Papillon-Lefevre syndrome: A report of two cases.

Papillon-Lefevre syndrome is a rare (1-4 cases per million) autosomal recessive disorder showing predominantly oral and dermatological manifestations in the form of aggressive periodontitis affecting both primary and permanent dentition and palmoplantar hyperkeratosis. Genetic studies have shown that mutations in the major gene locus of chromosome 11q14 with loss of function of cathepsin C gene are responsible for Papillon-Lefevre syndrome. This report presents two siblings with classic signs and symptoms of Papillon-Lefevre syndrome. The exact cause for periodontal destruction in patients with Papillon-Lefevre syndrome is not known but it is thought to be due to defect in neutrophil function, immune suppression and mutations in cathepsin C gene.

INTRODUCTION

Papillon-Lefevre syndrome belongs to a heterogeneous group of skin diseases that are characterized by hyperkeratosis of palms and soles. Papillon-Lefevre syndrome is inherited as an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early loss of primary and permanent teeth. Nineteen different types of palmoplantar keratoderma have been identified. Papillon-Lefevre syndrome differs from other types of palmoplantar keratoderma in its severe periodontopathy and premature loss of primary and permanent dentition.[1]

Papillon-Lefevre syndrome was first described in 1924 by Papillon M M and Lefevre P in two siblings. It is inherited as an autosomal recessive disorder. Fifty percent of the patients with Papillon-Lefevre syndrome appear to have been derived from consanguineous marriages.[2]

Hart et al., showed that mutations of cathepsin C gene are responsible for Papillon-Lefevre syndrome and a region of chromosomes (11q14-21) is responsible for this.[3]

CASE REPORT

An 18-year-old boy reported to the department of Periodontology and Implant Dentistry, Bharati Vidyapeeth University Dental College and Hospital, Navi-Mumbai for the treatment of generalized mobility of teeth and bleeding gums.

Family history was important and contributory. There was a history of consanguineous marriage of the parents. Both parents were healthy. History reveled that his 16-year-old brother also complained of similar problems.

Systemic history-both the cases showed marked palmoplantar hyperkeratosis. Both patients were alert and cooperative. Onset of skin disorder was by the age of 2-3 years. Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows.

Clinical and radiographical features

Case 1

Patient showed bilateral hyperkeratosis of palms, soles, dorsal surface of fingers and knees [Figures 1 and 2]. Intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade II mobility. Orthopantomograph showed severe horizontal bone loss. [Figures 3–5].

Figure 1

Hyperkeratosis of palms and soles - case 1

Figure 2

Hyperkeratosis of knees - case 1

Figure 3

Intra-oral view-maxilla - case 1

Figure 5

OPG - case 1

Intra-oral view-mandible - case 1

Case 2

This patient too showed considerable hyperkeratosis of palms and soles [Figure 6]. Intraoral examination showed more teeth present. Orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds [Figures 7–9]. All teeth had deep periodontal pockets and grade II mobility.

Figure 6

Hyperkeratosis of palms and soles - case 2

Figure 7

Intra-oral view-maxilla - case 2

Figure 9

OPG - case 2

Intra-oral view-mandible - case 2

Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits.

On the basis of history, clinical and radiographical features a diagnosis of Papillon-Lefevre syndrome was made.

Treatment

A multidisciplinary approach is essential for the treatment of the condition. Attempt to treat skin lesions was made retinoid administration under physician's supervision. Thorough scaling and root planing of all teeth was carried out along with administration of systemic antibiotics. Hopeless teeth were extracted and partial dentures were planned.[4]

DISCUSSION

Papillon-Lefevre syndrome is an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressive periodontitis. Papillon-Lefevre syndrome usually appears in childhood. Males and females are equally affected. Patients are normal at birth. Skin lesions develop concurrently with oral lesions and may extend to dorsal surfaces of hands and feet. Another form of disease associated with palmoplantar keratosis and severe aggressive periodontitis has been named Haim-Munk syndrome. It differs from Papillon-Lefevre syndrome in symptoms such as arachnodactyly, acroosterolysis and onychogryphosis.[5]

In Papillon-Lefevre syndrome there is severe periodontopathy and premature loss of primary and permanent dentition. Teeth are lost in eventually the same sequence in which they are erupted. When the last tooth is lost gingiva acquires a normal appearance. The permanent dentition starts to erupt at proper time, but around 8-9 years of age periodontal destruction is repeated in the same manner as in primary dentition. All permanent teeth are usually lost before 14-16 years of age.

Pathophisiology

In subjects with Papillon-Lefevre syndrome there is defective cathepsin C production. The gene for cathepsin C lies on chromosome 11. Cathepsin C is a lysosomal protease and it is distributed to many tissues.[6] Cathepsin C is involved in the activation of T cells. The exact biochemical defect leading to periodontal disease is still unclear. In 1942, Wannenmacher suggested that Papillon-Lefevre syndrome was due to a combination of ecto and mesodermal malformations. Saahan S et al. suggested that a functional imbalance of collagenolytic activity in the periodontal ligament was responsible for periodontitis in Papillon-Lefevre syndrome. In 1984, VanDyke suggested that neutrophils from an individual with Papillon-Lefevre syndrome exhibit decreased receptor affinity for chemotaxins such as formyl peptides. Page RC et al. in suggested defective cementum formation to be the cause for periodontitis in Papillon-Lefevre syndrome.[7] Papillon-Lefevre syndrome is associated with myeloperoxide deficiency, low integrin expression, defective phagocytosis and chemotaxis. Neutrophils from individuals with Papillon-Lefevre syndrome exhibit decreased affinity for chemotaxins.[28]

Hattab et al., reported four cases of Papillon-Lefevre syndrome affecting two Jordanian families with eight children. In all patients there was a relationship between increased severity of skin lesions and seasonal variations and intensified periodontal destruction.[1] Lass et al. in three multiplex families, one Ethiopian and two German, demonstrated linkage of Papillon-Lefevre syndrome with chromosome 11q13-q14.[9] Fischer et al., conducted a primary genome wide search by homozygosity mapping in a large consanguineous family with four affected siblings. Homozygosity and linkage was demonstrated in region 11q14 of chromosome. Toomes et al., showed that in patients with Papillon-Lefevre syndrome gene for cathepsin C which lies in chromosome 11 had undergone mutation resulting in decreased cathepsin C production.[6]

Hart et al., reported mutations in cathepsin C gene in patients with Papillon-Lefevre syndrome from five different countries.[3]

In conclusion, we have reported two cases of Papillon-Lefevre syndrome. Further studies in the field of microbiology and genetics are necessary to find the exact cause of periodontal destruction in such patients, so that best possible dental treatment can be rendered to them.