Orofacial Genetics for Dentists

Orofacial Genetics for Dentists

• Orofacial Genetics is a field crucial for dentists
• Genetics plays a role in conditions like caries, periodontal disease, dental anomalies (like cleft lip and palate), malocclusion, and oral cancer.
• Molecular genetics will be used to diagnose and treat many of these diseases.

Biomarkers for Oral Cancer

• S100A7 is a predictive marker for premalignant oral lesions (e.g., leukoplakia, lichen planus).
• It plays a role in epithelial, breast, thyroid cancer, and Alzheimer's disease.

Genetics and Caries

• Twin studies suggest a genetic influence on caries, with a 20% to 85% partial genetic control.
• Variation in caries experience is due to genetic and environmental differences between populations or races.
• Early childhood caries is related to maternal health (e.g., obesity, diabetes).

Genes Involved in Caries

• Genes like MMP20 (Matrix Metalloproteinase 20), AMBN (Ameloblastin), AMELX (Amelogenin), ENAM (Enamelin), KLK4 (Kallikrein 4), AQP5 (Aquaporin 5), CA6 (Carbonic Anhydrase VI), and MUC5B (Mucin 5) influence tooth development, mineralization, saliva production, and biofilm formation.
• These genes impact caries susceptibility and various dental conditions.

Genetics and Periodontal Disease

• Monogenic syndromes—like Papillon-Lefèvre and Chediak-Higashi syndromes—cause aggressive periodontitis.
• Periodontal disease results from genetic susceptibility and bacterial challenge; it involves both structural integrity and host response to bacteria.
• A 2017 review indicated the vitamin D receptor (VDR), interleukin-10 (IL-10), and Fc-yRIIA gene as strong candidates.

Papillon-Lefèvre Syndrome (PLS)

• PLS is a rare autosomal recessive disorder.
• This disorder features diffuse palmoplantar keratoderma.
• PLS also features precocious aggressive periodontitis affecting deciduous and permanent teeth.
• This condition leads to premature tooth loss.

Genes Involved in Periodontal Disease

• Fc-YRIIA (platelet receptor), IL-1 (proinflammatory response), IL-6 (proinflammatory response affecting bone resorption), IL-8 (immune response), IL-10 (immune response), IL-37 (immune response), MMP2, 3, 8, 9 (extracellular matrix degradation), and VDR (tooth formation, calcium, and phosphate balance) have roles in periodontal disease.

Personalized Medicine

• Dental and medical care require examination, diagnosis, and treatment prescription.
• Patients may not respond equally to treatments.
• Individual responses are likely determined by intrinsic genetic factors and behavior (e.g., lifestyle, diet, exercise).

Personalized Orthodontics

• Genetic tests can help predict treatment outcomes in orthodontics.
• Polymorphic studies can reveal high risks of external apical root resorption and malocclusion.
• Identifying individuals with different skeletal growth responses helps tailor treatment.

Variation in the Human Genome

• 99.9% of DNA bases are identical between individuals.
• The remaining 0.1% variation creates individual differences.
• This variation correlates with appearance and susceptibility to various diseases.

What are Variation Types in the Genome?

• Genome variations include polymorphism, deletions, insertions, and chromosome translocations.

Polymorphism

• Genetic variations observed at a >1% frequency in a population.
• Single-nucleotide polymorphisms (SNPs) are common and are single-base substitutions.
• SNPs are often found in DNA between genes and can be used as biological markers for disease risk or response to treatment.
• Some SNPs have no effect on health or development, while others impact drug response, susceptibility to toxins, and disease risk.
• SNPs can track disease gene inheritance within families.

Tandem Repeat Polymorphisms (VNTRs)

• VNTR are genetic variations involving repeated sequence motifs, whose copies are tandemly repeated.
• Types include microsatellites (1-6 repeat units, e.g., CACACACACA) and minisatellites (14-100 repeat units).

SNPs in Linkage Analysis

• SNPs' segregation patterns alongside disease traits reveal candidate genes.
• DNA from affected and unaffected family members reveals SNP patterns.

SNPs in Association Studies

• SNP allele frequencies are compared between patients and healthy controls.
• This checks if a particular SNP is linked to the disease.

Causes of Human Congenital Anomalies

• Congenital anomalies have various causes.
• Unknown etiology contributes around 50-60%
• Multifactorial inheritance contributes around 7-10%.
• Chromosomal abnormalities contribute around 7-8%
• Mutant genes contribute around 20-25%.
• Environmental agents contribute to the rest, around 4-9%.

Mutations

• Different mutation categories (e.g., substitution, deletion, insertion) exist.
• Mutations can result in various biological effects, such as protein generation changes.

Single Base Substitutions

• Changes in amino acid sequences can result from substituting one nucleotide with another in a codon.
• Single base mutations don't disrupt the genetic frame.
• Frameshift mutations disrupt the amino acid sequence.

Deletions and Insertions

• Single base deletions or insertions shift the entire genetic frame.
• Deletions or insertions result in incorrect protein production.

Splice Mutations

• Mutations interfering with intron removal from messenger RNA.

Mutations in Regulatory Sequences

• Mutations affecting crucial gene regulation regions (e.g., TATA box, CAT box).

Single Gene Disorders

• Single gene mutations transmitted through Mendelian inheritance.
• Inheritance patterns depend on chromosomal location (autosomal or X-linked) and allele dominance/recessiveness.
• Four major inheritance types exist: autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive.

Mendelian Disorders (Dental and Craniofacial)

• Dental disorders include amelogenesis imperfecta, dentinogenesis imperfecta, familial hypodontia, and other ectodermal dysplasias.
• Craniofacial disorders include cleidocranial dysostosis, nevoid basal cell carcinoma syndrome, craniosynostosis syndromes, and oro-facial clefitng syndromes.

Mendelian Disorders (Systemic)

• Systemic disorders like sickle-cell anemia can impact dental care due to increased infection susceptibility, delayed eruption, hypoplasia, hypercementosis, and osteoporosis. Cystic fibrosis can also cause side effects related to antibiotics.

Autosomal Dominant Inheritance

• One defective allele is sufficient for the condition to develop.
• Affected individuals usually have one defective and one normal allele.
• New mutations, variable expressivity, late onset, and incomplete penetrance contribute to the presence of the disease in the population.

Variable Expressivity (Example: Marfan Syndrome)

• Marfan syndrome, caused by collagen mutations, affects individuals differently, with variable severity and symptoms.

High Recurrent Mutation Rate

• Some conditions (like achondroplasia) maintain affected genes in populations due to high mutation rates.

Incomplete Penetrance

• Incomplete penetrance means not all individuals with a mutation develop the associated trait.
• Some mutations may increase the risk but not always manifest the disease.

Crouzon Syndrome

• An autosomal dominant condition with complete penetrance, often due to sporadic mutations.
• Features craniosynostosis and facial structure changes.
• Specific facial and hand features may also be present.

Cleidocranial Dysplasia

• Autosomal dominant disorder featuring unerupted/delayed teeth, multiple/supernumerary teeth, and characteristic facial features (e.g., frontal bossing, hypertelorism).
• Clavicles often hypoplastic or absent.
• This condition involves a mutation in the CBFA1 gene in bone development.

Autosomal Recessive Inheritance

• Two copies of a mutated gene are required for the condition (homozygosity).
• Parents typically don't exhibit the characteristic features (are heterozygous).
• Consanguineous marriages (between relatives) increase the risk of recessive conditions.

Amelogenesis Imperfecta

• Genetic mutations in various genes (e.g., AMELX, ENAM, MMP20, KLK4) can result in various forms of amelogenesis imperfecta.
• Inheritance patterns vary based on the affected gene.

Explore the crucial role of orofacial genetics in dentistry, including genetic influences on oral diseases and conditions such as caries, periodontal disease, and oral cancer. This quiz focuses on key genetic markers and their implications for diagnosis and treatment in dental practice.