Gardner’s syndrome, a variant of Familial Adenomatous Polyposis (FAP), is a genetic disorder with highly penetrant autosomal-dominant transmission (80-100%). The incidence of FAP is approximately 1:7500 births [1,2], while Gardner’s syndrome occurs in 1:14000 births [1,3].
The first researcher reporting a clinical case characterized by the presence of manifestations which could be ascribed to Gardner’s syndrome was Fitzgerald in 1943 [4-6], however, the combination of these signs was recognized as a genetically determined syndrome only in 1953 by Gardner e Richards [4,7,8]. This disease is characterized by the following triad: Gastrointestinal polyposis, with a 100 percent chance of malignant degeneration [1,9-12]; other signs are bone tumors, frequently located on maxillary and cranial bones, and lastly the soft tissues tumors. Other extra-intestinal manifestations include retinal lesions, dental anomalies and other malignant neoplasms.
Gardner’s syndrome should enter in differential diagnosis with odontogenic tumors, Cowden syndrome and Peutz-Jeghers syndrome. The importance of an early diagnosis lies in the high malignant potential of this syndrome. In this light, the dentists and the maxillofacial surgeons should be able to recognize the signs of this syndrome, which frequently occurs in the head-neck region and are often the alarm bell of this unrecognized disease.
Aim of this report is to show how a careful dental examination and a proper medical anamnesis are the way to early diagnosis of Gardner's Syndrome: The correct clinical diagnosis could lead to further tests in order to verify other most pathogenic aspects related to this syndrome.
A 23 year old female patient reported pain in the right mandibular molar region. The extraoral examination showed the presence of a slight swelling at the level of the right mandibular angle and a reduction of the mandibular movements.
The intraoral examination revealed the persistence in the dental arches of two deciduous teeth, with some permanent elements retained; furthermore, enamel hypoplasia in all the teeth was clinically observed. X-rays panoramic showed the presence of impacted third molars, and in the intraosseous area close to the molar 48, it was evident a radiolucent zone which suggested an inflammatory process of periodontal sac, with a probable bacterial infection that would justify the mandibular edema, as reported by the patient (Figure 1).
During general anamnesis, the patient referred irregular bowels, with occasional blood loss in feces; further informations highlighted that her father had a total colectomy and her paternal grandfather died of colorectal carcinoma.
On the basis of the clinical data and the family medical history, we hypothesize the diagnosis of Gardner’s syndrome.
On our recommendation, the patient performed endoscopic examination of colon, which showed the presence of multiple polyps (Figure 2), spread on the whole length of the colon.
Histological investigations of polyps tissue revealed they were tubule-villous adenomas. The gastroenterologists advised the patient to undergo colectomy. It was decided to perform a genetic screening: this examination revealed an alteration in the 5q21 locus of the APC gene, which confirmed our diagnostic hypothesis. The patient was suggested to have regular specialist examinations.
In relation to the dental treatment, we have opted for the extraction of 48 (Figure 3), followed by antibiotic therapy.
Subsequently, the residuals deciduous teeth were extracted, and orthodontic treatment was planned to reposition in the dental arch her teeth not yet erupted. Patient is still under periodical follow-up.
Gardner’s syndrome is a genetic disease presenting high incidence of malignant degeneration [1,13]. Spontaneous mutations of the APC gene (adenomatous polyposis coli), which is located on the long arm of chromosome 5q21-q22 [4,14], represent the genetic predisposition toward the development of colorectal carcinoma, according to Volgestein researches .
Gardner’s syndrome has been usually associated with a triad of symptoms: Polyposis of the gastrointestinal tract, bone tumors and soft tissue tumors (desmoid tumors and epidermoid cysts). It also includes other extra intestinal manifestations, such as retinal lesions, dental anomalies and other malignant neoplasms.
The first symptoms of colorectal involvement are usually diarrhea, rectal bleeding and mucus discharge, similarly to what has been reported in this report. The treatment is surgical and involves colectomy [1,16]. The extra intestinal manifestations can occur many years before the onset of the intestinal polyps, which are often pauci symptomatic .
Therefore dentists, radiologists and internists should be aware of the manifestations of this disease, in order to identify itearlier and to start with the proper follow-up of patients at risk.
Osteomas are benign bone tumors which occur more commonly on the cranial vault (especially on frontal and occipital bone), and on the maxillary bones, especially the mandible. In the latter, the most affected areas are the lingual side of the body, the angle, the lower edge and the condylar region, causing facial asymmetry [4,17]. They can also affect the maxillary and frontal sinuses. They manifest in 62-80% of patients with Gardner’s syndrome and the average number of osteomas varies between 2,9 and 5,9 [4,18]. They can reach a considerable size (over 3cm). The presence of multiple areas of bone thickening represents an alarm bell which should lead the clinician to take a thorough family medical history, and perform the appropriate radiological follow-up and genetic screening for the APC gene . The treatment recommended for this disease is the surgical excision of osteomas of considerable size, responsible for functional or esthetic problems.
Other neoplasms that occur with a higher incidence, compared to the general population, are thyroid carcinoma, suprarenal carcinoma, biliary pancreatic adenoma, hepatoblastoma and malignant tumors of the central nervous system . The papilliferous adenocarcinoma of the thyroid tends to be multicentric and can precede the identification of colon polyps or occur after colectomy. Owing to the high incidence of metastasis and mortality, it becomes important a thorough diagnostic screening at reguar intervals, comprising neck palpation, ultrasound scan and, if necessary, a fineneedle aspiration biopsy (FNAB) .
Patients with Gardner's syndrome show orofacial anomalies in about 75% of cases: The most frequent clinical sign are the osteomas which are present in 30-75% of syndromic patients. Osteomas can affect both the maxillary bones, as well as other cranial bones .
The most frequent dental anomalies include supernumerary teeth, multiple dental impactions, dental agenesis, fused roots, malpositions and malformations; resorption of roots adjacent to a supernumerary may occur but it is extremely rare .
In addition to this, it is possible to find odontogenic tumors, dentigerous cysts, multiple caries [10,11]. Dental anomalies have a higher incidence in patients affected by Gardner’s syndrome compared to the general population: In a recent study, dental impactions were found in 11 (37,9%) out of the 29 patients affected by Gardner’s syndrome . A study by Chattopadhyay and Mahesh Chander showed patients that reported facial asymmetry, with a severe limitation of mouth opening and difficulty in speech because of intraoral location of tumors .
Finally, dentists must consider the cases in which oral and maxillofacial abnormalities could lead to the involvement of both bone and cemental proliferations .
With the described analysis, the Authors want to stress the importance of an adequate knowledge of the common manifestations of Gardner’s syndrome, particularly in the head-neck area, that dentist and maxillofacial surgeon must have.
The importance of an early diagnosis, even in all those atypical cases, such as reported in this case report, lies in the potential fatal outcome of some clinical conditions related to Gardner’s syndrome.
The involvement of the head-neck region often represents the first clinical manifestation of Gardner’s syndrome and, therefore, it is the duty of the dentist to orient the patient towards an adequate diagnostic course, comprising a detailed family medical history, an appropriate radiological follow-up with radiographic examinations of maxillary bones, cranium and intestinal tract by means of a clysma. Finally, genetic screenings for the mutation of APC gene and, lastly, a biopsy and histological examination of the intestinal polyps could save the patient’s life.
Conflict of Interest
The authors declare that they have no competing interests.
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