Developmental disorders

Developmental Disorders

Dr. Ali Yaldrum B.D.S, M.Sc (London)

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Learning Objectives

• Define and use the key terms

• Compare and contrast developmental, hereditary, and congenital disorders

• Provide examples of teratogenic agents and describe how a teratogenic agent may affect morphogenesis.

• Describe the characteristics of developmental, hereditary, and congenital disorders.

• Describe the dental implications and appropriate dental care modifications associated with the disorders discussed.

‘The Basics’

• Developmental disorders

• Hereditary disorders

• Congenital disorders

Developmental disorders

• Occur when there is a disturbance in the development of the body that results in an abnormality.

• "e developmental abnormality can be very severe and cause spontaneous abortion or miscarriage or it can be very minor and cause few, if any, problems.

Hereditary disorders

• Caused by a genetic abnormality that can be passed from generation to generation.

• Many hereditary conditions are not compatible with life and result in a spontaneous abortion or early infant death; others can be very mild and not even noticed.

Congenital disorders

Congenital abnormalities, sometimes called birth defects, are present at or around the time of birth and can be caused by a variety of factors

A congenital abnormality could be hereditary or developmental, as long as it is present at or around the time of birth.

Hereditary and developmental conditions not obvious at birth can become manifest later in life.

Concepts of developmental anomalies

• Teratology is the study of developmental anomalies that take place during fetal development

• "e agents that cause developmental anomalies are called teratogens

Teratogens

• Alcohol

• Tobacco

• Cocaine

• Heroine

• Warfarin

• Tetracycline

• Maternal diabetes

• Maternal folic acid deficiency

• SLE

Overview of Genetic Concepts

• Chromosomes

• Genes

Chromosomes

• "e DNA molecule is packaged into thread-like structures called chromosomes.

• Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure.

Genes

• Gene is a molecular unit of heredity of a living organism

• It is a name given to some stretches of DNA and RNA that code for a polypeptide

Control genes play key roles in

• organ formation and the pa#erning of structures throughout the embryo

• regulate the signaling pathway between cells & tissues

vidual. How the specific individual’s body functions andwhat the person looks like physically is called the pheno-type. When the alleles at a specific locus are identical, theindividual is said to be homozygous for that genetic trait,when they are different, the individual is heterozygous forthe trait. Some genes are dominant, that is they will expressthe trait whether the individual is homozygous or het-erozygous for that trait. To the contrary, identical recessivegenes must be present in both alleles for a recessive trait tobe expressed. An individual who is heterozygous for a par-ticular genetic trait may be a carrier of a recessive trait, dis-order, or disease. Carriers do not usually exhibit character-istics of the gene in their phenotype, but they are able totransmit the gene to the next generation. If the partner ofthe carrier is also a carrier, then it is possible to have a childwho will exhibit the full phenotypic expression of the re-cessive trait. Occasionally carriers will benefit from beingheterozygous or having one recessive gene and one domi-nant gene, as is the case with sickle cell trait (Chapter 9).

Intermediate expression occurs when an individualwho is heterozygous for a particular trait exhibits neither ofthe homozygous phenotypes but exhibits a trait somewherebetween the two. For example, male voice pitch is con-trolled by a specific gene; when the alleles are homozygous,the voice is either a high or low pitch, when the alleles are

CHAPTER 6 • DEVELOPMENTAL, HEREDITARY, AND CONGENITAL DISORDERS 119

Figure 6.7. X Chromosome with the loci of specific genesidentified. The location of representative inherited disor-ders on the X chromosome. Genes that are located at thesame locus on homologous chromatids are called alleles.(From Rubin E, Farber JL. Pathology. 3rd ed. Philadelphia:Lippincott Williams & Wilkins, 1999.)

Figure 6.8. Normal male and female karyotypes. Photomicrographs of human chromosomes arranged in a standard classifi-cation. If a blood sample is taken from a child or adult and the white blood cells are examined at the mitotic division phaseof reproduction, transferred to slides, and photographed under high-power magnification, the individual chromosomes canbe cut from the photograph and arranged according to size and shape. A. Normal female karyotype. B. Normal male kary-otype. (From Pillitteri A. Maternal and child nursing. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2003.)

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Few Facts

• Teeth form from cooperative interaction of two germ layers, ectoderm and ectomesenchyme (neural crest derivative)

• Enamel is formed from ectodermal components

• Dentin, Pulp, Cementum, the supporting PDL and bone are all derived from ectomesenchyme

Disorders of development of teeth

"e development of teeth and associated structures are regulated by genes, but the genetic program is very sensitive to disturbances in the environment such as infections or toxic chemicals.

Disorders of development of teeth

• Disturbance in number of teeth

• Disturbance in size of teeth

• Disturbance in form of teeth

• Disturbance in structure of teeth

Disturbance in number of teeth

• Hypodontia

• Anodontia

• Hyperdontia (supernumerary)

• Hypohidrotic ectodermal dysplasia

Hypodontia

• congenital absence of teeth

• one or several teeth are missing

Anodontia

• when there is complete absence of one or both dentitions

Hypodontia

• Genetic basis not yet understood

• several regulatory genes involved in tooth involvement, mutations in these genes is likely to be responsible.

• more common in the permanent dentition (2-10% of population)

• in primary dentition prevalence is less then 1%

Hypodontia

Symmetrically missing:

• third molars

• permanent maxillary lateral incisors

• mandibular second premolars

Hypodontia

• more common in females

• may be symmetrical

• unusual for deciduous teeth to be congenitally missing > permanent dentition will also fail to form

• severe hypodontia / anodontia may be associated with other developmental abnormalities

Hypodontia

• teeth additional to those of normal series

• may develop in tooth bearing areas

• frequent in anterior & molar regions of maxilla

• premolar region of the mandible

• cle$ palate, cleidocranial dysplasia

• may prevent eruption, may develop dentigerous cyst if unerupted

• more common in females

• occur in single

• about 1-3% of population

• present in deciduous dentition

Mesiodens

• Supernumerary teeth occurring in certain sites may be referred by special terms.

• Supernumerary teeth developing b/w the maxillary central incisors

• most common form

• conical crowns & short roots

Mesodens

Paramolar

• arises alongside maxillary molars

• usually buccally placed

Distomolar

• develops distal to a third molar

Distomolar

Supplemental teeth

• morphologically resembles those of normal series

• mostly reduced in size

Ectodermal dysplasia syndrome

• is not a single disorder

• a group of syndromes all deriving from abnormalities of ectodermal structures

• more then 150 syndromes

• Heritable conditions in which there are abnormalities of two or more ectodermal structures such as the hair, teeth, nails, sweat glands, cranial-facial structure, digits and other parts of the body.

Ectodermal Dysplasias: A Clinical And Genetic Study.

Abnormal structures:

• Hair

• Nails

• Skin

• Sweat Glands

• “Anhidrotic ectodermal dysplasia," and "Christ-Siemens-Touraine syndrom

• have reduced ability to sweat because of fewer sweat glands

• sparse hairs on scalp and body

Distinctive facial features including

• prominent forehead

• fla#ened bridge of the nose

Additional features include

• thin, wrinkled, and dark-colored skin around the eyes

• chronic skin problems such as eczema

• bad-smelling discharge from the nose

Teeth

• tooth buds frequently absent

• or growth of teeth that are peg shaped or pointed

• enamel may be defective

• multi disciplinary approach is required

Disturbances of size of teeth

• size of both jaw & teeth influenced by genetic & environmental factors

Microdontia

• teeth in the dentition appear smaller then normal

• or may be relatively small in comparison with a large mandible & maxilla

• may involve entire dentition or one or two teeth

• Autosomal dominant inheritance pa#ern

Macrodontia

• generalized is characterized by the appearance of enlarged teeth throughout the dentition

• may be absolute as seen in pituitary gigantism

• or may be relative owing to a disproportionately small maxilla and mandible would result in crowding

Disturbances in form of teeth

Disturbances in tooth form may involve

• Crown

• Root

• Or both

• frequent variations of the crowns affect maxillary permanent lateral incisors

• Premolars or molars with an increased or decreased number of cusps are also frequently seen

Dilaceration

• an extraordinary curving or angulation of tooth roots

• cause of this condition has been related to trauma during root development

• most frequently involves maxillary incisors

Flexion

• is a deviation or bend restricted just to the root porion of the tooth

• bend is less then 90 degrees

• result of trauma

Flexion

Taurodontism (bull-like tooth)

• Pulp chamber has a greater apico-occlusal height than in normal teeth with no constriction at the level of amelo-cemental junction

• "e result is that the chamber extends apically, well beyond the neck of the tooth

• affects multi rooted teeth

• caused by failure of Hertwigs sheath to invaginate at proper level

• rare in primary dentition

Taurodontism

Dens in Dente

• Also called Dens Invaginatus

• means tooth with in a tooth

• uncommon developmental anomaly

• primarily affects maxillary lateral incisors

• deeply invaginated lingual pit

• susceptible to caries, if le$ una#ended tooth will decay very rapidly

Double teeth

• Descriptive term used to describe a developmental anomaly where two teeth appear joined

• degree of union is variable may involve crown, root or both

• Incisors canines in the primary dentition

• more common in the primary dentition

Fusion

• Fusion is the joining of two developing tooth germs resulting in a single large tooth structure

• entire length of the teeth

• may involve only roots, in which cementum & dentin are shared

Gemination

• is the fusion of two teeth from a single enamel organ

• result is a partial cleavage, with the appearance of two crowns that share the same root canal

Concrescence

• Concrescence is an acquired disorder in which the roots of one or more teeth are united by cementum

• may take place before or a$er eruption

• most commonly seen in association with the maxillary 2nd & 3rd molars

Disturbances in structure of teeth

• Defects of the teeth like pi#ing or discoloration are mostly the markers of past diseases systemic or localized.

• It is very un-common that the disease process which caused the defect in tooth structure is still active.

Amelogenesis

Enamel normally develops in two stages

• Secretory stage

• Maturation stage

Secretory stage

In this stage Ameloblasts perform dual function;

• Matrix production

• Initial mineralization

Matrix production involves synthesis and secretion of

• Enamel proteins mainly enamelin and amelogenin

• Initial mineralization occurs immediately a$er the secretion of enamel proteins

Maturation stage

• "is stage involves withdrawal of water and proteins from the enamel and a concomitant increase in the mineral content.

Disturbances in the enamel formation can be classified accordingly;

• Hypo plastic enamel; disturbances in the production of enamel matrix

• Hypo mineralized enamel; disturbances in the initial mineralization and maturation

Hypoplastic enamel

• In this condition ameloblasts fail to produce a normal volume of matrix

• However, any matrix which is produced generally becomes fully mineralized as normal enamel

• Clinical features:Pits or groves on enamel surface, or a general reduction in the thickness of whole of the enamel

Generalized pi#in & Smooth Surface

Hypo-mineralized Enamel

• It results from a failure of ameloblasts to fully calcify the previously formed matrix

• Clinical features: White and opaque, a$er eruption it may become pigmented buff, orange, or brown and be quickly chipped and worn away

• Hypo mineralized and hypo-plastic enamel defects may involve a single tooth, a group of teeth or all of the teeth, and the structure of the enamel formed depends on the severity and duration of the disturbance and its nature

Disturbance in structure of enamel

Abnormalities of the enamel can be classified as;

Local causes:

• Infection

• Trauma

• Radiotherapy

• idiopathic (enamel opacities)

General causes:

1.Environmental/Systemic (chronological hypo-plasias)

A.Pre-natal:

I.infections e.g. rubella, syphilis

II.maternal disease

III.excess fluoride ions

B.Neo-natal:

I.Haemolytic disease of the newborn

II.Hypocalcaemia

III.Premature birth/prolonged labour

C.Post-natal:

I.Severe child hood infections

II.Chronic diseases in child hood e.g. congenital heart disease

III.Nutritional deficiencies, e.g. vitamin D

IV.Cancer chemotherapy

V.Excess fluoride

2.Genetic:

A.Teeth only affected:

• Amelogenesis imperfecta

B.Teeth affected in association with generalized defects:

• Ectodermal dysplasia syndrome

• Down syndrome

Amelogenesis Imperfecta

• ‘Amelogenesis imprfecta is a genetic abnormality of the enamel formation which only affects the amelogenesis’

• All types of amelogenesis imperfecta affects the deciduous and permanent dentition.

It is classified into 2 distinct types.

• Hypo mineralized type

• Hypo plastic type

Hypo mineralized type is further divided into 2 types.

• Hypo maturation type

• Hypo calcified type

Hypo calcified type

• Is the most common form of this disorder

• Newly erupted teeth appear normal in size and shape and have enamel of normal thickness

• Enamel is of a so$, chalky consistency and is rapidly lost by a#rition and abrasion, exposing the dentin.

• Gross a#rition is a feature of it, and the teeth may be worn down to gingival level.

• Enamel has a similar density to dentin in radiographs.

Hypo maturation type

• In this type the enamel is generally of normal on eruption but exhibit variable opaque, mo#led, brownish-yellow to white appearance

• Enamel is so$ and a#rition occurs but not as severely as in hypo calcified type

Hypo plastic type

• In this for enamel does not reach to the normal thickness and there is a considerable variation in the clinical appearance.

• In some cases localized areas of hypoplasia are randomly distributed over the surface of the enamel producing generalized roughness and pi#ing or irregular grooving and wrinkling.

• In the smooth form, enamel over the whole of the crown is affected and the teeth have sharp, needle like cusps.

• Enamel is very thin but hard and glassy

Dentinogenesis Imperfecta

• Most of the clinically significant disturbances of dentinogenesis have a genetic etiology, but some environmental or systemic disturbances affecting calcium metabolism or calcification may also produce abnormal dentin.

Local Cause General Causes

Dentinogenesis Imperfecta

Type I - osteogenesis imperfectaType II -Teeth only affected

(Shell teeth)Type III - Brandywine Isolate

(DSPP gene)

Dentine dysplasia

Type I - radicular dentine dysplasia

Type II - coronal dentine dysplasia

Enviormental

Vit-DHypophosphotasia

Juvenile hypoparathyroidism

Other mineral deficiencies

• "is uncommon defect of collagen formation is transmi#ed as an autosomal dominant trait.

• "e dentin is so$ and has an abnormally high water content.

• "e enamel appears normal but uniformly brownish or purplish and abnormally translucent.

• "e crowns of the molars tend to be bulbous and the roots are usually short.

• Enamel is weakly a#ached to the dentine and tends to chip away very easily.

• In severe cases the teeth become rapidly worn down to the gingival level.

• Radiological examination shows short, blunt roots with partial or complete obliteration of the pulp chambers and root canals by dentine.

• Histological examination shows that the dentine contains a reduced number of tubules and areas of a-tubular dentin may also be present. "is abnormal dentine partly or totally obliterates the pulp chamber and root canal.

• Biochemical analysis shows an increased water and decreased mineral content.

• "e hardness of the of the dentine is low explaining the rapid a#rition of teeth which occurs following loss of enamel.

• Caries is un-usual in affected teeth, presumably due to the reduced number of invasion pathways in the dentin.

Shell Teeth

• "is rare anomaly is so called because only a thin shell of hard dental tissue surrounds overlarge pulp chamber

• appears to be a variant of dentinogenesis imperfecta

• normal, but thin mantle dentine which covers irregular dentine.

• Pulp lacks a normal odontoblast layer and consist of coarse connective tissue which becomes incorporated into the deep surface of the dentine.

References

• J. V. Soames, J. C. Southam, “Disorders of development of teeth and craniofacial anomalies” in Oral Pathology, 4th Edition, Oxford University Press, 2007 pp 1-15.

• Leslie DeLong, Nancy W. Burkhart, “Developmental, Hereditary and Congenital Disorders” in General Oral Pathology for Hygienists, 1st Edition, Lippinco# Williams and Wilkins, 2008 pp 110-146.