,
5 92 Pradeep and Nagaraja July 2007 Fig. 8. Orthopantomograph shows the presence of idiopathic osteosclerosis and an unerupted mesiodens. Fig. 9. Intraoral periapical radiograph of maxillary right posterior quadrant showing idiopathic osteosclerosis between the premolars. because they did not exhibit radiodensity of enamel, and their shape was also not similar to a tooth as in the case of compound composite odontomes. Although odontomes, which bear no structural resemblance to a tooth, are classified as complex composite odontomes, such odontomes appear more globular in nature, with radiodensity similar to tooth structure and frequently associated with an unerupted tooth. Hyperostotic areas were excluded from the diagnosis because observation of radiographs under higher magnification showed that the radiodensity was homogeneously devoid of trabeculation. The presence of focal radiopaque area associated with the existing teeth, and the absence of fragments of lamina dura surrounding the radiopacity led to the diagnosis of localized idiopathic osteosclerosis. Idiopathic osteosclerosis is a focal deposition of bone which occurs even in the absence of trauma or any systemic conditions. It is more common in the mandible than in the maxilla. In the present case focal type of idiopathic osteosclerosis was seen both in the maxilla and in the mandible. Generally, once the osteosclerosis develops, it does not show any regression and no treatment is required. Although an interesting finding in this patient was the presence of radiopaque areas radiographically, this, in all likelihood, is not related to PC but rather is a coincidental finding. Another interesting feature in the present case is the presence of multiple talon cusps. The prevalence of talon cusps is usually 1% to 8%. Its occurrence is most common in the lateral incisors (55%) than central incisors (33%) and least on canines (6%). In the present case, talon cusps were seen on all 6 maxillary anterior teeth, thereby being a very rare and interesting finding. Thus this is a case report of a rare hereditary genodermatosis with very unusual dental findings which had not been previously reported. REFERENCES 1. Jadassohn J, Lewandowski F. Pachyonychia congenita. Keratosis disseminata circumscripta (follicularis). Tylomata. Leukokeratosis linguae. In: Neisser A, Jacobi E, editors. Ikonographia dermatologica, Vol. 1. Berlin: Urban and Schwarzenberg; p Haber RM, Rose TH. Autosomal recessive pachyonychia congenita. Arch Dermatol 1986;122: Schonfeld PH. The pachyonychia congenita syndrome. Acta Derm Venereol 1980;60:45-9.
6 Volume 104, Number 1 Pradeep and Nagaraja Soderquist NA, Reed WB. Pachyonychia congenita with epidermal cysts and other congenital dyskeratosis. Arch Dermatol 1968;97: Anneroth G. Pachyonychia congenita. Acta Derm Venereol 1975;55: Maldonado RR, Parish LC, Beare JM, editors. Textbook of pediatric dermatology. Philadelphia: Saunders/Harcourt Brace Jovanovich; p Paller AS, Moore JA, Scher R. Pachyonychia congenita tarda. A late onset form of pachyonychia congenita. Arch Dermatol 1991; 127: Hannaford RS, Stapleton K. Pachyonychia congenita tarda. Australas J Dermatol 2000;41: Loe H. The gingival index, plaque index and the retention index systems. J Periodontol 1967;38: Lobene RR, Weatherford T, Ross NM, Lamm RA, Menaker L. A modified gingival index for use in clinical trial. Clin Prev Dent 1986;8: 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. Oxford: Blackwell; p 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: Murray FA. Congenital anomalies of the nails. 4 cases of hereditary hypertrophy of the nail bed associated with a history of erupted teeth at birth. Br J Derm 1921;33: Kumer L, Loos HO. Congenital pachyonychia (Riehl type). Wien Klin Wochenschr 1935;48: Stieglitz JB, Centerwall WR. Pachyonychia congenita (Jadassohn Lewandowsky syndrome). A 17 member, 4 generation pedigree with unusual respiratory and dental involvement. Am J Med Genet 1983;14:21-8. Reprint requests: Dr. A. R. Pradeep Department of Periodontics Government Dental College #2, Fort Road Bangalore, Karnataka India pradeep_gdc@sify.com
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