INTRODUCTION ROLE OF THE PEDIATRIC DENTIST

IN GENETIC COUNSELING
Prenatal genetic counseling is provided for all
prospective parents, ideally before conception, to Pediatric Dentists treat children with Dentofacial
assess risk factors for congenital disorders. Parents anomalies and therefore should have a working
with risk factors are advised about possible knowledge of syndromology and molecular Genetics .
outcomes and options for evaluation . If testing Often Pediatric Dentists are the first health care
identifies a disorder, reproductive options are practitioner to document Dentofacial dysmorphic
discussed; preconception options include features in a child . It is thus important for them to
contraception, artificial insemination if the man is a have an u nderstanding of molecular genetics
carrier, and oocyte donation if the woman is a because the sensitivity and specificity of molecular
carrier; post conception options include pregnancy based diagnosis have revolutionized how disease and
termination and, in some cases, treatment (eg, disorders are defined . These specific and
Dexamethasone) . technological advances translate into improved health,
Risk factors: Some risk of genetic abnormality disease prevention, smarter diagnostics, and innovative
therapeutic approaches to Dentofacial dysmo
exists in all pregnancies . Among live births, incidence
rphogenesis . Dentist should work with the genetic
is 0.5 percent for numeric or structural chromosomal
counselor and radiologist to reach the conclusion of
disorders, 1 percent for single-gene (Mendelian)
molecular based diagnosis of the child, and take a
disorders, and 1 percent for multiple-gene (polygenic)
preventive and interceptive treatment plan for the
disorders.
abnormal dentofacial structure of a child (phenotype).
• Chromosomal disorders are more likely to be
Prior to molecular based diagnosis, craniofacial
present in fetuses that spontaneously abort during disorders were established based on characteristic
the 1st trimester (50 to 60%) , in fetuses with a features (pattern recognition), e.g. a child with a molar
major malformation (30%), and in stillborn (5%). hypoplasia, Mandibular retrognathia, down slanting
Genetic counseling is the process of : palpebral fissures, coloboma of the lower eyelid had
• Evaluating family history and medical records the clinical appearance of Treacher Collins
• Ordering genetic tests Syndrome. Although the common disorders were
• Evaluating the results of this investigation identifiable, there was difficulty in establishing the
• Helping parents understand and reach decisions diagnosis for all patients. Some had clinical
about what to do next characteristics that did not readily fit into a particular
Genetic tests are done by analyzing small samples syndrome or the condition was un common and
of blood or body tissues . They determine whether most clinicians were u naware of its
you, your partner, or your baby carry genes for existence .
certain inherited disorders, or not.
• With molecular diagnosis, it is now possible to • The mother-to-be has had two or more miscarriages
establish the correct diagnosis for most patients with or babies that died in infancy
craniofacial anomalies . Using this new tool it has • The mother-to-be 35 or older when the baby is
become evident that classification of craniofacial born . Chances of having a child with Down
malformations based on clinical features syndrome increase with the mother's age: a
(phenotype) is sometimes quite different from woman has a 1 in 350 chance of conceiving a
categorization by genetic findings (genotype) . child with Down syndrome at age 35, a 1 in 110
Patients with craniofacial syndromes may have chance at age 40, and a 1 in 30 chance at age
similar clinical phenotype that are caused by 45.
different mutations in a gene; identical mutations • You are concerned about genetic defects that occur
within a gene can cause widely different clinical frequently in certain ethnic or racial groups. For
phenotype. Additionally, mutations in different example, couples of African descent are more at
genes can cause similar clinical phenotypes. risk for having a child with sickle cell anemia;
Molecular-based diagnosis for complex craniofacial couples of central or eastern European Jewish
anomalies has truly transformed how we define (Ashkenazi), Cajun, or Irish descent may be carriers
these disorders. of Tay-Sachs disease; and couples of Italian,
Greek, or Middle Eastern descent may carry the
The Genetic Counselor gene for thalassemia, a red blood cell disorder.
The genetic cou nselor can help a person or family
understand their risk for genetic conditions (such as The Genetic Consultation
cystic fibrosis, cancer, or Down syndrome), educate the A genetic consultation involves evaluation of an
person or family about that disease, and assess the risk individual or family for one or more of the following
of passing those diseases on to children. reasons :
A genetic counselor will often work with families to • Confirming, diagnosing or ruling out a genetic
identify members who are at risk. If it is appropriate, condition
they will be advised for genetic testing, coordinate any • Identifying medical management issues
testing, interpret test results, and review all additional • Calculating and communicating genetic risks
testing, surveillance, surgical, or research options that • Providing or arranging for psychosocial support .
are available to members of the family.
Genetic counselors often work as part of a health At the Genetic Counseling Session
care team in conjunction with specially trained doctors, Genetics consultations usually involve one or more
social workers, nurses, medical geneticists, Pediatric visits and phone calls with genetic counselors .
dentist or other specialists to help families make Occasionally, consultations can take place in groups
informed decisions about their health . They also work (e.g. cancer or prenatal consultations) or by phone
as patient advocates, helping individuals receive (e.g. routine or uncomplicated matters) .
additional support and services for their health care 1. Assessment: Gathering information
needs. • Explore with the patient and family:
Experts recommend that all pregnant women, - Reason for referral
regardless of age or circumstances, be offered genetic - Understanding of genetics
counseling and testing to screen for Down syndrome. - Diagnoses under consideration
It's especially important to consider genetic counseling - Perception of disease status or risk
if any of the following risk factors apply to you : - Beliefs about cause of disease
• A standard prenatal screening test (such as the - Perception of disease burden
alpha fetoprotein test) yields an abnormal result • Document patient 's birth history, past medical
• An amniocentesis yields an unexpected result (such history and current status.
as a chromosomal defect in the unborn baby) • Obtain directed family history in pedigree form
• Either parent or a close relative has an inherited using standing symbols, including :
disease or birth defect - The patient's first degree (children, siblings,
• Either parent already has children with birth defects parents) and second degree (grandparents,
or genetic disorders
S. No. Ethnic group Disorder Screening test Prenatal diagnosis
1. All Cystic fibrosis DNA Analysis of 25 CFTR CVS or amniocentesis
Mutation , which are
Present in > 0.1% population
2. Blacks Sickle cell anemia Screening test for sickle cell, CVS or amniocentesis for
hemoglobin , confirmatory Genotype determination
hemoglobin , electrophoresis . (direct DNA analysis)
3. Mediterranean people Beta-thalassemia MCV < 80% followed by CVS or amniocentesis for
hemoglobin , electrophoresis . Genotype determination
(direct DNA analysis or
linkage analysis)
4. South east asians Alfa-thalassemia MCV < 80% followed by CVS or amniocentesis for
hemoglobin , electrophoresis genotype determination (direct
DNA analysis or linkage analysis)

grandchildren, aunts, uncles, nieces, • Discuss reproductive options, if and when

nephews) relatives, and further removed as appropriate, which may include :
appropriate - Pregnancy with prenatal testing
- Status of current pregnancies - Pregnancy without prenatal testing
- Ethnic background Remaining childless
- Presence of consanguinity - Parenting by adoption
2. . Symbols for constructing a family pedigree . - Pregnancy by egg or sperm donation
3. Genetic screening for some ethnic groups (Table
- Pregnancy following preimplantation genetic
40 .1)
diagnosis
4. Evaluation: Interpreting medical and family history,
6. Support: Helping the family to cope
results of physical examination and tests
• Recognize and discuss the emotional responses
• Consult relevant references .
• Compare patient 's history and examine to know of family members to information given (which
diagnosis. may include shock, disbelief , relief, fear, guilt,
• Discuss diagnostic impression . sadness, shame, and acceptance) .
- Clear diagnosis - Share information about • Review normal grief responses and signs that
the condition might indicate the need for further psychosocial
- Differential diagnosis - Suggest further tests support.
or evaluations • Listen to the whole story, and hear what this
- Unknown diagnosis - Discuss what known situation has meant to the family.
diagnoses are ruled out, follow over time • Explore strategies for communicating
5. Communication: Sharing information about the information to others, especially family
condition (within the family's ability to understand members who may be at risk.
the information) Provide written materials and referrals to support
• Review the details about the disorder in groups, other families with the same or similar
question including : condition, with the help of local and national service
- Expected course of the disease agencies .
- Management issues, and possible treatments 7. Follow-up: Maintaining ongoing communication
or interventions • Arrange for follow-u p d iagnostic testi ng or
- Underlying genetic cause if known, management appointments, or communicate this
including pattern of inheritance need to the referring healthcare provider.
• Describe risks to family members compared • Document the content of the consultation for the
with general population risks . referring healthcare provider and for the patient
when appropriate .
 • Contact the patient to assess level of under Genetic Testing: A genetic test is the analysis of human
standing and response to decisions made . DNA, RNA, chromosomes, proteins, or certai n
• Encourage family to re-contact the clinic when metabolites in order to detect alterations related to a
considering pregnancy or for updated inheritable disorder. This can be accomplished by
information . directly examining the DNA or RNA that makes up a
• Be available to answer future questions . gene (direct testing), looking at markers co-inherited
Genetic counseling sessions do not include : with a disease causing gene (li nkage testing) ,
• Any testing or procedures that you do not explicitly assaying certai n metabolites (biochemical testing),
approve or examining the chromosomes (cytogenetic testing) .
• Prescriptions : In most cases, genetic counselors are Although, genetic testing shares some features in
not medical doctors and do not write prescriptions . common with other kinds of laboratory testing, in
• Specific medical recommendations : A genetic many ways it is unique and requires special
counselor will try to make sure that you fully considerations .
understand the risks, benefits, and possible • Genetic testing may be used for medical
consequences of every option that is available to management and for personal decision-making .
you . However, the genetic counselor will not make • Genetic test results usually apply not only to the
medical decisions for you . patient but also to other family members .
• Long-term psychological care: Although many genetic • Genetic testing may be performed in the context of
counseling sessions include follow-up sessions to a genetic consultation and should include informed
be sure that you are able to handle new
consent, test interpretation, and follow-up medical
information about your health, most genetic
and psychosocial services as indicated .
counselors are not trained to provide long-term
• Because most genetic disorders are rare, genetic
psychological care.
testing is often done only by specialized laboratories
Conclusion of genetic counseling; if you've learned .
prior to conception that you and/or your partner are • Intense research efforts in molecular genetics result
at high risk for having a child with a severe or fatal in the rapid development and availability of new
defect, your options might include : genetic tests; therefore, healthcare providers need to
• Pre-implantation diagnosis-When eggs that have continuously update their knowledge .
been fertilized in vitro (in a laboratory, outside of • In order for genetic testing to yield meaningful results :
the womb) are tested for defects at the 8-cell - Multiple test methodologies may be required
(blastocyst) stage, and only nonaffected blastocysts - Other family members may need to be tested
are implanted in the uterus to establish a - A genetic consultation may be appropriate
pregnancy
• Using donor sperm or donor eggs Genetic tests may be used for:
• Child adoption • Diagnostic testing
If you've received a diagnosis of a severe or fatal • Predictive testing
defect after conception, your options might include : • Carrier testing
• Preparing yourself for the challenges you'll face • Prenatal testing
when you have your baby • Preimplantation testing
• Fetal surgery to repair the defect before birth • Newborn screening.
(surgery can only be used to treat some defects, Research tests generally do not give clinically
such as spina bifida or congenital diaphragmatic applicable results. Research testing is discussed further
hernia, a hole in the d iaphragm that can cause in the "Ordering Genetic Testing" section .
severely u nder developed lungs. Most defects
Diagnostic Testing: Diagnostic testing is used to confirm
cannot be surgically repaired .)
or rule out a known or suspected genetic disorder in
• Ending the pregnancy
a symptomatic individual.
Points to be Kept in Mind Points to be Kept in Mind
• DNA testing may yield diagnostic information at a • Identifying carriers allows reproductive choices.
lower cost and with less risk than other procedures . • Genetic counseling and education should
• Diagnostic testing is appropriate in symptomatic accompany carrier testing because of the potential
individuals of any age. for personal and social concerns) .
• Confirming a diagnosis may alter medical • Molecular genetic testing of an affected family
management for the individual. member may be required to determine the disease
• Diagnostic testing of an individual may have
causing mutation(s) present in the family.
reproductive or psychosocial implications for other
• In some situations, DNA testing may not be the
family members as well .
primary way of determining carrier status.
• Establishing a diagnosis may require more than one
• Carrier testing can improve risk assessment for
type of genetic test DNA testing may not always be
members of racial and ethnic groups more likely to
the best way to establish a clinical diagnosis .
be carriers for certain genetic conditions .
Predictive Testing: Predictive testing is offered to
Prenatal Testing (Table 40.2): Prenatal testing is
asymptomatic individuals with a family history of a
genetic disorder. Predictive testing is of two types: performed during a pregnancy to assess the health
presymptomatic (eventual development of symptoms is status of a fetus. Prenatal diagnostic tests are offered
certain when the gene mutation is present, e.g. when there is an increased risk of having a child with
Huntington disease) and predisposition (eventual a genetic condition due to maternal age, family
development of symptoms is likely but not certain history, ethnicity, or suggestive multiple marker
when the gene mutation is present, e.g. breast cancer) . screen or fetal ultrasound examination. Routine
prenatal diagnostic test procedures are amniocentesis
Points to be Kept in Mind and chorionic villus sampling (CVS) . More specialized
procedures include placental biopsy, periumbilical
• Predictive testing is medically indicated if early
blood sampling (PUBS), and fetoscopy with fetal skin
diagnosis allows interventions which reduce morbidity
biopsy.
or mortality) .
• Even in the absence of medical indications,
predictive testing can influence life planning Points to be Kept in Mind
decisions • A laboratory that performs the disease-specific test
• Because predictive testing can have psychological
of interest must be identified before any prenatal
ramifications, careful patient assessment,
diagnostic test procedure is offered
counseling, and follow-up are important
• All prenatal diagnostic test procedures have an
• Many laboratories will not proceed with predictive
testing without proof of informed consent and associated risk to the fetus and the pregnancy;
genetic counseling . therefore, informed consent is required, most often
• Identification of the specific gene mutation in an in conjunction with genetic counseling.
affected relative or establishment of linkage within • In most cases, before prenatal diagnosis using
the family should precede predictive testing. molecular genetic testing can be offered, specific
gene mutation(s) must be identified in an affected
Carrier Testing: Carrier testing is performed to identify relative or carrier parent(s)
individuals who have a gene mutation for a disorder
inherited in an autosomal recessive or X-linked Prenatal testing includes the following:
recessive manner . Carriers usually do not themselves General Testing
have symptoms related to the gene mutation . Carrier • Blood Test
testing is offered to individuals who have family • Paternity Testing
members with a genetic condition, family members of • Urine Test
an identified carrier, and individuals in ethnic or racial • Ultrasound
groups known to have a higher carrier rate for a
• Rh Factor Testing.
particular condition .
 S. No. Indications Descriptions
Maternal age > 35 yr at expected delivery
Recurrent previous spontaneousChromosomal
abortion Analysis may be indicated for parents
Chromosomal abnormality in aChromosomal
previous child.
Analysis may be indicated for parents Need for genetic testing
Parental age > 50 yr. Balanced parental chromosomal aberrations may not required genetic testing
Parental chromosomal DisorderChorionic villus sampling, sometimes with ultrasound during the 1st or 2nd
the 2nd Trimester is done. Amniocentesis is done
6.
Levels of maternal serum marker
suggesting trisomy 21 and18th chromosomes during 1st or 2nd trimester Elevated maternal alfa-fetoprotein and
in determinant ultrasound results
7.

First Trimester Second Trimester

• Chorionic Villus Sampling (CVS) Diagnose fetal malformation
• First Trimester Screen • Weeks 13 to 14 for characteristics of potential
Second Trimester Down syndrome
• Amniocentesis • Weeks 18 to 20 for congenital malformations
• Cordocentesis : Percutaneous Umbilical Blood • Structural abnormalities
Sampling (PUBS) • Confirm multiple pregnancy
• Maternal Serum Alpha-Fetoprotei n Screening • Verify dates and growth
(MSAFP) • Confirm intrauterine death
• Quad Screen • Identify hydramnios or oligohydramnios -
• Triple Screen Test: Multiple Marker Screen excessive or reduced levels of amniotic fluid
• Evaluation of fetal well-being
Third Trimester
• Biophysical Profile ( BPP) Third Trimester
• Fetal Non-Stress Test (NST) • Identify placental location
• Glucose Challenge Screening and Glucose • Confirm intrauterine death
Tolerance Test (NST) • Observe fetal presentation
• Group B Strep Infection • Observe fetal movements
• Identify uterine and pelvic abnormalities of the
The ultrasound looks for: mother.
Ultrasounds are diagnostic procedures that detect or aid
in the detection of abnormalities and conditions related The chorionic villus sampling (CVS) test looks for :
to pregnancy . Ultrasounds are usually combined with Chorionic villus sampling detects chromosome
other tests, such as triple tests, amniocentesis, or abnormalities (i.e. Down syndrome) and genetic disorders
chorionic villus sampling, to validate a diagnosis . An (i.e. cystic fibrosis) .This test is different from
ultrasound exam is medically indicated throughout amniocentesis in that it does not allow for testing for
pregnancy for the following reasons : neural tube defects. Chorionic villus sampling also
provides access to DNA for paternity testing prior to
First Trimester delivery. DNA is collected from the potential father
• Confirm viable pregnancy and is compared to DNA obtained from the baby
• Confirm heartbeat during chorionic villus sampling. The results are
• Measure the crown-rump length or gestational age accurate (99%) for determining paternity.
• Confirm molar or ectopic pregnancies The amniocentesis test looks for :
• Assess abnormal gestation Amniocentesis detects chromosome abnormalities,
neural tube defects and genetic d isorders . Down
syndrome or Trisomy 21 is the most common In a pilot study to establish fetal nucleated red
chromosome abnormality . Genetic disorders include blood cell (NRBC) detection in maternal blood,
disorders like cystic fibrosis. The most common neural trisomy 13 was diagnosed by FISH analysis at 11
tube defect is spina bifida. Amniocentesis is weeks' gestation .
occasionally used late in pregnancy to assess whether
the baby 's lungs are mature enough for the baby to Diagnostic Testing for Trisomy 18
breathe on his own. Amniocentesis also provides
access to DNA for paternity testing prior to delivery. Ultrasonographic evaluation of trisomy 18;The
DNA is collected from the potential father and is sonographic finding of increased nuchal translucency
compared to DNA obtained from the baby during appears to be a prominent phenotypic manifestation of
amniocentesis . The results are accurate (99%) for double trisomy in the first trimester.
determining paternity . Other abnormal findings, namely subcutaneous
edema, omphalocele, and a large atrioventricular septa!
The Cordocentesis test looks for : defect. These sonographic findings were initially
The procedure is similar to amniocentesis except the considered highly suggestive of trisomy 18.
objective is to retrieve blood from the fetus versus
a mniotic fluid .Cordocentesis detects chromosome Diagnostic Testing for Trisomy 9
abnormalities (i.e. Down syndrome) and blood
disorders ( i.e. fetal hemolytic disease) . Detection of trisomy 9; trisomy 9 can be detected
Cordocentesis may be performed to help d iagnose prenatally with chorionic villus sampling and
any of the following concerns: Cordocentesis, and can be suggested by obstetric
• Malformations of the fetus ultrasonography
• Fetal infection ( i.e. toxoplasmosis or rubella)
• Fetal platelet count in the mother Diagnostic Testing for Turner's Syndrome
• Fetal anemia Ultrasonographic Analysis for Turner's Syndrome
• Isoimmunization
This test is different from amniocentesis in that it The first time presented for uterine ultra-sonography
does not allow testing for neural tube defects. 15 weeks from the date of last menstrual period . The
fetus has a posterior cervical mass, typical of the cystic
Prenatal Screening for Down Syndrome hygroma of Turner's syndrome, as well as generalized
edema and protruding abdomen with ascites and a
Genetic screens are often performed on pregnant single horseshoe kidney .
women older than 30 or 35. Common screening A mass in the posterior nuchal region detected by
procedures for Down syndrome are (Table 40 .3) : ultra- sonography is likely an encephalocele or a
• Fetal nucleated red blood cells test for trisomy meningocele .
13.

• • -
Screen Gestation periods Detection False Description
in weeks rate positive rate
Triple screen 15-20 75 percent 8.5 percent AFP and abnormal levels of hCG (human
chorionic gonadotropins) and estriol may indicate
that the developing baby has Trisomy 21 (Down
syndrome) , Trisomy 18 (Edwards Syndrome) or
another type of chromosome abnormality
Quad screen 15-20 79 percent 7.5 percent Same as above
APF/ 13-22 80 percent 2.8 percent This test measures the alfa fetoprotein , produced
by the fetus and free beta hcg, Produced by placenta .
Nuchal translucency 10-13.5 91 percent 5 percent Uses ultra sound to measures nuchal translucency
in addition to the free beta HCG and pregnancy
associated plasma proteins .
 Prenatal Trimester Screening for Turner's Syndrome 3. Epstein CJ. "Down's syndrome ; Critical genes in a
A 45, X karyotype is confirmed by fibroblast culture critical region" . Nature 2006 ;441(7093) :582-3.
and, as is frequently observed, the a-fetoprotein level 4. Lewis R. Human Genetics: Concepts and Applications ,
6th Ed . McGraw Hill , New York 2005.
in amniotic fluid drawn at the time of termination
5. Mayoclinic Complete book of Pregnancy and Baby's First
was abnormally high . Year. Johnson , Robert V, MD et al "Chap. 11 (Ultrasound
, Chorionic villus sampling), Chap. 6 (Triple Screen)".
BIBLIOGRAPHY 6. Pediatric Dentist as a Amateur Geneticist; Pediatric Dent
2005;27:146-9 .
1. Bowles BB , et al. The future of genetic counseling : 7. Stipoljev F, et al. ';.\ntenatal detection of mosaic - Trisomy
An international perspective . Nat Genetics 1999;22(2) : I by ultrasound : A case report and literature review." J
133-7. . Maternal Fetal Neonatal - Medi 2003;14(1) ;65-9.
2. Chen MD, et al. "Introduction to Trisomy 18." E 8. Williams Obstetrics Twenty-Second Ed. Gnningham ,
Medicine . Chap. 13 (Amniocentesis) .
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