Kindler syndrome and periodontal disease: review of the literature and a 12-year follow-up case

Abstract

Background: The association of aggressive periodontitis with Kindler syndrome was based on a single case in 1996 and later confirmed with a larger population. Since then, significant research has greatly increased our understanding of the molecular pathology of this disorder. We review recent advances in the molecular mechanisms of the syndrome and present a maintenance case report of a patient who has been followed in our clinic.

Methods: A female patient who was diagnosed with Kindler syndrome and aggressive periodontitis at the age of 16 years has been followed and treated in our clinic for 12 years. Her main treatment has been maintenance therapy following her initial treatment and restorative work previously documented. Gingival biopsies obtained during the recent extraction of hopeless maxillary molars were used for histologic assessment of gingival tissue attachment apparatus and to isolate gingival fibroblasts. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using these cells to confirm the lack of expression of kindlin-1.

Results: RT-PCR showed the total loss of kindlin-1 mRNA in cultured gingival fibroblasts, supporting the clinical diagnosis of Kindler syndrome. Tissue biopsies revealed atypical pocket epithelium. Maintenance therapy has been moderately successful. Teeth that were recently lost had a poor prognosis at the initial assessment. The patient's gingiva and oral mucosa continue to be fragile with episodes of sloughing and inflammation.

Conclusions: Periodontitis in Kindler syndrome responds to maintenance therapy, but the gingiva and oral mucosa continue to display an abnormal appearance with white patches. Histologic findings suggest that the junctional epithelium in Kindler syndrome may be abnormal and could explain why these patients have periodontal disease. Attachment loss progressed around teeth with an initial guarded or poor prognosis. Teeth that started with a good or fair prognosis continue to have a fair prognosis. Limited dental implant treatment is being considered.

Figure 1

The kindlin-1 protein with FERM and PH domains and regions of homology with filipodin and talin. Locations of reported positions of all loss-of-function mutations within the KIND1 gene are shown, including nonsense, frameshift, or splice mutations (indicated by arrows) but excluding large deletions. COOH = carboxylic acid.

Figure 2

Selective radiographic comparison of the bone levels 1 year after her initial treatment was completed (1997) and at the most recent complete survey (2004). Note the progression of bone loss around all of the maxillary molars, whereas some teeth with minimal bone support (remaining maxillary incisors) show no major alterations.

Figure 3

Clinical intraoral photographs reveal the thin lichenoid appearance of the gingiva (arrows) (A) and localized sites of spontaneous bleeding (arrows) (B).

Figure 4

Lack of expression of kindlin-1 RNA in cells cultured from a patient with KS. ST = 1-kb DNA ladder; bp = base pairs.

Figure 5

Histologic assessment of periodontal tissue of maxillary molars of the patient with KS. The teeth were removed gently with forceps, with a small amount of gingival tissue attached, and processed for routine histology. Atypical junctional/pocket epithelium was present in all specimens that showed proper morphology (three separate blocks shown in A, C, and D). In two specimens (A and C), the epithelium showed a blunt end with no attachment to the tooth surface. In one specimen (D), the end of the epithelium resembled epithelium migrating into a wound. Red blood cells (*) were visible in many samples, indicating trauma or spontaneous bleeding (as complained about by the patient). Heavy chronic inflammation was present in all specimens examined (A through D). The inflammatory infiltrates were often approaching the root surface deep in the connective tissue without the epithelial enclosure that is seen in classic periodontitis specimens (B, which represents a deeper area of the same specimen shown in A). Considering the extent of inflammation, the rete ridges were poorly developed or non-existent with signs of epithelial separation from the connective tissue (A, C, and D). T = tooth; E = epithelium; CT = connective tissue. Bars = 200 µm.