A Rare Case of Hypodontia in Kawasaki Disease: Review of the Literature and Case Report

Kawasaki disease (KD) is a rare idiopathic infantile multi-organ vasculitis of medium-sized arteries that predominantly affects children younger than the age of 5 years. Besides the persistent fever of 5 or more days and among the typical criteria for the diagnosis of KD, a dentist may encounter oral manifestations such as “strawberry tongue”, red or dry fissured lip and oropharyngeal erythema. If left untreated, the disease may have fatal prognosis due to the involvement of vital organs. Hypodontia belongs to the most common congenital anomalies in humans. Genetic studies suggest both genetic and environmental etiology toward this anomaly. It is frequently associated with other oral anomalies and altered craniofacial growth. Different health problems have been observed in patients with hypodontia. In the literature, the finding of hypodontia in KD is very rare. This article aims to report a case of a Caucasian 8 year-old boy with hypodontia, who was treated in the age of 7 months for KD. A short review of the literature regarding the two conditions is presented. *Corresponding author: Evangelia K. Chatzistavrou, DDS, MSc, DrDent, Orthodontist, Private practice, 5 Agias Theodoras Str., GR 546 23 Thessaloniki, Greece, Tel: +3


Introduction
Changes in the number of teeth characterize the most common congenital anomalies in humans [1,2]. Tooth agenesis is the congenital lack of one or more permanent teeth. In the case of lack of up to 6 teeth, this anomaly is called "hypodontia", either mild or moderate. When the number of missing teeth is more than 6, excluding the third molar, the condition is characterized as severe hypodontia. The terms "oligodontia" (i.e. a few teeth present) and "anodontia" (i.e. complete lack of teeth) are rather historical [3]. The prevalence of hypodontia is reported to vary between 2.6 and 11.3 per cent, depending on demographic and geographic profiles [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. There is also a preference for women compared to men [18]. Clinicians often claim that dental agenesis is increased during recent decades [19,20]. There is no evidence, though, as to whether this is an evolutionary trend or an observation, as a result of more advanced screening and diagnosis of oral anomalies in general. In the permanent dentition (excluding third molars), mandibular second premolars are the most frequently missing teeth, followed by the maxillary lateral incisors and second premolars [20][21][22].
Tooth agenesis may be classified as syndromic/non-syndromic and familial/sporadic. While the nature of syndromic or familial agenesis provides information on mechanisms of the disease, nonsyndromic and sporadic agenesis is of special interest due to the lack of apparent mechanism underlying its induction. In the majority of cases, hypodontia has genetic causes. The contribution of genetic factors to dental agenesis has not been clarified yet [54], although a significant progress has been made in the understanding of the mechanisms involved. Moreover, the pathogenesis of hypodontia cannot be explained by genetic factors alone, since monozygotic twins show discordant expression at a certain frequency with respect to hypodontia [55]. The disease is thought to have a connection with some environmental factors, such as infection (e.g. rubella) [56], the use of certain chemical substances and drugs during pregnancy, chemo-and radiotherapy [54][55][56][57]. Different kinds of trauma in the apical area of the dentoalveolar processes (fractures, extraction of temporary tooth) may also contribute to the pathogenesis of tooth agenesis [4]. However, the environmental aetiology of hypodontia is not yet fully understood.
On the other hand, according to the results of a retrospective study in a population of Japanese orthodontic patients, predisposing general health problems, especially allergy, seem to be involved [58]. General health problems observed more frequently in patients with hypodontia include allergy, enlarged adenoids, asthma, atopy, bronchitis, stuffy nose, exudative otitis media, Basadow's disease, atelectasis, acute lymphocytic leukaemia, epilepsy, haemangioma, hydrocephalus, infectious mononucleosis, neonatal jaundice, liver cancer, low birth weight, pyloristenosis, rubella, sialolithiasis, varicella and Kawasaki's disease [58].
Kawasaki disease (KD) is an acute self-limited vasculitis of unknown etiology that affects predominantly infants and children younger than 5 years of age. It was first described as Mucocutaneous Lymph Node Syndrome (MLNS) by the Japanese pediatrician Dr. Tomisaku Kawasaki who in 1967, diagnosed 50 cases, in which a rash and fever in early childhood were accompanied by edema, conjunctival infection, redness and cracking of the lips, "strawberry tongue", convalescent desquamation, and occasionally lymphadenopathy [59,60]. KD is considered a kind of systemic vasculitis syndrome that primarily invades the medium-sized muscular arteries including coronary arteries [61]. Despite the fact that the disease is mostly prevalent in Japan and East Asian countries (with an annual incidence of about 112 cases per 100,000 children<5 years old), it has been reported all over the world and is now known to occur in both endemic and communitywide epidemic forms in the United States, Europe and Asia, in children of all races [62]. Epidemiologic data suggest that susceptibility to KD depends more upon racial factors than geographic reasons [63]. It affects boys more often than girls (1.5:1 male: female ratio) [64,65] and, although it occurs year round, cases tend to cluster in the winter and spring [64].
Diagnosis of KD is based on the presence of fever persisting for 5 days or more, associated with other transient typical signs, that rarely is simultaneously present at the time of first observation, but can appear subsequently [66]. These symptoms are bilateral conjunctival congestion, redness of the lips and oral mucosa, polymorphous skin rashes, reddening of the palms and soles followed by membranous desquamation and acute non-purulent cervical lymphadenopathy [61]. The most serious complications are coronary artery aneurysms or ectasia which develop in 15-25% of untreated children with the disease and may lead to myocardial infarction, sudden death, or ischemic heart disease [62].
The average duration of Kawasaki disease is 6-8 weeks and is characterized by 3 phases. Most signs and symptoms appear during the initial acute febrile phase, which lasts 1-2 weeks. The subacute phase follows after, until approximately day 25, where desquamation, arthritis and althralgia occur with elevated platelet counts. Finally, during the convalescent phase, the clinical signs and symptoms disappear. Management of KD is aimed at reducing inflammation in the myocardium and the coronary arterial walls during the acute phase of the disease, and preventing coronary thrombosis. It involves the administration of intravenous immunoglobulin (IVIG) and high-dose aspirin as soon as the diagnosis is made [62].
The purpose of this article is to report a case of a Caucasian boy with hypodontia who was treated in the age of 7 months for Kawasaki disease and has not had any related or other general health problems since. A short literature on both conditions is presented.

Case Presentation
An eight year-old Caucasian male was presented by his parents to the Orthodontic Department of the Dental School of the Aristotle University of Thessaloniki, in Greece. The patient's chief complaint was "the gaps between his teeth". According to his medical history, the boy was successfully treated in the age of seven months for Kawasaki disease and has not had any related or other general health problems since. No similar medical anamnestic data were reported in the family regarding Kawasaki disease and/or hypodontia. The facial extraoral examination revealed a straight profile type and a small asymmetry of the lower third of the face, because of a slight deviation of the chin to the left (Figures 1a and b). Intraoral examination and study models indicated early mixed dentition, Class I molar relationship, an overjet of 1 mm, an openbite of -3 mm, unilateral posterior crossbite on the right side and a functional shift of the mandible due to premature contacts of the primary canines on both sides (Figures 2a-c). Oral hygiene was of a moderate standard, with staining mainly on the posterior dental surfaces. The pretreatment panoramic radiograph (Figure 3) revealed six permanent teeth missing-all four second premolars, upper left first premolar and upper right lateral incisor-indicating a case of hypodontia. The cephalometric analysis of the pretreatment lateral cephalometric radiograph (Figure 4), showed normal growth pattern, straight profile of the hard tissues, small cranial base length, retrognathic maxilla and prognathic mandible, with a slightly bigger mandibular body and the   chin projecting in a more forward position. Lower incisors were not retroclined but were relatively forward positioned in relation to their osseous base, whereas upper incisors were normally inclined. No dental or osseous lesions were detected in the above radiographs. The aim of the patient's treatment was the correction of his malocclusion and the preparation of the mouth for future prosthetic work, due to the multiple missing teeth. This involves a multidisciplinary approach, comprising of the cooperation of an orthodontist and a prosthodontist. The orthodontic treatment plan consists of a Hyrax appliance combined with a Delaire face mask for the correction of the skeletal malocclusion, and fixed orthodontic appliances to arrange the teeth in the most proper position to receive the future prosthetic restoration. The finalized prosthetic rehabilitation will take place upon completion of growth of the young patient.

Discussion
KD is a disease that may affect the patient's general health in multiple ways and cause several serious systematic disturbances. It usually appears at an early age, coinciding with the age of tooth formation. In the literature, there is only one study reporting that KD belongs to a group of general health problems that has been found to co-exist with hypodontia. In total of 3683 Japanese orthodontic patients, 215 had hypodontia and only one of those had been sick with KD in childhood. The above study aimed to identify the etiological factors underlying hypodontia by investigating the general health problems of Japanese orthodontic patients with hypodontia. However, the association between the two conditions could not be clarified [66].
Hypodontia creates esthetic problems, may cause masticatory and speech dysfunctions and is a matter of concern to most parents. A dentist is the first person to identify the problem of hypodontia and is the one who first determines the type of the inheritance pattern. This is the reason why it is of great importance to take a comprehensive medical history. The knowledge of a combined medical situation will enable the health professional in rendering the appropriate treatment to improve the esthetics. All medical conditions should be accurately understood before any treatment is planned. Patients and their parents should be well informed of all the options; in so, an ideal treatment plan can be formed for their benefit.
In the literature, only recently, KD has been related with lip swelling as a late symptom [67]. It should be wise for the dentists to be suspicious and alert with the oral manifestations of KD as they might be playing an important role in the early diagnosis of this rare disease. In children with medical history of the Kawasaki disease, and in need for dental treatment, a possible antibiotic prophylaxis would most probably be required before the intervention of the dental practitioner. In such a case, the doctor following the KD patient should prescribe the appropriate antibiotic medication.
The case presented is a rare report of hypodontia in a KD patient. It is important though, because of our limited present knowledge regarding the etiology of hypodontia, to report every health condition that has been found and might be related to it. Moreover, this is also a rare case of Kawasaki disease, due to the sparseness of the specific condition in Europe.