Isolated cleft lip with generalized aggressive periodontitis: A rare entity.

Oro-facial clefts are one of the most common birth defects and may be associated with other genetic anomalies. Aggressive periodontitis is a rare condition that progresses rapidly, but affects only a small percentage of the population. Most of the cases of aggressive periodontitis are familial. Even though, literature has documented the association of various genetic disorders with aggressive periodontitis, the aggressive periodontitis in patients with isolated cleft lip (CL) have never been addressed. Here, we report a rare case of isolated CL with generalized aggressive periodontitis. The concomitant presentation of isolated CL with aggressive periodontitis in an individual has clinical significance for multi-disciplinary care.

INTRODUCTION

A cleft is a fissure or opening due to the nonfusion of the body's natural structures that form prior to birth. An orofacial cleft is caused by an incomplete fusion of the maxillary processes from the 4 to 12 week of fetal life. It is one of the most common birth defect and is multifactorial in nature. The important etiologic factors are of genetic origin, determined by a monogenetic or polygenetic inheritance pattern as well as some exogenous factors, such as smoking, alcohol, X-rays and antimitotics.[1] The orofacial clefts were classified as isolated cleft lip (CL) only, complete bilateral cleft lip, alveolus, and palate, complete unilateral cleft lip, alveolus, and palate (left-cleft lip and palate (CLP) or right-CLP), isolated cleft palate (CP) only.[2] CL can is caused by failure of fusion of the maxillary and medial nasal processes during formation of the primary palate. It can be complete or incomplete, unilateral or bilateral. The prevalence of CL ± palate is reported as 0.5-2/1000 live births depending on the country's population. In India, the prevalence of CL ± palate is estimated as 0.93/1000.[3]

Genetic factors make strong hold for the occurrence of CL, and a number of genes are involved in its occurrence. A CL may be present as a single isolated defect or in association with a syndrome such as Van Der Woude syndrome, ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome, Patau syndrome acro-cardio-facial syndrome, Hay–Wells syndrome, popliteal pterygium syndrome and Malpuech facial clefting syndrome.[4] However, the majority of them are isolated defects and therefore termed as nonsyndromic defects. Nonsyndromic cases include particular sequence variants in the genes IRF6, PVRL1, and MSX1.[4]

The individuals with a CL and palate are at increased risk for the development of carious lesions and periodontitis. They have peculiar oral characteristics is such as tooth malpositioning, supernumerary teeth, hypodontia, microdontia, mucogingival alterations, xerostomia, and parotid duct atresia.[5] The persisting soft tissue folds before closure, which is difficult to reach with conventional cleaning techniques, and may serve as a habitat for putative pathogens, thereby enhancing the intraoral translocation of pathogens and consequently, the risk for periodontal disease.[6] The high incidences of plaque and bleeding on probing were reported in patients with CL and palate.[1] It could be due to the cleft deformity and surgical scars which make it difficult to control plaque. Recently, the EEC syndrome has been reported in association with the aggressive periodontitis.[7]

Aggressive periodontitis is an infrequent type of periodontal disease with rapid destruction of the periodontal attachment apparatus and supporting alveolar bone. The prevalence of aggressive periodontitis varies among ethnic groups and countries, and it may range from 0.1% to 3%. It is multifactorial in nature, the important etiologic factors are of genetic origin as well as other factors such as microbiologic, immunological and environmental.[8] Although, literature has documented the association of aggressive periodontitis with various genetic disorders,[8] it is never documented with isolated CL. This case report is apparently the first in literature to document isolated CL with the aggressive periodontitis. The clinical significance is that a CL may be associated with various syndromes that may in turn have oral manifestations. The individuals with a CL are at increased risk for development of periodontitis.[5] CL can involve the periodontal attachment apparatus and the supporting alveolar bone in its proximity and thereby contributing to periodontal destruction.

CASE REPORT

A 26-year-old female, 160 cm tall and weighed 47 kg presented to the Outpatient Division, Department of Periodontics, with the chief complaint of increased spacing between upper and lower anterior teeth since the last 2 years [Figure 1]. Occasionally, bleeding occurred while brushing teeth and hypersensitivity in lower anterior teeth with cold fluids. The patient's medical history revealed that she had a cleft on the right side of upper lip on at the time of birth. This cleft was a minor form of Tessier no. 1 cleft which is a paramedian, craniofacial cleft that traverses through the soft tissues from the Cupid's bow region to the alar cartilage, resulting in a notch in the dome of the nostril. She was operated at the age of 2 and 24 years [Figure 2] for surgical correction of CL. She was born as the first of two children of nonconsanguineous parents after uncomplicated 37 weeks of gestation. Intelligence and other developmental milestones were normal. There was no history of absent or decreased sweating. Past dental history revealed she had congenitally missing teeth in upper and lower jaw. She had undergone root canal treatment with the lower right first premolar 5 years back. She had not taken any medication in past 1-year and has no known allergies. She gave a family history of her mother losing all her teeth at an early age due to mobility of teeth. Her 24-year-old younger brother also had a history of periodontal disease and treated with periodontal flap surgery, but her father was normal. It was observed that there was familial history for periodontal disease. She had nasal twang in her voice, long nails without any gross digital anomaly, sparse eyebrows, mild hypertelorism, potentially incompetent lips and a scar mark on right upper lip area [Figures 1 and 3].

Figure 1

Female patient with scar mark on right upper lip area, sparse eyebrows, mild hypertelorism and potentially incompetent lips

Figure 2

(a) Cleft lip scar before second repair surgery; (b) Postoperative view of cleft lip

Figure 3

Hand and feet with long nails and absence of any gross digital anomaly

Oral examination

Federation Dentaire Internationale tooth notations were used during the oral examination. On oral examination, the status of oral hygiene was fair. Oral examination does not reveal any soft tissue defect on labial mucosa, palate, and gingiva [Figure 4]. Patient had 29 teeth of which 23, 31 and 41 were congenitally missing [Figure 4]. Probing pocket depth and clinical attachment loss measurements were performed on each tooth using a graduated William's periodontal probe. Greater probing pocket depth (>6 mm) and clinical attachment loss (>3 mm) measurements were noticed with respect to teeth no. 17, 16, 13, 12, 11, 21, 22, 26, 27, 34, 36, 37, 44, 46 and 47. Grade I mobility was present with respect to teeth no. 11, 21, 26 and 34. Pathologic migration was present with respect to teeth no. 11, 21, 31and 41. Increased anterior overjet and spacing were present. The patient had Class I molar relation on both sides.

Figure 4

(a-e) Oral examination; (f) Absence of any soft tissue defect on labial mucosa

Investigations

Following investigations were carried out:

Panoramic radiograph which revealed angular pattern of bone loss around 16, 12, 11, 22, 26, 37, 34, 44 and 46. Typical “arc shaped” loss of alveolar bone around maxillary molars and incisors was observed [Figure 5]

Figure 5

Panoramic radiograph

Blood investigations which were found to be within the normal ranges except for borderline neutrophilia [Table 1]

Table 1

Blood investigations

Neutrophil function test which revealed hyperactivity in nitroblue tetrazolium test, reduced chemotaxis and reduced phagocytosis with normal intracellular killing [Table 2]

Table 2

Neutrophil function test

Subgingival plaque sample was collected from the deepest pocket followed by microbiological culturing on Dentaid medium and blood agar with hemin and vitamin K. Dentaid is a selective culture medium for Aggregatibacter actinomycetemcomitans and blood agar with hemin and vitamin K is for anaerobic micro-organisms. Minute black colonies (3 × 104 CFU/mL) of Porphyromonas gingivalis were observed [Figure 6].

Figure 6

(a) Subgingival plaque sampling. (b) Microbiological culturing

Based on the family history, oral examination, radiographic details, microbiological culturing, and immunological parameters (neutrophil function test) a diagnosis of generalized aggressive periodontitis was made.

Treatment

The overall treatment was aimed at correction of increased spacing between upper and lower teeth and maintenance of oral health. It included multi-disciplinary approaches such as periodontal treatment, restorative treatment for the replacement of fixed dental prosthesis, and fixed mechano-therapy along with the opinion of plastic surgeon, endodontist and oral and maxillofacial surgeon for long-term maintenance of oral health. Periodontal treatment for aggressive periodontitis was aimed at eliminating or reducing the pathogenic micro-organisms and prevention of further bone loss. It included mechanical treatment (scaling and root planning) along with systemic antimicrobial therapy followed by periodontal flap surgery and supportive periodontal treatment at regular intervals.[8]

DISCUSSION

This case represents presentation of isolated CL with generalized aggressive periodontitis for the first time in the literature. The incidence of CL has been influenced by gender, ethnic and racial backgrounds. Isolated cleft of lips are seen more commonly in males and on the left side.[4] On the other hand, in our report isolated CL was present in female on the right side, which was again a rare finding. The CL has been classified as Tessier no. 0-14 clefts based on the extension of cleft and its association with other oral, nasal, orbital and auricular anomalies.[9] Present case had a minor form of Tessier no. 1 cleft which was corrected surgically. Tessier no. 1 cleft may continue through the alveolus between the central and lateral incisors that could have periodontal implications. In such defects, the radiographic alveolar bone level is more apical at the cleft sites than that at noncleft sites.[10] The osseous structures are absent or poorly developed in the cleft area and are additionally traumatized in the course of long-term orthodontic therapy. However, the present case does not reveal any such defect near the cleft area in the radiograph [Figure 5].

An individual with CL has to deal with the typical challenges related to self-esteem, appearance and social acceptance due to associated anomalies. Venkatesh[11] in 2009 showed out of the 2600 orofacial cleft patients, only 198 had associated anomalies. Associated anomalies were more frequent in patients with CL and palate (32%) than in patients with isolated CP (22%) or patients with isolated CL (11%). The prevalence of associated anomalies in subjects with isolated CL was very low. This could be a reason why no major associated anomalies have been detected in the present case. Thus, the present case could be either a partially expressed syndromic cleft or a coincidental nonsyndromic “isolated” cleft.

Ectrodactyly-ectodermal dysplasia-cleft syndrome (EEC syndrome) is an autosomal dominant disorder characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefting.[7] In the present case, mild over extension of fingers and sparse eyebrows were found. The nails and hairs were long enough, without any digital anomaly. Thus, ectrodactyly and ectodermal dysplasia were ruled out. The other syndromes[11] include Van Der Woude syndrome, which is characterized by the combination of lower lip pits, CL or CP, hypodontia, syndactyly, congenital heart disease and cerebral abnormalities. Hay wells syndrome is characterized by ankyloblepharon filiforme adnatum, CL or palate and ectodermal defects. Popliteal pterygium syndrome is characterized by malformed toenails, CL or palate and genital findings.

Genetic factors make strong hold for occurrence of nonsyndromic “isolated” CL. However, no single gene has been identified as a necessary locus for the development of nonsyndromic clefts. Rather, the emerging consensus is that the genetic etiology of nonsyndromic clefting is complex, with several loci showing significant results.[12] Therefore, chromosomal analysis for the identification of gene locus for development of nonsyndromic clefts was not undertaken as it could be inconclusive.

Hypodontia is commonly found in CL patients and was one of the important finding in our report. The subjects with orofacial cleft were at a higher risk for periodontal disease progression. A cleft site tends to experience more periodontal tissue destruction compared with control sites.[13] The teeth adjacent to the cleft often with a long supra-crestal connective tissue attachment, showed a slightly more pronounced periodontal destruction.[14] In the present case, teeth in the cleft area as well as contralateral noncleft area showed greater loss of attachment loss(>3 mm) and bone. The present case showed (1) Noncontributory medical history and positive family history of periodontal disease, (2) rapid bone destruction, (3) fair oral hygiene that revealed inconsistency between microbial deposits and severity of destruction, (4) generalized attachment loss that affected at least 3 permanent teeth in addition to the first molars and incisors, and (5) radiographic finding of angular bone defects (6) Neutrophil defect. Therefore, in this case the diagnosis of generalized aggressive periodontitis was made with coincidental finding of isolated CL.

In aggressive periodontitis, the highly progressive and destructive bone loss around the teeth have developed in a short span of time. Various periodontal pathogens have been implicated in sites of aggressive periodontitis, but the role of A. actinomycetemcomitans has been the predominant one.[8] In this case, subgingival plaque showed high titers of P. gingivalis, which is a known virulent periodontopathogen [Figure 6]. This finding indicates microbiologic heterogeneity exist for aggressive periodontitis. Defect in neutrophil function was observed, which included reduced chemotaxis and phagocytosis [Table 2]. This indicates a reduced defensive ability against the periodontal pathogens. Factors other than virulent micro-organisms surrounding the tooth in the dental plaque could have influenced the actual clinical presentation. The genetic component makes a strong hold for occurrence of aggressive periodontitis, and it follow a dominant mode of transmission.[8] On the other hand, autosomal recessive mode of transmission has also been noted for aggressive periodontitis.[15] This indicates that both etiologic as well as genetic heterogeneity exist for aggressive periodontitis. Since the genetic factor is an important etiologic factor in both conditions. This issue begs further research to determine the genetic status of such patients to comment on the relationship between these two entities. The present case of isolated CL with generalized aggressive periodontitis requires an early multi-disciplinary approach to achieve long-term oral health and to prevent further periodontal disease progression.

CONCLUSION

The concomitant presentation of isolated CL and aggressive periodontitis in an individual has clinical significance for multi-disciplinary care. Further research is required to determine the genetic status of such patients to identify any relationship between these two entities.