Fragile X Syndrome: A Rare Case Report with Unusual Oral Features.

Fragile X syndrome (FXS) is a rare variant of special health-care need demonstrating delayed developmental milestones and associated with intellectual and emotional disabilities ranging from learning problem to mental retardation. The syndrome is usually not diagnosed until 8-9 years of age since the clinical manifestations of the syndrome are greatly attenuated in childhood. The physical characteristics such as facial features, hyperactivity, attention deficit, autistic behavior, and macroorchidism are quite evident in younger age group. The most typical orofacial characteristics associated with children suffering from FXS are mandibular prominence, ogival, and cleft palate. Till date, very few dental literatures have been reported regarding the association of FXS with orodental anomalies. Here, we report a rare case of 14-year-old boy suffering from FXS with typical orofacial characteristics, multiple supernumerary teeth, and dental caries.

Introduction

Fragile X syndrome (FXS) also known as Martin-Bell syndrome is the most common inherited cause of mental retardation affecting approximately 1 in 4000–6000 male and 1 in 8000–10,000 female.[1] The syndrome is associated with a fragile site at Xq27.3 and an abnormality of the FMR1 gene.[2] This alteration originates from an increase in the number of repetitions of the cytosine-guanine-guanine trinucleotide. Since the mutation is X-linked, males are more severely affected than females and males with FXS predominantly exhibit mental retardation, with characteristic physical features and behavioral alteration.[3] The predominant clinical manifestations of this syndrome include an elongated and narrow face with a large forehead with frontal bossing and prominent chin, large and anteverted ears, hypotelorism, strabismus, hypoplasia of the middle third of the face, mandibular protrusion, and the possible coexistence of Pierre-Robin syndrome, joint hyperlaxity (with increased mobility), and unilateral or bilaterally large testes (macroorchidism). The most frequent intraoral anomalies are an ogival palate, cleft palate, the presence of mesiodens, dental hypomineralization, and abrasion of the occlusal surfaces and incisal edges as well as an increase in the dimensions of the dental crowns in the mesiodistal, and cervicoocclusal orientation, which produces severe bone-dental discrepancies.[4]

This case report highlights the presence of multiple supernumerary teeth and other orodental finding in maxillary and mandibular arch along with characteristics physical features of FXS in a 14-year-old boy.

Case Report

A 14-year-old boy referred by general dental practitioner to the Department of Pedodontics and Preventive dentistry, SCB Dental College and Hospital, Cuttack, Odisha, India, with a chief complaint of multiple teeth (extra teeth) in both upper and lower jaw. On clinical examination, it was observed that the child exhibit behavioral disorders with autistic features. Extraoral features revealed an elongated and narrow face with a large forehead and prominent chin [Figure 1]. Intraoral examination revealed multiple supernumerary teeth in relation to both upper and lower dental arch, crowding, high-arch palate, macroglossia, cleft of palate, and multiple carious teeth [Figure 2 and 3]. Panoramic radiographic evaluation revealed the presence of multiple teeth in the anterior region of both maxillary and mandibular dental arch with congenital absence of teeth in relation to 18, 28, 38, and 48 [Figure 4]. Parental history revealed that the child was delivered at term by lower segment cesarean section with a birth weight of 3.6 kg. He did not cry immediately after birth, and hence, referred to Neonatal Intensive Care Unit for the further management. He subsequently developed neonatal jaundice, for which treatment was assumed and discharged after 20 days. General physical examination revealed some typical characteristic features such as an elongated face, prominent frontal bone, hypotonia, hyperlaxity of the ligaments and cognitive deficiency. Pubertal stage was Tanner stage V with bilaterally enlarged testis (macroorchidism) with testicular volume >30 cc using Prader orchidometer beads. There is a family history of mental retardation in his sibling. Due to the presence of mental retardation and characteristics somatic features along with macroorchidism, a clinical diagnosis of FXS was ascertained with further consultation with endocrinologists. However, due to lack of feasibility of genetic testing, it could not be performed in this case. Extraction of supernumerary teeth was planned after seeking an opinion from the Department of Endocrinology, Cardiology, and Otolaryngology.

Figure 1

Extraoral view revealed an elongated and narrow face with a large forehead and prominent chin

Figure 2

Intraoral view revealed multiple supernumerary and carious teeth in relation to both upper and lower dental arch

Figure 3

Intraoral view of lower dental arch

Figure 4

Panoramic radiographic revealed the presence of multiple teeth in the anterior region of both maxillary and mandibular dental arch with congenital absence of teeth in relation to 18, 28, 38, and 48

Discussion

FXS was first described in 1943 by J. Purdon Martin and Julia Bell. Genetic origin was established in 1969, when individuals with certain mental and physical characteristics were reported with an alteration of chromosome X. The association of FMR1 gene with FXS has been described by Verkerk in 1991.[4] Children with FXS have delayed developmental milestones and delayed mental development is usually the first diagnostic sign. The syndrome is usually not diagnosed until 8–9 years of age since the clinical manifestations of the syndrome are greatly attenuated in childhood. On puberty, the facial and body features of FXS become more evident, and testicular enlargement is observed (although 10%–15% of all affected boys present macroorchidism before puberty). A proposed clinical checklist of characteristics features of FXS may be helpful for the clinical diagnosis of developmentally delayed children [Table 1].[2] The patient reported in our case was in pubertal stage displaying attenuated facial features, mental retardation, autistic behavior, and macroorchidism. The most typical orofacial characteristics of FXS patient are mandibular prominence, ogival, and cleft palate which was also reported in our case. Other typical findings as reported by Nunn et al. and Shellhart et al. are abrasion of the occlusal surfaces and incisal edges of the teeth, but in our case, there was no evidence of occlusal wear facets and enamel hypoplasia. This can be attributed to the young age of the child.[4] The presence of supernumerary tooth in the premaxillary region was reported by Kulkarni et al., but there is a paucity of literature regarding the presence of supernumerary teeth in both dental arches which was quite evident in our case.[5] The conditions commonly associated with multiple supernumerary teeth include cleft lip and palate, cleidocranial dysplasia, and Gardner's syndrome but the association with FXS is rarely reported. DNA analysis such as Southern blot analysis and polymerase chain reaction can be a reliable diagnostic test for the detection of FXS.[3] Confirmatory genetic tests were not performed in our case due to low socioeconomic status and its insignificant prognostic value in the further management of the patient. The presence of characteristic orofacial alterations in children of male gender suffering from mental retardation of unknown origin provides an initial clinical diagnostic clue for the dental professionals to establish FXS as a special interest in dentistry.

Table 1

Checklist combines suggestive and common clinical findings as reported in this case reports and previous studies

Conclusion

This is a rare case report of FXS displaying association of this syndrome with multiple supernumerary teeth in both maxillary and mandibular arch. Any behavioral disorders with such characteristics orodental findings may be a potential candidate of FXS. Early diagnosis and prompt intervention can lead to a better quality of life in children suffering from behavioral disorders.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.