NORD gratefully acknowledges Yoshiyuki Mochida, DDS, PhD, Clinical Associate Professor, Boston University, Henry M. Goldman School of Dental Medicine, Department of Molecular and Cell Biology, for assistance in the preparation of this report.
Amelogenesis imperfecta (AI) refers to a group of rare, inherited disorders characterized by abnormal enamel formation. 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 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.
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 or 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 clearly less dense (hypomineralized) and pitted.
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) is 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 for 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 is able to 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.
AI affects 1 of 14,000 to 16,000 children in the United States. Of this number, about 40% have the hypocalcified dominant type. The autosomal dominant and recessive forms of the disorder affect males and females in equal numbers. The X-linked dominant type of the disorder affects twice as many males as females. The X-linked recessive type affects only males.
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.
Full crown restorations and a type of denture that caps defective teeth and corrects open bite are excellent treatments for this disorder. Desensitizing toothpaste can prevent painful sensitivity to heat and cold. Good oral hygiene is important. Genetic counseling is recommending for families of children with AI.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Hu JC-C, Simmer JP. Amelogenesis Imperfecta . In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:
Gorlin RJ, Cohen MMJr, Levin LS. eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990:864-66.
Wright JT. Amelogenesis imperfecta: genotype-phenotype studies in 71 families. Cells Tissues Organs. 2011;194(2-4):279-83.
Ayers KM, Drummond BK, Harding WJ, et al. Amelogenesis imperfecta-multidsciplinary management from erupton to adulthood. Review and case report. NN Z Dental J. 2004;100:101-04.
Weerheijm KL, Mejare I. Molar incisor hypomineralization: a questionnaire inventory of its occurrence in member coutries of the European Academy of Paediatric Dentistry (EAPD).
Int J Paediatr Dent. 2003;13:411-16.
Hu JC, Yamakoshi Y. Enamelin and autosomal-dominant amelogenesis imperfecta. Crit Rev Oral Biol Med. 2003;14:387-98.
Wright JT. Hart PS, Aldred MJ, et al. relationship of phenotype and gentypein X-linked amelogenesis imperfecta. Connect Tissue Res. 2003;44 Suppl 1:47-51.
Aldred MJ, Savarirayan R Crawford PJ. Amelogenesis imperfecta: a classification and catlogue for the 21st century. Oral Dis. 2003;9:19-23.
Hart PS, Hart TC, Simmer JP, et al. A nomenclature for X-linked amelogenesis imperfecta Arch Oral Biol. 2002;47:255-60.
McKusick VA, ed. Online Mendelian inheritance in man (OMIM). The John Hopkins University. Amelogenesis Imperfecta 1, Hypoplastic Type; AIE1. Entry Number; 301200. Last Edit Date; 9/23/2016. https://www.omim.org/entry/301200?search=301200&highlight=301200 Accessed Nov 9, 2020. (See also OMIM 301201; 104530; 104500; 204650; 616270; 204690; 616221; 617297)
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The John Hopkins University. Amelogenesis Imperfecta, Hypomaturation Type; AI IIA1. Entry Number; 204700. Last Edit Date; 04/01/2015. https://omim.org/entry/204700 Accessed Nov 9, 2020. (See also OMIM 612529; 613211; 614832; 615887; 617217)
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The John Hopkins University. Amelogenesis Imperfecta, Hypocalcification Type; AI IIIA. Entry Number; 130900. Last Edit Date; 04/11/2019. https://omim.org/entry/130900 Accessed Nov 9, 2020. (See also OMIM 617607; 618386)
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The John Hopkins University. Amelogenesis Imperfecta, Hypomaturation-Hypoplasia Type with Taurodontism; AIHHT. Entry Number; 104510. Last Edit Date; 04/25/2008. https://www.omim.org/entry/104510 Accessed Nov 9, 2020.
Kapner M. Amelogenesis imperfecta. MedlinePlus. Medical Encylcopedia. Review Date 2/06/2020. https://medlineplus.gov/ency/article/001578.htm Accessed Nov 10, 2020.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100