GenF Testing and Evaluation Flashcards
What is the title of book on medical genetics written by Dr Robert Gorlin that remains an important work even today?
“Syndromes of the Head and Neck”
What are some challenges in genetic diagnosis?
Variable expressivity
incomplete penetrence
Genetic heterogeneity
Age on onset of varying clinical features
Chronic (occasionally progressive) in nature
What is the term for respect for individual independence?
Autonomy
What is the term for the act of doing good?
Beneficence
What is the term for respect for privacy?
Confidentiality
What is the term for fairness, conforming to the principles of right and wrong?
Justice
What are six parts of genetic evaluation?
- Family history
- Med record review
- Physical exam of major systems, fine details, measurements
- Lab and radiography
- Compare to databases / literature / experiences
- Review with collegues
What is the term for is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease?
Genetic counseling
What are three reasons dental professionals are key in genetic evaluation and testing?
- Often see adolescent and pre- adolescent children more often than the physician.
- Are experts on the face and mouth and can be most skilled and observing anomalies
- Provide valuable service to patient’s by referral to Medical Geneticists and Genetic counselors
What are 3 criteria for genetic testing?
- Analytic Validity
- Clinical Validity
- Clinical Utility
What does the term analytic validity mean?
Results are accurate and precise
What does the term clinical validity mean?
Ability of the test to predict the disease phenotype
What does the term clinical utility mean?
The phenotype can be modified based on test results
What are 3 general uses of genetic testing?
- Clinical – for diagnosis, prevention, treatment
- Research – for improved understanding and development of clinical test
- Investigational – may be of value but not yet generally accepted by third party payors
What are five general types of genetic testing?
- Chromosomal
- FISH
- CGH (Comparative Genomic Hybridization)
- DNA
- Biochemical
True or False: Except for chromosomes and now comparative genomic technologies, most molecular tests are quite specific and not screens
True
True or False: Biochemical testing (maternal serum screen in pregnancy, newborn screen with tandem mass spectrometry) may be broader screens, but lower specificity
True
Genetic testing is best when coupled with what?
Genetic counseling
What are 2 things genetic test results are used for?
- Medical management
2. Personal decision making
What is the term for the use of genetic testing to confirm or rule out genetic condition in a symptomatic individual?
Diagnostic
What is the term for genetic testing offered to at risk ASYMPTOMATIC individuals?
Predictive
If development of symptoms is certain, person is said to be what?
Presymptomatic, e.g. Huntington’s disease
True or false: Testing of asymptomatic children at risk for adult-onset conditions is strongly encouraged when no treatment is available
FALSE: It is strongly DIScouraged
What is the term for when development of symptoms is likely, but not certain?
Predispositional, e.g BRCA1, BRCA 2 (Breast cancer susceptibility genes)
Diagnostic info in symptomatic individual can be used for what?
Alter management, family planning (e.g. Duchene’s Muscular dystrophy, cystic fibrosis, fragile X, 22q11 deletion)
What is offered to asymptomatic individuals in order to identify those with an increased risk for developing or transmitting a genetic condition
Genetic screening
What type of genetic testing is usually for asymptomatic individuals?
Carrier
What type of genetic testing is performed during pregnancy to assess health of fetus?
Prenatal
What type of genetic testing is performed on early embryos after in vitro fertilization but before implantation into the uterus?
Preimplantation
What are some abuses of genetic testing?
- Testing limitations – sensitivity, specificity, accuracy
- Genetic susceptibility is not health destiny
- Limitations in available treatment
- Potential for discrimination
- Lack of privacy, autonomy
What should be considered when ordering a genetic test?
Clinical utility
Analytic and clinical validity Ethical-legal-social implications Relationship to health outcomes
Commercial testing is available for what three things related to the oral cavity?
- Type and concentration of peri-pathologic bacteria
- Susceptibility to periodontal disease
- Oral HPV
What are five additional uses of DNA technology?
- Identity
- Forensics
- Parentage
- Zygosity
- DNA banking
The Periodontal Disease Susceptibility Genetic test looks for what
Polymorphisms on IL1a and IL1b
What protections are there for genetic information?
Americans with Disabilities Act HIPPA State Law Institutional Review Boards Genetic Information Nondiscrimination Act (GINA)
What is the CHARGE syndrome acronym?
C Coloboma of Eye (hole in eye structure)
H Heart defects
A Atresia of the choanae (back of nasal passage blocked)
R Retardation of growth and or development
G Genital or urinary defects
E Ear anomalies
What is a concern with cranial nerve dysfunction in CHARGE syndrome?
Swallowing problems, aspiration
What is the common appearance of the ears of a person with CHARGE syndrome?
Lobeless, inner ear problems
What are some dental problems in CHARGE syndrome?
Prognathic, overbite, hypodontia permanent dentition, poor mineralized enamel
What do the hands of a patient with CHARGE syndrome look like?
Square short fingers, hockey stick palmer creases
What are the Blake criteria for clinical diagnosis of CHARGE?
4 major or 3 major + 3 or more minor
What are the 4 major criteria for CHARGE diagnosis?
- Coloboma or micropthalmia
- Choanal atresia or stenosis
- Typical ear anomalies
- Cranial nerve dysfunction
What are the 6 minor criteria for CHARGE diagnosis?
- Genital hypoplasia
- Delayed development
- Heart malformations
- Clefts
- Tracheoesophageal fistula
- Distinctive face
What causes CHARGE?
A mutation of CHD7, codes chromatin helicase binding protein
Most common mutations in CHD7 cause what?
Protein truncation
What can be expected dentally for child with CHARGE?
Increased caries
What is important in diagnosis of CHARGE?
Genetic testing due to other genetic syndromes whose symptoms overlap
CD7 accounts for what percentage of CHARGE cases?
About 60%
What genetic test can be used to look for 22q11 deletion (cleft lip and or palate, heart defects, low T- cells, low Calcium, developmental delays) in order to differ out from CHARGE?
FISH diagnosis
What is a genetic syndrome that looks like CHARGE, but has different genetics. Symptoms are Vertebral anomalies, Anal defects (imperforate anus), Cardiac defects, Tracheoesophageal fistula, Renal/kidney anomalies, limb defects (absent radius, hypoplastic thumb), poor growth?
VACTERL
Do patients with CHARGE have a shorter or longer life expectancy?
Shorter
What pathology includes neural crest malformations in over half of external ear anomalies and missing external ear, cognitive problems, and is associated with retinoic acid/vitamin A containing medications?
Retinoic acid embryopathy
What causes cat eye syndrome?
22q duplications
Which syndrome includes the following:
MLL2 gene Hypotonia Mal-occlusion Cognitive disability GI motility problems Craniofacial dysmorphism
Kabuki syndrome
