Developmental disorder of enamel

1. Amelogenesis
imperfecta (AI)

2. Amelogenesis imperfecta (AI)
Also known as
• Hereditary enamel dysplasia
• Hereditary brown enamel
• Hereditary brown opalescent teeth

3. Definition -
 “AI encompasses a complicated group of conditions that demonstrate developmental
alterations in structure of the enamel in the absence of a systemic disorder”
 “AI represents a group of conditions, genomic in origin, which affect the structure and
clinical appearance of the enamel of all or nearly all the teeth in a more or less equal
manner, and which may be associated with morphologic or biochemical changes elsewhere
in the body”
Orphanet Journal of Rare Diseases 2007,
2:17

4. Historical background -
 Spokes in 1890, described "brown teeth" with a familial history.
 In 1907 Turner described some cases of hereditary hypoplasia of teeth in five generations
of same family
 A paper by Finn (1938) - distinguishes between brown hypoplasia of the enamel and
hereditary opalescent dentine. He comments, in brown hypoplasia of the enamel there are
no faults in dentine
 Weinmann & associates in 1945 – introduced term “Amelogenesis Imperfecta” – it is an
ectodermal disturbance, mesodermal components are normal

5. Development of normal enamel
 occurs in three stages
1. Formative stage – deposition of organic matrix
2. Calcification stage – matrix is mineralized
3. Maturation stage – crystallites enlarge and mature

6.  Disturbance in Formative stage , Causes - Hypoplastic AI
 Disturbance in Calcification stage, Causes - Hypocalcified AI
 Disturbance in Maturation stage, Causes - Hypomaturative AI

7. Prevalence of occurancce
 Ranges from 1 in 718 to 1 in 14,000, depending on the population studied.
 Hypoplastic AI represents 60 – 73% of all cases
 Hypomaturation AI represents 20 – 40%
 Hypocalcification AI represents 7%

8. Etiology of AI
 Developmental, often inherited disorder, occurs in absence of systemic features and
comprises of diverse phenotypic entities.
 According to Alvares and Souza Freitas, “this alteration is probably inhibitory in nature
and causes atrophy and lack of function of ameloblastic cells, leaving as a result structural
defects on enamel formation”.
 Hypoplastic teeth are a characteristic of Amelogenesis Imperfecta,
 Related to genetic causes, autosomal dominant or recessive genes or X-linked

9. Etiology of AI
 Dental enamel is a highly mineralised tissue with 95% of its volume occupied by, highly organised,
hydroxyapatite crystals.
 Formation of this highly organised and unusual structure is controlled in ameloblasts through
interaction of a number of organic matrix molecules that include - Genes and Phenotypes
1. AMELX (amelogenin)
– X-linked
– Diffuse smooth hypoplastic and hypomaturation
2. ENAM (enamelin)
– AD, AR
– Generalized pitting and thin enamel
3. AMBN (ameloblastin)
– Indication for strong association

10. 4 . Amelotin gene (AMELOTIN 4q13)
5. KLK4 (kallikrein-4)
– hypomaturation
6. DLX3 (genes of craniofacial development)
– Hypoplastic/hypomaturation and taurodontism
7. MMP-20 (enamelysin)
– AR pigmented hypomaturation

11.  AI can be transmitted by an autosomal-dominant, autosomal-recessive, or X-linked mode
of inheritance
 Distribution of AI types - vary among different populations.
 A study in Sweden, 63% of cases were inherited as autosomal-dominant.
 In contrast, in a study in Middle East - AI was found to be autosomal-recessive
 Witkop - hypomaturation amelogenesis imperfecta in two families affected only males -
“X-linked recessive amelogenesis imperfecta,” (because the females were thought to be
unaffected)

12.  Amelogenin gene (AMELX) - tooth-specific gene expressed in pre-ameloblasts,
ameloblasts, and in the epithelial root sheath remnants; a low-expression of amelogenin
mRNAs recently shown in odontoblast
 Mutations in (AMELX) gene cause X-linked amelogenesis imperfecta
 Enamelin (ENAM) gene - tooth-specific gene expressed predominantly by enamel
organ, and, at a low level, in odontoblasts.
 ENAM gene - localized on chromosome 4 (4q13.3) & mutations in enamelin gene
(ENAM) cause autosomal-inherited forms of amelogenesis imperfecta.

13.  Ameloblastin (AMBN) gene expressed at high levels by ameloblasts and at low levels by
odontoblasts and pre-odontoblasts, moderate expression in Hertwig's epithelial root
sheath, and in odontogenic tumors, such as in ameloblastomas.
 AMBN is localized on chromosome 4 at locus 4q21,
 AMBN maps within critical region for autosomal-dominant AI, and is therefore
considered as a candidate gene
 Amelotin gene (AMELOTIN 4q13) - reported by Iwasaki et al., 2005 - play a role in
molecular interaction during amelogenesis

14.  KLK4 gene - located near telomere of chromosome 19 (19q13.3 – 19q13.4)
downstream of KLK2 gene, and is considered a member of human tissue
kallikrein gene family
 KLK4 is expressed by both ameloblasts and odontoblasts.
 Due to abnormal enzymic activity - crystallites of enamel grow to the normal
length, but not completely in thickness

15.  MMP-20 gene codes for a calcium-dependent proteinase member of the matrix
metallopeptidases family (MMPs).
 Apart from ameloblasts, pre-ameloblasts, and odontoblasts, expression of MMP-20 in
human odontogenic tumors and carcinoma cell lines originating from tongue has recently
been described
 Mutation in (MMP-20) gene in region 11q22.3 – q23 - associated with autosomal
recessive pigmented hypomaturation AI

16.  Mutation within human DLX3 gene homeodomain - associated with AI (hypoplastic-
hypomaturation type), with taurodontism (AIHHT).
 Dong et al., 2005, suggest that tricho-dento-osseous syndrome (TDO) and amelogenesis
imperfecta hypoplastic-hypomaturation with taurodontism (AIHHT) are allelic for DLX3
 Chromosome 4q13 region contains at least 3 genes important in enamel development:
enamelin, ameloblastin, and amelotin. Enamelin gene mutations have been identified in
autosomal dominant AI
 An additional locus for autosomal dominant AI - found recently on chromosome 8q24.3.

17.  Inheritance pattern of X-linked disorders dictates male-to-male transmission cannot occur.
 All female offsprings of an affected male - affected.
 Affected females have a 50% probability of passing on trait to the offspring of either sex.
 The most striking feature - different manifestations between affected females and affected
males.

18. Classification of AI

20. Witkop and Sauk (1976) -

23. Clinical features
Hypoplastic AI
 Inadequate deposition of organic matrix,
 Normal mineralization
 Colour varies from brown to yellowish brown
 Radiographic features –
 Enamel is very thin, giving the crowns a tapered appearance
 Lack of contact between teeth
 Contrast with the dentin
 Crowns of teeth tend to be square, devoid of normal mesial & distal contours

24. Hypoplastic generalized pitted
 Autosomal Dominant
 Pinpoint/head pits in rows or columns
 In-between, enamel normal
 Buccal surface more severely affected
 Does not correlate with pattern of
environmental damage

25. Hypoplasic localized pitted
• Autosomal Dominant or Autosomal Recessive (more severe)
• Pinpoint/head pits in rows
• Linear depression or area of hypoplasia
• Middle third of buccal surface
• Incisal or occlusal unaffected
• All teeth or some teeth
• Primary or both dentitions

26. Hypoplastic smooth autosomal dominant
 Thin, hard, glossy
 Like crown preparations, open bite
 Opaque white to brown
 Unerupted exhibit resorption

27. Hypoplastic smooth X- linked dominant
• In Males
• – Thin, hard, glossy
• – Like crown preparations, open bite
• – Opaque white to brown
• In Females
• – Alternating vertical bands of normal and
• abnormal enamel
• – Lyonization

28. Hypoplastic rough autosomal dominant
 Thin, hard, rough
 Tapering of occlusal and incisal surfaces
 Open contact
 Open bite

29. Enamel agenesis autosomal recessive
 No enamel
 Teeth have the shape and color of the dentin,
 A yellow-brown hue
 Open contact points, and crowns taper towards the incisal and occlusal surface.
 The surface of dentin is rough and an anterior open bite is seen frequently.
 Radiographs demonstrate no peripheral enamel overlying the dentin.
 A lack of eruption of many teeth with significant resorption frequently occurs.

30. Hypocalcified AI
 Due to disturbance in mineralization of enamel
 Enamel fractures away from teeth because of its chalky consistency
 Crown have a normal shape and size at eruption
 Yellow or brown colour
 Radiographically –
 No contrast between enamel and dentin
 Dentin may even be denser than enamel
 Enamel looks motheaten because of areas of pitting and lost enamel

31. Hypomaturative AI
 Enamel crystallites remain immature causing enamel to be soft
 Enamel can be pierced by an explorer under firm pressure
 Enamel is of normal thickness, but chips and abrades, but not as fast as in
hypocalcified type
 Resorption of enamel occur on incisal and occlusal surfaces prior to eruption
 Radiographically
 No contrast between enamel and dentin

32. Hypomaturative –snow capped
 X-linked, Autosomal Dominant?
 Zone of white opaque enamel on incisal and
occlusal surface (1/4 to 1/3 of the surface)
 Looks like fluorosis
 Anteriors, premolars/molars
 Both dentitions

33. Hypomaturation – Hypoplastic with Taurodontism (AD)
 Predominant defect – enamel hypomaturation
 Enamel appears – mottled yellow-white to yellow brown
 Pits are seen frequently on buccal surface of teeth
 Radiographically –
 enamel appears similar to dentin
 Large pulp chambers may be seen in single rooted teeth in addition to varying degrees of
taurodontism

34. Hypoplastic - Hypomaturation with Taurodontism (AD)
Predominant defect –
- enamel hypoplasia in which enamel is thin but also hypomature
Radiographically
- Similar to hypomaturation-hypoplastic variant, except decrease in thickness of enamel

35.  In hypoplastic form
 Females show vertical ridging of the enamel, whereas, in males is uniform hypoplasia.
 In hypomaturation form
 Males have teeth of normal size and shape, but with irregular, pigmented mottling.
Females display vertical bands of mottling, often inconspicuous under normal lighting
conditions.
 In both types, females represents Lyonization, where alternating groups of ameloblasts
are under control of either the abnormal or normal gene.

36. Description of clinical features of AI by different
Authors

37.  Schulze and Lenz - First clear descriptions of X-linked hypoplastic AI, recognized
different manifestations in affected males and females
 Witkop - an X-linked recessive hypomaturation form in affected males, showed mottling
of the enamel
 Winter and Brook - “X-linked recessive hypomaturation amelogenesis imperfecta,” and
reported enamel to be of normal thickness and relatively soft, so that the surface could be
penetrated with a sharp probe.
 Severe attrition was a feature, especially on premolars and molars and palatal aspects of
upper anterior teeth of males

38.  Haug and Ferguson described “X-linked recessive hypomaturation amelogenesis
imperfecta” -
Teeth in females - “vertical striations in every crown, consisting of voids and wrinkles
interspersed between areas of normal enamel” & enamel was softer than normal with marked
abrasion, discolored, yellow to brown, with cervical enamel of posterior teeth less involved
than enamel of incisors.

39.  Witkop and Stewart - noted that (in the hypomaturation form) mottled yellow-white
color of permanent teeth, darken with absorption of stains.
 In severely affected boys, enamel of permanent teeth was slightly thinner than normal,
with cervical enamel tending to be better formed
 In girls both primary and permanent teeth showed alternating bands of white opaque, and
normal translucent enamel.
 Escobar et al., suggested - snowcapped teeth as an X-linked trait, & also raised the
possibility of an autosomal dominant form

40. Histopathological examination
 Very thin enamel, voids within enamel & composed of laminations of irregularly arranged
enamel prisms
 Enamel-dentin junction, show some exaggerated scalloping.
 Areas of homogeneous aprismatic enamel or fused indistinct prisms, with “a reduction in
distance between enamel rod incremental lines”
 SEM studies of extracted deciduous teeth,(case of autosomal recessive rough hypoplastic
AI), showed an exposed outer enamel surface, with irregularly shaped globular protrusions

41.  Witkop and Sauk et al., - showed marked defects in enamel were seen in outer half.
 Enamel rod sheaths were lacking and filled with “pigmented debris” or with “eosinophilic-staining
material.”
 McLarty et al.. - irregular spaces running from enamel-dentin junction outward in a male considered to
have X-linked hypomaturation AI.
 Some of these consisted of tube-like structures that ended in a peripheral expansion
Darling - described a zone of “markedly hypocalcified enamel” adjacent to enamel-dentin junction in two
teeth from a female with X-linked hypoplastic AI.
Backman et al.,- an affected male (X-linked recessive hypoplastic) showed marked “demineralization” of
enamel close to enamel-dentin junction, with channels of demineralization extending to enamel surface

42. Differential diagnosis for AI
 Dental fluorosis
 Environmental enamel hypoplasia
 Dentinogenesis imperfecta

43. Management
 Usually involves complete oral rehabilitation by -
- full coverage crowns, direct and indirect veneers, and bonded aesthetic restorations, depending
on condition of individual tooth and age of patient
 Types ID, IE, IG, IIA, IIIA, IIIB, and IVB - variants require full coverage as soon as is
practical
 In patients without sufficient crown lengths - full dentures (overdentures in some cases)

44. References
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Genet. 1962;14:135–8.
3. Sauk JJ, Lyon HW, Witkop CJ. Electron optic microanalysis of two gene products in
enamel of females heterozygous for X-linked hypomaturation amelogenesis imperfecta.
Am J Hum Genet. 1972;24:267–76
4. Darling AI. Some observations on amelogenesis imperfecta and calcification of the dental
enamel. Proc R Sot Med. 1956;49:759–65.

45. 5. Lagerstrom M, Dahl N, Iselius L, Backman B, Pettersson U. Mapping of the gene for X-linked
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mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel
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47. THANK YOU