Timeline of Amelogenesis Imperfecta Management

Abstract

Amelogenesis imperfecta is a heterogeneous group of >100 different rare diseases. Affected individuals and families are facing diagnostic uncertainty and wandering and a therapeutic odyssey. Continuous multidisciplinary management from childhood to adulthood is essential, emphasizing the critical role of health care professionals. Clinical and genetic diagnoses and treatment options are still a matter of discussion and debate. This article, written by the European Reference Network ERN CRANIO Orodental group, describes the roles of the involved health professionals and provides guidelines and timelines for critical intervention periods to improve the management of this condition.

Amelogenesis imperfecta (AI) is a heterogeneous group of >100 different entities among the 7,000 rare genetic diseases identified.^1–4 Its prevalence was estimated to range from 1/700 to 1/14,000 individuals,¹ but these figures do not reflect the diversity of AI nor the recent understanding of their genetic etiology. The average time of diagnostic wandering in rare diseases is nowadays estimated to range from 4 to 5 years. However, disorders affecting the oral cavity, such as AI, are often poorly recognized and diagnosed. AI affects enamel development, a process known as amelogenesis, in both primary and permanent dentitions or in permanent dentition only.^5,6 These diseases can exist as an isolated trait, ie, with clinical manifestations limited to the oral cavity or associated with other symptoms in syndromes.^1,3,6 Individuals with AI may experience various dental issues, including tooth and enamel dysplasia, discoloration and structure post-eruptive breakdown, dentin sensitivity, and progressive loss of occlusal vertical dimension (OVD). They may also be more susceptible to cavities, chronic gingivitis or gingival hyperplasia, and malocclusions like anterior open bite.^1–3 Other dental/jaw anomalies may include missing teeth, taurodontism, pathologic crown and root resorption, delayed tooth eruption, and transverse discrepancies in the maxillary dental arch.^1,4,7 In addition, there is a higher tendency for impacted permanent teeth and follicular cysts, as seen in enamel renal syndrome.⁸

Children with AI require long-term management and follow-up to improve and maintain good oral hygiene and overall oral health.² Simple tasks such as brushing may be really challenging due to hypersensitivity and pain. Teeth desensitization will be a long-term achievement. Orthodontic treatment will often be necessary to address functional and esthetic concerns.

Early diagnosis, tailored therapy, and an appropriate follow-up are critical for favorable outcomes. The severity of AI, patient age, level of oral hygiene, amount and quality of the remaining tooth structure, the condition of the periodontal tissues, and orthodontic factors will influence prosthodontic treatment. The treatment must be tailored to the patient’s needs. The goals of AI treatment are to enhance oral health, preserve the dental structures, restore function, and normalize the smile esthetics.⁹ Patients and parents need to be guided through this long-term course of treatment, including the adoption of coping strategies.

AI imposes significant psychological and financial burdens on individuals and families, including concerns about bullying,^10,11 high treatment costs, frequent dental visits, and increased emergency care needs. AI negatively impacts daily quality of life through esthetic concerns, functional problems, pain, and hypersensitivity.¹² In addition, limited access to specialized care, unclear referral pathways, and the distance to expertise centers further complicate its management.¹³ The absence of established referral systems or clear routes to specialist care for individuals with AI¹⁴ further disrupts patient care pathways, leaving general dental practitioners and patients without crucial support for accurate diagnosis, treatment planning, and comprehensive care.¹³

This article outlines a structured management timeline for AI patients, offering recommendations for timely specialist referrals and guidance on critical intervention periods to optimize care.

EUROPEAN REFERENCE NETWORKS: SPECIALIZED CENTERS FOR RARE ORAL DISEASES

Specialized centers for rare oral diseases, recognized and launched in 2017 by the European Commission, form part of the European Reference Networks (ERN); see ERN CRANIO (https://www.ern-cranio.eu).¹⁵ These cross-border networks connect European hospital centers of expertise to address complex and rare conditions, guided by the principles of Share, Care, and Cure.

In France, through successive governmental rare diseases national health plans (PNMR1-3, number 4 has recently been launched), a similar organization of rare disease centers focused on rare oral and dental diseases (https://www.o-rares.com) gathered under a Filière TETECOU umbrella (https://www.tete-cou.fr) has existed since 2016. In the United Kingdom, a clinical network for children with AI was also established.¹⁶

In the Netherlands and Denmark, treatment of rare dental and orofacial diseases (including AI) has been centralized as well.

The main goal of these expertise networks is to improve patient care through:

• Access to precision clinical and genetic diagnosis of developmental dental anomalies such as AI,^3,17,18

• Reduction of diagnostic wandering,

• Implementation of local, multidisciplinary referral services combining rare disease expertise. The centers work in coordination and collaboration with nonspecialized health care professionals, in both hospital and outpatient settings supported by teleconsultation and tele-expertise.

The networks also collaborate on writing clinical guidelines,¹⁹ offering undergraduate and postgraduate training, disseminating knowledge (https://www.youtube.com/playlist?list=PL0LtsL_Mr0Yzjttyj2-c9CYT9WbKdbi4y), conducting research, proposing innovative approaches and treatments, and engaging with patients’ support groups (https://amelogenesefrance.wixsite.com/amelogenese).

Comprehensive care for patients with AI and their families is based on a multidisciplinary approach. It involves collaboration between the general dentist and specialized centers for rare oral and dental diseases (including expertise in pediatric dentistry, restorative/prosthetic rehabilitation, implantology, periodontology, oral medicine, dentofacial orthopedics, and oral surgery…), the attending physician, and the geneticist. Cases may also be reviewed in multidisciplinary team meetings when necessary. The ERN provides the CPMS 2.0 tool, a Clinical Patient Management System IT Platform for Clinical Consultations between ERN Members (https://cpms.ern-net.eu/).

Systematized Follow-Up for Amelogenesis Imperfecta: A Multidisciplinary Approach

The initial consultation is critical to establish a proper diagnosis and involves gathering all relevant information, including comprehensive medical and dental history records and full oral, clinical, and radiological documentation. It is essential to establish a precision diagnosis based on quality-of-life assessment, scan imaging, 3D photos, and DNA tests. The management of AI typically involves 3 main specialties: pediatric dentistry, dentofacial orthopedics, and prosthetic dentistry (Supplemental Table 1, Supplemental Digital Content 1, http://links.lww.com/SCS/H662). Treatment is often long and complex, proceeding through phases of prevention, restorative dentistry, follow-up, and maintenance (Fig. 1). The collected information may serve as baseline data for the implementation of a European registry to support improved diagnosis and management of AI (https://www.ern-cranio.eu/ern-cranio-registry).

FIGURE 1.

Flowchart of the care pathway for a patient with amelogenesis imperfecta. Inspired by Radboud University Medical Center, the Netherlands

Pediatric Dentistry: Early Diagnosis and Preventive Care for AI

The foundation of pediatric dental care is an early diagnosis accompanied by preventive measures implemented as soon as possible. In case amelogenesis imperfecta can be recognized in the primary dentition, initial diagnosis and follow-up should begin at the moment of emergence of the first tooth, typically around 6 months of age, with a clinical examination conducted by a general dental practitioner or specialized dentist. This approach aims to prevent issues and preserve tooth structure as much as possible from the earliest stages. Even when restorative care for primary teeth is not required, early visits are essential, familiarizing the child with the practitioner, dental environment, and procedures.

Diagnosis can be confirmed by a specialist in rare diseases and/or a geneticist from the age of 2. Genetic testing should be considered especially in cases where AI is suspected to be associated with a syndrome.

An assessment of caries risk is recommended to establish suitable preventive measures. Educating families on oral hygiene and dietary habits is vital. Even without restorative needs, application of high-fluoride varnish is recommended for caries prevention and enamel remineralization facilitation. Fluorides are also beneficial for desensitization purposes.

Treatment solutions should consider the child’s age, cooperation level, and specific dental conditions. Glass ionomer cement can be used as a provisional treatment, particularly for very young children and/or those with poor cooperation. However, when more definitive care is feasible, composite resin restorations are preferred for their durability. Given the delayed transition from primary to permanent dentition and the prevalence of dental anomalies, an orthopantomogram is crucial for the early identification of these conditions. In this phase, the pediatric dentist plays an essential role in identifying potential anomalies, that may require referral for an orthodontic consultation. In addition, some patients may exhibit abnormal oral habits, requiring evaluation and treatment by a speech therapist to address functional concerns.

Guiding the child and implementing behavior management is key for these children in need, sometimes of extensive treatments.

Dentofacial Orthopedics: Orthodontic Treatment for AI Patients

Orthodontic treatment for patients with AI aims to facilitate oral hygiene, improve tooth alignment, restore or maintain masticatory function, and prevent complications such as open bites or posterior crossbites.²⁰ Patient and parent expectations often include esthetic improvements, and realistic goal setting is essential. Orthodontic treatment in AI presents unique challenges, including bracket bonding failure due to compromised enamel quality, longer treatment durations and higher complication rates, as well as increased sensitivity to pain.

Treatment is often conducted in phases. An examination around 6 to 8 years of age is recommended for early identification of anomalies. Initial efforts address tooth impaction, eruption difficulties, and space management issues, sometimes through serial extractions. Growth-modification methods, such as block appliances or reverse headgear, may be indicated in younger patients. Many alternatives are available nowadays. In cases of maxillary constriction, upper jaw expansion may also be required. The later stages involve aligning the dental arches.

A multidisciplinary team is always necessary. Backward planning, in collaboration with the specialized dentist, is essential before the start of the orthodontic treatment. For example, in some cases, alignment of the teeth may need to leave open or redistribute spaces between teeth to allow for indirect composite crowns or other prosthetic solutions to provide a complete mouth rehabilitation with an esthetic smile. This also helps to reduce severe hypersensitivity and prevent the preparation of the tooth surfaces. Restauration of contact points to establish proper distances between roots and re-establish a correct OVD; also extractions or intrusion of second molars may be required.²¹

After the active treatment phase, a retention phase typically begins. Retention is managed using fixed retainers (bonded wires) and removable night guards to maintain the achieved treatment outcomes.

In adulthood, skeletal discrepancies must be re-evaluated, and surgical correction may be considered if necessary.^22–24 More recent approaches, such as aligners,²⁵ are increasingly viable alternatives for orthodontic care in individuals with AI. Aligners can offer greater comfort and are often better accepted by patients with oral hypersensitivity. However, the retentive aspect must be carefully considered due to the reduction in the crown height and absence of undercuts.²⁵ Close monitoring, including scheduling multiple consecutive appointments, is crucial for maintaining optimal oral hygiene and following up treatment progress.

Prosthetic Dentistry: Restoring Function and Esthetics in AI

At pediatric age, between 2 years of age and the onset of mixed dentition, in cases of severe decay or missing enamel, and to prevent or restore loss of OVD, preformed pediatric crowns (PPCs) are indicated. Metal (Ni-Cr) PPCs can be used on primary molars in the absence of esthetic requirements. Zirconia PPCs can be used on all primary teeth in cases of severe enamel defects and esthetic complaints. New esthetic crowns are being developed. Furthermore, a space maintainer or a pediatric prosthesis must compensate for the absence of primary teeth. These early treatment stages are often performed under general anesthesia or using various conscious sedation methods.

During the periods of mixed dentition (6–8-year-old), adolescent dentition (eruption of permanent canines and premolars), and young permanent dentition (eruption of second permanent molars), the follow-up is multidisciplinary. It should focus on prevention, preserving the OVD, reducing tooth sensitivity, and improving esthetics. The risk of pulpal exposure or irreversible pulpal inflammation is increased in the case of coronal preparation, due to the large pulp volume.

From mixed to permanent dentition (transition stage), dental rehabilitation is complex. Permanent teeth have eruption sequences that extend over a period of 6 years, and definitive treatment is more likely to be considered only when growth is complete. These treatments also need to be compatible with orthodontic treatment.

During adolescence and adulthood, indirect prosthetic restorations are an option when preventive methods or direct restorations (composites or glass ionomers) fail to meet clinical or psychological needs.

However, the nature of the restoration is highly dependent on the type and severity of AI. Direct composite restorations involving the bonding of materials to enamel are recommended for anterior teeth for esthetic reasons. They can also be used to restore permanent premolars and molars temporarily. The durability of these restorations is significantly poorer in cases of hypomature/hypomineralized AI compared with hypoplastic AI. The longevity of composite restorations is therefore highly dependent on the quantity and quality of the enamel.

Depending on the type of AI, direct composite restorations should be considered temporary until a definitive restoration can be achieved at the completion of growth. However, indirect bonded composite or ceramic restorations (veneers, crowns, onlays/inlays) can offer better longevity. Nowadays, ceramic crown therapy in adolescents and young adults with severe forms of AI shows excellent survival and success rates and longevity with few adverse events²⁶ as well as triggers cost reduction with few complications and reduced need for dental care during adolescence²⁷ and therefore pleads for earlier intervention.

Frequent appointments and recalls are necessary to assess gingival and periodontal status, ensure optimal oral hygiene, and prevent tooth destruction due to carious lesions and periodontal disease, ensuring optimal periodontal health.

DISCUSSION

Dental care for AI patients is challenging and requires a thorough, multidisciplinary approach based on an accurate diagnosis.²⁸ Genetic diagnosis may exclude or confirm a syndromic condition such as Enamel Renal Syndrome or Jalili syndrome, among many others.^3,8 Early diagnosis and substantial, intensive treatment over several sessions are required, particularly for individuals diagnosed at a young age.¹³ In addition, patients require psychological support, especially during puberty, to help them develop a coping mechanism for managing their condition.²⁹ Several variables, including clinical complaints, psychological issues, and restorative difficulties, influence the diagnosis and therapy of AI.¹³ Parents also recognize the need for ongoing care and the unpredictability of upcoming therapies. They are aware that untreated dental appearance can make the child more vulnerable to social stigmatization, complicating the management of the condition.¹⁰

The patient’s age will also affect the course of treatment and follow-up. Early diagnosis is crucial for preserving tooth structures and occlusal relationships. The therapy involves restorative procedures and preventive care, including stainless-steel crowns on the posterior teeth during the primary dentition. Long-term temporary treatment is necessary for the mixed dentition to address hypersensitivity, tooth structure loss, preservation of OVD and esthetics preservation. The treatment plan typically focuses on orthodontic and prosthetic rehabilitation. Early dental treatment provides optimal conditions for the eruption of permanent teeth and normal growth of facial bones.²

The treatment goals in the permanent dentition are to restore OVD, function, and esthetics while also reducing tooth sensitivity. At this point, a multidisciplinary strategy including orthodontic, periodontal, restorative, endodontic, and prosthodontic therapy is recommended.² Placing definitive prosthetic restorations such as veneers or crowns is the advised long-term treatment strategy for individuals with AI since early adolescence.^9,13 In addition, adolescent prosthetic rehabilitation has shown to be more economical than delaying final treatment.¹³ Optimal periodontal health and proper oral hygiene should also be considered to avoid the destruction of erupted teeth in both dentitions by carious lesions and periodontal disease.²⁸

CONCLUSIONS

Dental care for amelogenesis imperfecta patients requires a comprehensive and individualized, personalized approach, with multidisciplinary collaboration being essential for optimal outcomes. Early diagnosis, regular monitoring, follow-up, frequent appointments, and the use of appropriate orthodontic appliances are critical for achieving success. Timely referral to specialized care providers and collaboration among oral biologists, pediatric dentists, orthodontists, prosthodontists, periodontists, speech therapists, caregivers, and other professionals ensure the best possible outcomes for these patients. These efforts also significantly enhance the quality of life for individuals with amelogenesis imperfecta, addressing their functional, esthetical, and psychological needs. Due to the rarity of amelogenesis imperfecta and differences in diagnostic criteria, obtaining precise prevalence figures for each European country is challenging. Further epidemiological studies are necessary to determine more accurate country-specific data. Setting up an ERN registry for amelogenesis imperfecta at the European level will allow addressing the following issues: prevalence of amelogenesis imperfecta as a whole and/or as individual separate rare diseases on the basis of their genetic etiology and isolated or syndromic nature, treatment needs and costs as well as comparison of strategic management principles, policies, and practices, including financial burden in the different participating countries. These data will be indispensable to deliver informed guidelines and ensure equity of management within European countries.