Amelogenesis imperfecta (AI) refers to a group of rare, inherited disorders characterized by abnormal incomplete enamel formation or calcification of the enamel and characterized by loss of enamel, poor esthetics, hypersensitivity associated with the abnormal dental eruption, congenital absence of teeth, anterior open occlusal relationship, calcification of the pulp, dentin dysplasia, crown, and root resorption, hypercementosis, malformation in roots, and taurodontism [rx, rx]. The term is typically restricted to those disorders of enamel development not associated with other abnormalities of the body.
Clinical researchers usually classify AI into four main types of which 17 subtypes are recognized. The main types are based on clinical appearance, radiographic appearance, and enamel thickness, and the subtypes are based on the mode of inheritance and gene mutation. The main types are: hypoplastic (type I); hypomaturation (type II); hypocalcified (type III); and hypomaturation/hypoplasia/taurodontism (type IV). AI may be inherited as an X-linked, autosomal dominant, or autosomal recessive genetic trait, depending on the subtype.
Types
The most widely accepted classification of AI includes four main types:
- hypoplastic (type I),
- hypomaturation (type II),
- hypo calcification (type III), and
- hypomaturation‐hypoplasia with taurodontism (type IV)
Symptoms
AI is characterized by defective or missing tooth enamel.
Secondary effects of this disorder may be cracked tooth, early tooth decay, and/or loss, in addition to susceptibility to multiple diseases of the tissues surrounding teeth (periodontal tissues) such as gums, cementum, ligaments, and alveolar bones in which the tooth root rests. Teeth are also sensitive to both hot and cold exposures, and sometimes both. This sensitivity can be due to the exposed sensitive dentin layer which is usually entirely protected by the enamel layer on top. The dental pulp in the root canal is where all of the tooth nerves are located, and the exposed sensitive dentin typically leads to continuous severe pain.
The psychological trauma of patients with AI cannot be overlooked. Patients with AI have unsightly teeth that are discolored or spaced. Moreover, some patients also suffer from what’s called an open bite (the upper and lower jaws do not align properly), which results in an unpleasant appearance of the teeth. With continuous restorative, orthodontic and periodontal restoration, however, the teeth can end up looking normal and remain functional throughout the life of the individual. These dental treatments are expensive and require huge dedication. Patients who cannot afford these treatments sometimes have their teeth pulled, which adds more to their psychological trauma.
Type I hypoplastic AI is characterized by small to normal tops (crowns) of the teeth, upper and lower teeth that do not meet showing a poor bite, and teeth that vary in color from off-white to yellow-brown. The enamel thickness varies from thin and smooth to normal, with grooves, lines, and/or pits.
Type II hypomaturation AI is commonly associated with an open bite and creamy white to yellow-brown roughly surfaced teeth that may be tender and sore. The enamel is generally normal in thickness but tends to be chipped away or scraped.
Type III hypocalcified AI is seen in patients with an open bite and creamy white to yellow-brown rough enamel-surfaced teeth that may be tender and sore. These teeth usually carry substantial precipitates of stony material from the fluids of the mouth (calculi). The enamel is generally normal in thickness but tends to be chipped away or scraped.
Type IV hypomaturation/hypoplasia/taurodontism AI usually is characterized by smaller than normal teeth, the color of which may range from white to yellow-brown, and teeth that appear to be mottled or spotted. The enamel is thinner than normal with areas that are less dense (hypo mineralized) and pitted.
Causes
Just as the classification of AI is complex, so too is the contribution of genetics to these disorders. Changes (mutations) in specific genes have been identified as the cause of 19 subtypes of AI. The causal gene and mode of inheritance for these subtypes based on the OMIM (Online Mendelian Inheritance in Man) are listed below:
Type I hypoplastic AI
- Type IA: autosomal dominant inheritance, LAMB3 mutation
- Type IB: autosomal dominant inheritance, ENAM mutation
- Type IC: autosomal recessive inheritance, ENAM mutation
- Type IE: X-linked dominant inheritance, AMELX mutation
- Type IE, X-linked 2: X-linked inheritance, gene unknown
- Type IF: autosomal recessive inheritance, AMBN mutation
- Type IG: autosomal recessive inheritance, FAM20A mutation
- Type IH: autosomal recessive inheritance, ITGB6 mutation
- Type IJ: autosomal recessive inheritance, ACPT mutation
Type II hypomaturation AI
- Type IIA1: autosomal recessive inheritance, KLK4 mutation
- Type IIA2: autosomal recessive inheritance, MMP20 mutation
- Type IIA3: autosomal recessive inheritance, WDR72 mutation
- Type IIA4: autosomal recessive inheritance, C4orf26 mutation
- Type IIA5: autosomal recessive inheritance, SLC24A4 mutation
- Type IIA6: autosomal recessive inheritance, GPR68 mutation
Type III hypocalcified AI
- Type IIIA: autosomal dominant inheritance, FAM83H mutation
- Type IIIB: autosomal dominant inheritance, AMTN mutation
- Type IIIC: autosomal recessive inheritance, RELT mutation
Type IV hypomaturation/hypoplasia/taurodontism AI
- Type IV: autosomal dominant inheritance, DLX3 mutation
Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier of the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
In some individuals, the disorder is due to a spontaneous (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.
X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have an altered gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an altered gene he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
If a male with an X-linked disorder can reproduce, he will pass the altered gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
X-linked dominant disorders are caused by an abnormal gene on the X chromosome and occur mostly in females. Females with these rare conditions are affected when they have an X chromosome with the gene for a particular disease. Males with an abnormal gene for an X-linked dominant disorder are more severely affected than females and often do not survive.
Mutations in the AMELX, ENAM, MMP20 and FAM83H genes can cause amelogenesis imperfecta. The AMEX, ENAM, and MMP20 genes provide instructions for making proteins that are essential for normal tooth development. Most of these proteins are involved in the formation of enamel, which is the hard, calcium-rich material that forms the protective outer layer of each tooth. Although the function of the protein produced from the FAM83H gene is unknown, it is also believed to be involved in the formation of enamel. Mutations in any of these genes result in altered protein structure or prevent the production of any protein. As a result, tooth enamel is abnormally thin or soft and may have a yellow or brown color. Teeth with defective enamel are weak and easily damaged.
Mutations in the genes described above account for only about half of all cases of the condition, with FAM83H gene mutations causing the majority of these cases. In the remaining cases, the genetic cause has not been identified. Researchers are working to find mutations in other genes that are involved in this disorder.
Diagnosis
Diagnosis of AI is usually made by visual examination, family history and X-ray examination at the time teeth erupt. The dentist may use a simple hand instrument to distinguish the different types of AI. By one to two years of age, the diagnosis can be made.
Treatment
Full crown restorations and a type of denture that caps defective teeth and corrects open bites are excellent treatments for this disorder. Desensitizing toothpaste can prevent painful sensitivity to heat and cold. Good oral hygiene is important. Genetic counseling is recommended for families of children with AI.
Preventive and restorative dental care is very important as well as considerations for esthetic issues since the crown is yellow from exposure to dentin due to enamel loss.[rx] The main objectives of treatment are pain relief, preserving the patient’s remaining dentition, and treating and preserving the patient’s occlusal vertical height.[rx]
Many factors are to be considered to decide on treatment options such as the classification and severity of AI, the patient’s social history, clinical findings, etc. There are many classifications of AI but the general management of this condition is similar.
Full-coverage crowns are sometimes being used to compensate for the abraded enamel in adults, tackling the sensitivity the patient experiences. Usually, stainless steel crowns are used in children which may be replaced by porcelain once they reach adulthood.[rx] These aid with maintaining occlusal vertical dimension.
Aesthetics may be addressed via placement of composite or porcelain veneers, depending on patient factors e.g. age. If the patient has primary or mixed dentition, lab-made composite veneers may be provided temporarily, to be replaced by permanent porcelain veneers once the patient has stabilized permanent dentition. The patient’s oral hygiene and diet should be controlled as well as they play a factor in the success of retaining future restorations.
In the worst-case scenario, the teeth may have to be extracted and implants or dentures are required. Loss of nerves in the affected teeth may occur.
References
