Dental management of a patient with 22q11.2 deletion syndrome (22q11.2DS)

Abstract

22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes, with an incidence of approximately 1/2000–1/4000 live births; it is thought to be mainly attributable to a de novo deletion. The clinical phenotype of this syndrome is highly variable. Certain craniofacial and oral features are common to most patients with 22q11.2DS, including a high prevalence of dental caries; abnormalities of tooth shape, eruption and number; and enamel defects such as hypomineralisation and hypoplasia. This report focuses on the dental features and management of an 8-year-old boy with 22q11.2DS. Dental treatments were carried out under general anaesthesia. In summary, facial dysmorphism and common dental manifestations are typically noticeable in patients with this syndrome. Therefore, dentists need to be aware of the dental features of this condition in order to refer them to the adequate specialists. Cooperation among and experience with different specialties are mandatory to improve quality of life for patients with 22q11.2DS.

Background

22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes and presents with a highly variable phenotype. It is also known as DiGeorge syndrome, velocardiofacial syndrome, Shprintzen syndrome or CATCH 22.¹ The prevalence of this condition is estimated to be 1/2000–1/4000 live births.²

This condition is caused by a microdeletion of chromosome 22, which can be discovered via fluorescence in situ hybridisation, multiplex ligation-dependent probe amplification (MLPA), or chromosomal microarray. Approximately 93% and 7% of probands have a de novo deletion and an autosomal-dominant inherited deletion, respectively. However, children of patients with 22q11.2DS have a 50% chance of inheriting the 22q11.2 deletion.³ Most patients with 22q11.2DS (85%) have a large (3 Mb) deletion encompassing approximately 40 genes, including the TBX1 gene, which is responsible for the typical features of this syndrome.⁴

The clinical phenotype of 22q11.2DS is highly variable and includes >180 clinical features, although there is no single symptom present in all cases.⁵ The most common findings are congenital heart disease; palatal abnormalities, particularly velopharyngeal insufficiency; thymus hypoplasia with immune deficiency; hypocalcaemia due to hypoparathyroidism; and central nervous system (CNS) impairment that can result in learning disabilities, intellectual disability and abnormal behaviour. Craniofacial features are regarded as minor findings in patients with 22q11.2DS but are present in most cases.⁶ Individuals with this syndrome have numerous dental characteristics, including abnormalities of tooth shape, eruption and number as well as enamel defects such as hypomineralisation and hypoplasia. Oral manifestations also include a high prevalence of dental caries.⁷

Dental and craniofacial characteristics are thought to arise in most individuals with 22q11.2DS.^{6 8} Given these features, dentists need to be aware of the dental features of this condition in order to refer them to the adequate specialists, if needed. Early detection will allow dentists to start preventive programmes and reduce the risk that the patient will develop dental diseases.

This report describes and discusses the dental features and management of an 8-year-old boy with 22q11.2DS with manifestations that included severe open bite and ectopic eruption. In addition, a review of published literature on the dental characteristics and management of 22q11.2DS was conducted. Publications were searched using MEDLINE, which was accessed via the National Library of Medicine PubMed interface (http://www.ncbi.nlm.nih.gov/pubmed). The key words used in this search were ‘dental 22q11.2 deletion syndrome’. Articles that focused on the dental characteristics of 22q11.2DS and were written in English were included. Among the 32 articles retrieved and reviewed, only 11 articles were directly related to our topic. The ‘Related Articles’ feature of PubMed was also used to identify further references of interest during the course of the primary search.

The aim of this report was to highlight the most common dental features of 22q11.2DS to help paediatric and general dentists with the early detection and management of children with 22q11.2DS.

Case presentation

Accompanied by one of his parents, an 8-year-old Saudi boy visited the paediatric dental clinic at Alnoor Specialist Hospital, Makkah, Kingdom of Saudi Arabia, in December 2017. The patient presented with a chief complaint of open bite and decayed teeth. His parents and male sibling were generally healthy. The patient was born at full-term via vaginal delivery, with no complications. His vaccinations were up to date.

According to the patient’s medical history, at the age of 9 months, he was diagnosed with congenital oesophageal stricture with dysphagia and feeding problems; accordingly, endoscopic balloon dilatation was performed. At the age of 3 years, he developed mild hypocalcaemia and T-cell dysfunction, and his craniofacial abnormalities became more obvious; therefore, the treating physician suspected 22q11.2DS and ordered genetic consultation. The results showed that the patient had a 2.8 Mb microdeletion of 22q11.21. At the age of 5 years, he underwent another endoscopic dilatation procedure to stretch the oesophagus and relieve dysphagia. However, a complete medical evaluation revealed oesophageal stenosis, mild hypocalcaemia, intellectual disability, mild immunodeficiency with frequent infections of the upper respiratory tract, right conductive hearing loss, left sensorineural hearing loss, language disorders and craniofacial abnormalities.

The patient had a single visit to a general dentist at the age of 5 years. However, the experience described here was his first visit to a paediatric dentist. On physical examination, he was consistently below the 5th percentile on an appropriate growth chart, although his growth hormone levels were normal. Overall, the patient was asymptomatic and in good general health. He was reluctant to accept treatment, and evidence of a negative attitude was observed.

Clinical extraoral examination revealed a convex facial profile, a bulbous nasal tip, increased lower facial height, retrognathic posture of the mandible, hooded eyelids and protruding ears (figure 1). The child’s oral cavity exhibited mixed dentition with a retained right primary mandibular lateral incisor, poor oral hygiene and deep carious lesions in all primary teeth. Hypomineralisation and simple caries were evident in all of the first permanent molars (figure 2). Soft tissue was normal except for generalised moderate gingival inflammation. An assessment of dental occlusion revealed that the patient had posterior unilateral crossbite, severe open bite and increased overjet with high palatal vault due to continuous thumb sucking. The patient’s parents reported that he sucked his thumb most of the day.

Figure 1.

The patient’s craniofacial manifestations (convex profile, bulbous nasal tip, increased lower facial height, retrognathic posture of the mandible, hooded eyelids and protruding ears).

Figure 2.

Oral findings for the patient with 22q11.2DS that show severe open bite, left unilateral posterior crossbite, poor oral hygiene and deep carious lesions.

Investigations

Radiographic examination revealed ectopic eruption of the permanent mandibular right lateral incisor and the permanent mandibular left first premolar and several decayed teeth associated with periapical lesions (figure 3).

Figure 3.

Radiographic examination of the patient revealed ectopic eruption of the permanent mandibular right lateral incisor and the permanent mandibular left first premolar and several decayed teeth associated with periapical lesions.

Treatment

Complete mouth rehabilitation under general anaesthesia was planned for the patient due to his significant limitations in intellectual function and adaptive behaviour as well as the extent of treatment. The treatment consisted of oral prophylaxis, fluoride application, pulp therapy, stainless steel crowns for badly decayed primary teeth, extraction of hopeless teeth and restoration of carious and hypomineralised teeth. A fixed palatal crib was used as a habit breaking appliance for 6–8 months to encourage the patient to stop thumb sucking and improve his overbite and overjet.

Because of the patient’s condition, his physicians were consulted regarding his medical history to ensure that precautions were taken to avoid any possible complications during his dental treatment. His physicians suggested a calcium blood test and complete blood count 24 hours before the operation. In addition, prophylactic antibiotics were prescribed for the patient due to his compromised immune system, which might render him susceptible to transient bacteraemia following the invasive dental rehabilitation. The patient was subjected to careful perioperative and postoperative monitoring of various metrics, including ionised calcium, oxygen saturation and heart rate. We also considered using small intubation equipment, lubricant and/or gentle manipulation for the patient. The patient’s parents understood and agreed to the planned treatment, and informed consent was obtained. Meticulous oral hygiene instructions and diet counselling were clearly provided to the parents.

Outcome and follow-up

The patient was discharged on the day of treatment and advised to undergo regular follow-up and future orthodontic treatment. However, in the 3 months’ recall visit, good oral hygiene was achieved and thumb sucking was discontinued. In addition, periapical radiographs showed normal periodontium (figure 4).

Figure 4.

Postoperative clinical and radiographic examination of the patient during a 3-month recall visit.

Discussion

22q11.2DS is a multisystem syndrome with wide variability in its severity and extent of expression in affected patients.⁹ Moreover, most disorders associated with this syndrome may appear perplexing because these disorders are primarily diagnosed and characterised by physicians who are focused on their particular field of interest.¹⁰ However, patients with 22q11.2DS usually express mild facial dysmorphism.¹¹ The recognition of such features could help with the early diagnosis of this syndrome. Improvements in palliative cardiac repair and medical care have led to decreased infant mortality from 22q11.2DS and have increased the affected population.¹² Dental practitioners are likely to see such patients; therefore, they should be knowledgeable and capable of making a full assessment and providing comprehensive dental management.

The literature on dental manifestations of 22q11.2DS is rather sparse. However, our review of relevant literature indicated that dental manifestations are not uncommon. A high prevalence of tooth agenesis has been reported, with the mandibular incisors, maxillary lateral incisors and maxillary second premolars as the main teeth that are affected,^{8 13–15} although da Silva Dalben et al¹⁶ reported no difference in the incidence of tooth agenesis in affected and control groups.¹⁶ A solitary median maxillary central incisor was reported in a single case with 22q11.2DS by Yang et al.¹⁷ Delayed tooth formation and eruption has also been reported.¹⁸ Dental age, sequence of eruption, developmental defects and space analysis should be periodically evaluated clinically and radiographically in patients with 22q11.2DS.

Defects in the quality and quantity of enamel are also common findings, with a predominance of hypomineralisation, particularly in permanent teeth.¹⁵ In the presented case, poor oral hygiene and enamel disturbance led to an elevated risk of dental caries and gingival inflammation. However, in disabled patients, increased prevalences of caries and gingivitis are essentially attributable to poor oral hygiene. Health providers and family members should be motivated by and informed about these oral health challenges, and access to dental care should be ensured. Routine dental visits will also help maintain and improve the oral health of patients with 22q11.2DS.¹⁹

Patients with 22q11.2DS usually exhibit retrusion of the lower third of the face (class II malocclusion) and anterior open bite.^{8 13} The presented patient demonstrated a severe open bite, a lack of vertical overbite and a unilateral posterior crossbite. These manifestations were caused by non-nutritive thumb sucking and tongue thrusting. A palatal crib was fabricated and delivered to the patient. The parents and child were informed about possible initial side effects that might occur, especially with respect to eating, speaking and sleeping; these effects typically subside after a few days. Patient counselling, reminder therapy, a reward system and adjunctive therapy should be utilised at an early age after evaluation of a child’s psychology to prevent complications from a sucking habit. In our case, orthodontic consultation regarding the posterior crossbite was obtained.

Other dental-related disorders observed in patients with 22q11.2DS include submucous cleft palate, which, in combination with velopharyngeal insufficiency, can cause speech impairment.⁸ A multidisciplinary team that includes a speech therapist should contribute to the management of affected individuals.

Complications such as seizures and difficult intubation may arise more frequently in patients with 22q11.2DS than in typical patients when general anaesthesia is administered.¹⁰ Passariello and Perkins reported a case involving unexpected postoperative tachycardia after dental extractions.²⁰ Careful perioperative and postoperative monitoring of ionised calcium, oxygen levels and heart rate as well as the use of smaller intubation equipment should be regularly practised in patients with 22q11.2DS.¹⁰ In our study, dental rehabilitation under general anaesthesia was accomplished without any complications.

Patients with 22q11.2DS show remarkable phenotypic variability; as a result, diagnoses of this disease can be easily missed. However, mild facial dysmorphism and common dental manifestations are typically noticeable in patients with this syndrome. Therefore, paediatric and general dentists may have the opportunity to diagnose and refer such cases to appropriate specialists. Impaired dental structures and systemic disorders associated with 22q11.2DS could contribute to poor oral health. Thus, dental practitioners should consider early management to provide preventive and therapeutic interventions and thereby achieve optimum oral health. In addition, cooperation among and experience with different specialties is mandatory to improve quality of life for patients with 22q11.2DS.

Patient’s perspective.

‘I didn’t know the implication of the prolonged thumb sucking on my son. I just realised the importance of visiting paediatric dentists to help sick kids improve their oral hygiene as well as diagnose and treat any existing disease. If this had been done, my son would not have had to go through all those problems. However, I am very pleased with all the care he received in the hospital. I would like to thank all the medical staff for their efforts.’ (Translated from Arabic to English by the first author).

Learning points.

• 22q11.2 deletion syndrome (22q11.2DS) is not uncommon, and the number of patients with this syndrome is increasing. Therefore, dental practitioners should have the ability to identify and refer such patients to appropriate specialists.

• Patients with 22q11.2DS have an increased risk of dental caries and gingival inflammation. Therefore, preventive strategies and therapeutic interventions should be planned early for such patients.

• An open growth pattern is a common feature in patients with 22q11.2DS, as well as intellectual disability. In these patients, open bite should be prevented at an early age by eradicating the parafunctional habit (thumb sucking, tongue interposition and so on) as soon as possible.