Amelogenesis imperfecta

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Amelogenesis imperfecta is a group of disorders of tooth development. In people with this condition, tooth enamel does not form properly. Tooth enamel is the hard, white material that is mainly made of mineral crystals and forms the protective outer layer of each tooth. People with amelogenesis imperfecta may have teeth that appear (erupt) later than normal, and their teeth may be unusually small, discolored, pitted, or grooved. Affected individuals can also have misalignment of the top and bottom teeth (malocclusion). Because of these teeth problems, people with amelogenesis imperfecta often have difficulty eating, sensitivity to certain foods and drinks, and pain when brushing their teeth. Their teeth are also prone to rapid wear, frequent cavities, and breakage. Other dental abnormalities are also possible. These problems can affect both primary (baby) teeth and permanent (adult) teeth.

Because amelogenesis imperfecta causes changes in a person's appearance, the condition can profoundly affect quality of life and self-esteem if not treated. In some people, the condition can lead to avoidance of social activities, anxiety, and other emotional or psychological issues.

Researchers have described at least four forms of amelogenesis imperfecta: hypoplastic (also referred to as type I), hypomaturation (type II), hypocalcified (type III), and hypomaturation and hypocalcified with taurodontism (type IV). These types are generally distinguished by their specific enamel abnormalities. The hypoplastic type is defined by thin enamel, the hypomaturation type is defined by weak or brittle enamel, and the hypocalcified type is defined by soft enamel. The hypomaturation and hypocalcified with taurodontism type involves weak and soft enamel and teeth that are too large for the size of their roots, which are small (this combination is known as taurodontism). These four types of amelogenesis imperfecta are further divided into subtypes according to their pattern of inheritance and their genetic cause.

Some doctors simplify the classification of amelogenesis imperfecta by grouping structural problems with enamel into one group (quantitative enamel defect) and strength or hardness issues with enamel into a second group (qualitative enamel defect).

Amelogenesis imperfecta can occur without any other signs and symptoms (isolated) or it can occur as part of a syndrome that affects multiple parts of the body (syndromic). A subtype of type I, known as amelogenesis imperfecta type IG, can affect the kidneys and is called enamel-renal syndrome. People with this condition may develop calcium deposits in the kidneys (nephrocalcinosis) later in life.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in more than 20 different genes can cause amelogenesis imperfecta. Variants in the SACK1H, FAM20A, AMELX, and ENAM genes account for over half of all cases. These genes, as well as many other genes that are associated with amelogenesis imperfecta, provide instructions for making proteins that are essential for normal enamel and tooth development.

Variants in the genes that are associated with amelogenesis imperfecta often lead to an altered protein structure or prevent the production of any functional proteins. As a result, tooth enamel does not form normally and may instead be thin, weak, or soft. The abnormal enamel results in teeth that are easily damaged and can become discolored.

Some people with amelogenesis imperfecta do not have a variant in any of the genes that are associated with this condition. In these people, the genetic cause of the condition is unclear. However, enamel defects can occur in combination with dozens of other conditions.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Amelogenesis imperfecta can have different inheritance patterns depending on the specific gene that is altered.

When amelogenesis imperfecta is caused by variants in the SACK1H gene, it is inherited in an autosomal dominant pattern. This type of inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.

When this condition is caused by variants in the FAM20A gene, it is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

When this condition is caused by variants in the ENAM gene, it can be inherited in either an autosomal dominant or an autosomal recessive pattern.

When amelogenesis imperfecta is caused by variants in the AMELX gene, it is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome), one altered copy of the gene may or may not cause the features of the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In most cases, males with amelogenesis imperfecta caused by AMELX gene variants experience more severe dental abnormalities than females with similar variants.

In some cases, amelogenesis imperfecta can result from new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals have no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of amelogenesis imperfecta varies widely depending on the population, from 1 in 700 people in northern Sweden to 1 in 14,000 people in the United States. Type I is the most common form, accounting for about half of all cases.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of dental color · Very frequent (99-80%)

A developmental defect of tooth color.

Yellow-brown discoloration of the teeth · Very frequent (99-80%)

Anterior open-bite malocclusion · Frequent (79-30%)

Anterior open bite is a malocclusion characterized by a gap between the anterior teeth (incisors), that is, by a deficiency in the normal vertical overlap between antagonist incisal edges when the posterior teeth are in occlusion.

Enamel hypomineralization · Frequent (79-30%)

A decreased amount of enamel mineralization. Hypomineralized enamel has a brown discoloration and brittle aspect.

Enamel hypoplasia · Frequent (79-30%)

Developmental hypoplasia of the dental enamel.

Fragile teeth · Frequent (79-30%)

A tendency of teeth to fracture as manifested by a history of repeated fracture of the dental enamel without adequate trauma.

Hypocalcification of dental enamel · Frequent (79-30%)

A form of hypomineralization of enamel characterized by reduced calcification.

Hypomature dental enamel · Frequent (79-30%)

A form of hypomineralization of enamel characterized by a chalky appearance of the enamel with orange, brown, or white color.

Other findings in the same source

From: Orphanet

Additional reported features include Impaired mastication (Frequent (79-30%)); Abnormal jaw morphology (Occasional (29-5%)); Abnormality of dentin (Occasional (29-5%)); Abnormality of permanent molar morphology (Occasional (29-5%)); Hypoplasia of teeth (Occasional (29-5%)); Multiple unerupted teeth (Occasional (29-5%)); Taurodontia (Occasional (29-5%)); Widely spaced teeth (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Amelogenesis imperfecta is Dentistry, with a dentist / relevant dental specialist as the relevant type of clinician. Dentist / Relevant dental specialist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which teeth, gum tissues or oral structures are affected?
• What is the purpose of any proposed dental imaging or procedure?
• What oral-care routine is suitable while the problem is being treated?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.