Papillon–Lefevre syndrome: Reporting consanguinity as a risk factor
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12 CASE REPORT
6 Aasim Farooq Shaha,*Q1 , Pradeep Tangade
a,1, Swatantra Agarwal b,2
7a Department of Public Health Dent
8 Uttar Pradesh, India9
b Department of Prosthodontics, Kot
10 R vised11
15 PapillonLefevre syndrome;16 Consanguinity;17
ized by palmoplantar hyperkeratosis associated with severe early-onset periodontitis and premature
loss of primary and permanent teeth. This report describes two cases of PLS in 28-year-old female
thickening, aking, and scaling of the skin on the palms and soles of the feet. On oral examination,
2014 Production and hosting by Elsevier B.V. on behalf of King Saud University.19
20 1. Introduction
25gene (CTSC) on chromosome 11q14. Most patients with this26mutations (Hart27disorder can be28ther synd29ty has bee302008; Zha31
33et al., 2012; Varsha and Nilesh, 2010). Consanguineous mar-34riage is a cultural practice with ancient roots, and 20% of35the worlds population currently lives in communities that pre-36fer this form of marriage (Modell and Darr, 2002). Q5Arab coun-37tries have the highest rates (2050%) of consanguineous38marriage in the world (Vardi-Saliternik et al., 2002).39Q6In 1924, the French physicians Papillon and Lefevre40described a condition characterized by palmoplantar41hyperkeratosis, severe early-onset periodontitis, and premature
E-mail addresses: firstname.lastname@example.org (A.F. Shah), ptanga
email@example.com (P. Tangade), firstname.lastname@example.org
(S. Agarwal).1 Mobile: +91 9997466339; fax: +91 0591 2452996.2 Mobile: +91 9837043736.
Peer review under responsibility of King Saud University.
Production and hosting by Elsevier
The Saudi Dental Journal (2014) xxx, xxxxxx
The Saudi De
SDENTJ 159 No. of Pages 6
23 April 2014Lundgren, 2001). Several previous reports have described PLSin the children of consanguineously married parents (Khan* Corresponding author. Mobile: +91 9456910498.PapillonLefevre syndrome (PLS) is a type IV palmoplantar
keratosis (Papillon and Lefevre, 1924; Stevens et al., 1996).The etiology of PLS appears to be genetic in most cases, char-acterized by mutations affecting both alleles of the cathepsin C
syndrome are homozygous for these CTSCet al., 1999, 2000; Toomes et al., 1999). The
hereditary, acquired, or associated with oPLS is autosomal recessive, and consanguinionstrated in 2040% of patients (Kaya et al.,1013-9052 2014 Production and hosting by Elsevier B.V. on behalf of King Saud University.http://dx.doi.org/10.1016/j.sdentj.2014.02.004
Please cite this article in press as: Shah, A.F. et al., PapillonLefevre syndrome: Reporting consanguinity as a risk factor. The Saudi Dentnal (2014), http://dx.doi.org/10.1016/j.sdentj.2014.02.004romes.n dem-ng andthe female patient presented completely resorbed maxillary and mandibular alveolar ridges with
retention of only the third molars. The male patient retained only teeth 18, 13, 28, 38, and 45. Based
on complete histories and clinical examination ndings, a nal diagnosis of PLS was made and
treatment was initiated using an interdisciplinary dental approach in both cases.Periodontitis;
Premature tooth loss
and 16-year-old male siblings with consanguineously married parents. The patients presented to the
Department of Public Health Dentistry of a dental education and research institute in India witheceived 17 October 2013; re
KEYWORDS Aistry, Kothiwal Dental College & Research Centre, Kanth Road, Moradabad 244001,
hiwal Dental College & Research Centre, Kanth Road, Moradabad 244001, Uttar Pradesh, India
31 December 2013; accepted 11 February 2014
bstract PapillonLefevre syndrome (PLS) is an autosomal recessive genetic disorder character-PapillonLefevre syndrome: Rconsanguinity as a risk factorporting
42 loss of primary and permanent teeth in a brother and sister43 (Ashri, 2008; Hattab and Amin, 2005). Frequent pyogenic skin44 infection, nail dystrophy, and hyperhidrosis are also com-45 monly associated with PLS (Bergman et al., 1988). Patients46 with PLS also typically show the underlying disease associated47 with functional or quantitative neutrophil abnormalities, and48 50% of patients are immunocompromised (Van-Dyke et al.,49 1984). PLS affects both sexes equally. The estimated preva-50 lence of this syndrome is 14 per million in the general popu-51 lation, and its carrier rate is 24 per 1000 (Angel et al., 2002)Q7 .52 Several other disorders, such as Feers syndrome, palmoplan-53 tar ectodermal dysplasia, and HaimMunk syndrome, have54 similar clinical features (Ashri, 2008; Singla et al., 2010).
55Q8The present report describes two classical cases of PLS in a5628-year-old woman and a 16-year-old boy with consanguine-57ously married parents.
582. Case reports
592.1. Case 1
60A 28-year-old woman (Fig. 1c) presented to the Department of61Public Health Dentistry, Kothiwal Dental College and62Research Centre, Moradabad, Uttar Pradesh, India, with the63chief complaint of premature loss of permanent dentition.
2 A.F. Shah et al.
SDENTJ 159 No. of Pages 6
23 April 2014Figure 1 Colour slides of Case 1 (a & b) showing thickening, ak
over the skin (c) presenting the facial prole (d) intraoral photogra
alveolar ridges with normal overlying mucosa.Please cite this article in press as: Shah, A.F. et al., PapillonLefevre syndrnal (2014), http://dx.doi.org/10.1016/j.sdentj.2014.02.004, scaling, psoriasiform, erythematous, yellowish, keratotic plaques
revealing all third molars are present also the partially edentulousome: Reporting consanguinity as a risk factor. The Saudi Dental Jour-
64 She was the rst child of healthy consanguineously married65 parents. Collection of a detailed family history revealed that66 the patients grandparents were also consanguineously married67 and that her siblings exhibited similar clinical signs. The68 patients dental history indicated that her deciduous teeth69 had erupted normally, but had exfoliated gradually by the70 age of 34 years.Q9 Her permanent teeth were also lost prema-71 turely, soon after normal eruption. The patient also reported72 cycles of skin lesion exacerbation and remission and multiple73 infections since early childhood, resulting in regular visits to74 dermatologists.75 General examination showed persistent thickening, ak-76 ing, and scaling of the skin of the patients palms and soles77 of the feet (Fig. 1a and b), associated with swollen and fri-78 able gingiva since the age of 4 years.Q10 Symmetrical, well-79 demarcated, psoriasiform, erythematous, yellowish keratotic80 plaques covered the soles of her feet and extended onto the81 dorsal surfaces (Fig. 1a and b). Dystrophy and transverse82 grooving of the nails, more pronounced on the toenails83 than on the ngernails, was also present. The skin of the84 patients left and right palms, elbows, and knees was exfo-85 liating, and the underlying skin appeared red and shiny,86
104not extracted to aid denture retention; the patient was advised105to visit the clinic every 3 months for monitoring of these teeth Q14.
1062.2. Case 2
107A 16-year-old male patient (Fig. 3c) presented to the Depart-108ment of Public Health Dentistry of the Kothiwal Dental Col-109lege and Research Centre complaining of esthetic problems110and difculty eating for 1 year due to the loss of permanent111teeth. He was the brother of the patient described in case 1,112the second child of healthy consanguineously married parents.113The patient had a history of skin thickening and scaling on the114palms and soles of the feet since early childhood. His past med-115ical and dental history revealed frequent upper respiratory116infection, early exfoliation of the deciduous dentition, and loss117of all permanent teeth Q15by the age of 14 years due to excessive118mobility.119Physical examination revealed well-demarcated, yellow ker-120atotic plaques on the bilateral palms and soles of the feet121(Fig. 3a and b), extending onto the dorsal surfaces of the hands122and feet. The patients knees and elbows were also affected,123but to a lesser degree than the palmoplantar surfaces.124
PapillonLefevre syndrome 3
SDENTJ 159 No. of Pages 6
23 April 2014suggestive of keratoderma.Intraoral examination revealed retention of only the four
third molars and complete resorption of the edentulous por-tion of the mandibular ridge, with normal mucosa (Fig. 1d).
None of the third molars showed mobility or was associatedwith gingival inammation. An orthopantomograph con-rmed alveolar resorption and the presence of only the third
molars (Fig. 2).Laboratory investigations, such as a complete blood count,
blood chemistry prole, and liver function tests, produced
results within normal limits. Immunological studies revealedlow CD3+ and CD4+ counts. Based on the patients historyand clinical ndings, PLS was diagnosed and consanguinity
was proposed as a high-risk factor.After explaining all possible treatment modalities to the
patient, a treatment plan was initiated. Considering her soci-odemographic and economic prole, treatment included the
fabrication of full dentures. The maxillary third molars were
Figure 2 Radiograph (Orthopantomograph) of Case 1 showPlease cite this article in press as: Shah, A.F. et al., PapillonLefevre syndrnal (2014), http://dx.doi.org/10.1016/j.sdentj.2014.02.004Intraoral examination showed that teeth 18, 13, 28, 38, and
45 were present (Fig. 3d). The gingiva surrounding these teethappeared normal, except for that around tooth 45, whichexhibited grade I mobility. No other tooth showed mobilityor was associated with gingival inammation. Edentulous por-
tions of the alveolar ridges were completely resorbed.Hematological examination revealed a hemoglobin concen-
tration of 10.0 g/dl, total leukocyte count of 9200, and erythro-
cyte sedimentation rate of 20 mm/h. Biochemical ndings werewithin normal limits. Based on patients history and clinicaland laboratory ndings, PLS was diagnosed and consanguin-
ity was considered to be a high-risk factor.Considering patients sociodemographic prole, treatment
included the extraction of tooth 45 and fabrication of dentures
for resorbed alveolar areas. Teeth 18, 13, and 38, which werestable, were retained to aid denture retention. The patientwas advised to visit the clinic at 3-month intervals for theassessment of tooth stability.
edentulous alveolar ridges with presence of all third molars.ome: Reporting consanguinity as a risk factor. The Saudi Dental Jour-
4 A.F. Shah et al.
SDENTJ 159 No. of Pages 6
23 April 20143. Discussion
PLS is a rare disorder with autosomal recessive inheritance,meaning that both parents of affected individuals are pheno-
typically healthy and a family history of the disease is lacking,except often in siblings. Both parents must carry the autosomalgene for the syndrome to appear in their offspring, and the
chance of producing offspring with PLS is 25% (Ashri, 2008;Hattab and Amin, 2005).
Several authors have documented cases of PLS character-ized by late-onset periodontitis and early-onset palmoplantar
hyperkeratosis or, more generally, skin manifestations
Figure 3 Colour slides of Case 2 (a & b) showing well-demarcated,
prole of case 2 while (d) presents intraoral picture revealing presence
canine and lower right premolar with receded as well as inamed ging
also be seen.
Please cite this article in press as: Shah, A.F. et al., PapillonLefevre syndrnal (2014), http://dx.doi.org/10.1016/j.sdentj.2014.02.004153(Brown et al., 1993; Bullon et al., 1993; Q21Willett et al., 1985).154Numerous authors have also reported cases of PLS with clin-155ical features similar to those described in the present report156(Almuneef et al., 2003; Khan et al., 2012; Papillon and157Lefevre, 1924; Varsha and Nilesh, 2010) and/or occurring in158siblings (Angel et al., 2002; Bullon et al., 1993; Hattab and159Amin, 2005; Sharma et al., 2013; Ullbro et al., 2003).160Three main factors have been proposed to underlie the ini-161tiation and progression of PLS: (1) impairment of neutrophil162chemotaxis, phagocytosis, and bactericidal activities with163decreased cell migration (Liu et al., 2000; Lundgren et al.,1642005); (2) the presence of virulent Gram-negative anaerobic
yellow keratotic plaque on palms and soles (c) presents the facial
of both maxillary and one mandibular third molars, upper right
iva, edentulous alveolar ridges with normal overlying mucosa can
ome: Reporting consanguinity as a risk factor. The Saudi Dental Jour-
165 pathogens (Actinobacillus actinomycetemcomitans) in peri-166
224informed written consent was acquired from both the patients225
280syndrome. J. Clin. Periodontol. 23, 176179.281Lundgren, T., Parhar, R.S., et al, 2005. Impaired cytotoxicity in282
PapillonLefevre syndrome 5
SDENTJ 159 No. of Pages 6
23 April 2014odontal plaque and pockets (Bergman et al., 1988; Gonzalezet al., 1997); and (3) a defect of immune-mediated mechanisms
involving reduced lymphocyte response to pathogens,decreased helper/suppressor T-cell ratio, poor monocytic func-tion, elevated serum immunoglobulin G level, and degenera-
tive changes in plasma cells (Pilger et al., 2003). The CTSCgene responsible for PLS is located on chromosome 11q14-21, where it encodes a lysosomal protease in the interval
between D11S4082 and D11S931.Patients with PLS always exfoliate deciduous teeth prema-
turely, after which gingival inammation subsides and the gin-giva appears healthy. However, gingivitis and periodontitis
recur with the eruption of permanent teeth, often leading topremature exfoliation of all teeth except the third molars. Mer-cury intoxication (Feers syndrome) may also cause premature
loss of deciduous and/or permanent teeth, but it can be distin-guished from PLS because it is characterized by red desquama-tion, often involving both extremities, erythrocyanosis, muscle
pain, insomnia, sweating, tachycardia, and psychic distur-bances (Singla et al., 2010). PLS can also be differentiated fromother syndromes causing palmoplantar hyperkeratosis, such as
HowelEvans, Greithers, and Vohwinkel syndromes, as noneof these conditions presents with periodontitis (Kaur, 2013).
In patients with PLS, routine blood investigations and liverfunction tests usually yield values within normative ranges.
Neutrophil counts, lymphocyte counts, and/or monocyticfunction are decreased in some p...