ADA.org: Future of Dentistry Full Report

FUTURE OFDENTISTRY

and an increased demand for insulin, apparently a
consequence of insulin resistance (insulin toler-
ance). The metabolic stress of infection shifts a
person with normal glucose tolerance towards a
pre-diabetic state of type 2 diabetes. It has been
suggested that this metabolic effect is a conse-
quence of systemic LPS, TNF and IL-1, and IL-6,
all of which enhance insulin resistance. Experi-
ments are underway to definitively determine
whether periodontal therapy reduces the need for
insulin in diabetics and reduces the risk for the
onset of type 2 diabetes.

Animal Models

Animal models of infections with periodontal
pathogens and experimental periodontitis have
demonstrated the deleterious effect of infection on
atherosclerosis, diabetes, and fetal growth (Collins
et al, 1994a; and Lalla et al, 1998). These data not
only help establish biological plausibility but also
provide important clues regarding the mechanisms
of cellular and molecular pathogenesis.

CLEFT LIP, CLEFT PALATE AND CRANIOFACIAL
DEVELOPMENTAL DISORDERS

Orofacial clefting is the second most common
birth defect (CDC, 1995), and the most frequent of
all birth defects affecting the craniofacial region.
Only congenital heart defects occur more often.
Oral clefts are classified and distinguished into
two major types based on whether the palate only
versus the lip or both the lip and palate are involved
(Gorlin et al, 1990; OMIM, 2001; and Cohen,
2000). This classification reflects the embryologi-
cally distinct events of closure of the lip versus
closure of the palate. These two major types of
clefting are caused by substantially different
genetic and environmental factors, although recent
evidence suggests that some overlap in etiology
also exists.

u Isolated cleft palate(CP) is a cleft affecting the
palate only, posterior to the incisive foramen.
They may affect the soft palate only, or both hard
and soft palates. This category includes submu-
cous cleft palate where the cleft affects the mus-
culature of the soft palate but with intact overlying
mucosa. Isolated clefts of the palate represent
approximately 33% of all clefts.

u Cleft lip with or without cleft palate(CL/P) are

clefts affecting the lip and sometimes also the

adjacent maxillary alveolus, or alveolus and palate, typ-

ically in the vicinity of the lateral incisor. They may be

partial or complete, and unilateral or bilateral. Clefts

of the lip, with or without alveolar clefts, represent

approximately 17% of all clefts. This condition may

occur with cleft palate. Complete lip, alveolar and

palate clefts represent approximately 50% of all clefts.

An important distinction is also made depending on

whether or not other major or minor physical or

mental/neurological anomalies also affect the patient.

u Syndromic cleftsinvolve the presence of one or

more physical and/or mental/neurological patterns of

abnormalities in addition to the cleft. The presence

of minor anomalies or of major anomalies that might

be unrelated to the etiology of the cleft occasion-

ally makes classification uncertain. About 30% of

orofacial cleft cases are attributed to the over 350

syndromes recognized to date.

u Nonsyndromic oral cleftsoccur without any

physical or mental/neurologicalanomalies. Approxi-

mately 70% of oral clefts appear to be nonsyn-

dromic.

Most oral cleft syndromes have a major heredi-

tary cause (Gorlin et al, 1990; and Cohen, 2000).

Purely environmental causes are relatively rare, and

even these may be affected by genetic differences

influencing metabolism of teratogens following

maternal and fetal exposures. About 55% of the

syndromes associated with syndromic clefting have

a monogenic autosomal dominant or recessive or X-

linked mode of transmission, 15% involve chromoso-

mal rearrangements, about 5% have primarily an

environmental (i.e., teratogenic) etiology, and the

cause for the remaining 25% is unknown. The specif-

ic gene defects for some of the monogenetic syn-

dromes have been identified, such as three different

collagen genes for the three types of Stickler syn-

drome. Genes for other syndromes, such as van der

Woude, have been mapped to a small chromosomal

region, and gene identification is expected soon.

The causes of nonsyndromic orofacial clefting

involve complex gene-environment interactions

(Schutte and Murray, 1999; and Carinci et al,

2000). To date, only a very small number of candi-

date gene polymorphisms have been evaluated.

Dental and Craniofacial Research