Basics
Description
- Rapid advances in elucidating the genetic basis of disease have resulted in the need for both primary care and specialty physicians to perform genetic risk assessment in their practices and refer patients for genetic counseling when indicated.
- Genetic counseling is the process of communicating information about genetic risks. It focuses on susceptibility to disease in individuals who are (1)
- Suspected of having a heritable disease
- At risk due to family history
- Concerned about affected offspring due to family history, age, or ethnicity
- Genetic counseling is provided in a nondirective manner, free of bias and coercion, thus empowering individuals or families to make well-informed decisions about their health care (1).
- Genetic screening is performed on a population of individuals potentially at risk for the condition under consideration. Definitive diagnostic testing or confirmation follows a positive or indeterminate result. Individuals who have been identified by screening may receive genetic counseling to explain the implications of a positive screening result and the need for further diagnostic testing.
- Counselors may assist clinicians and patients in choosing appropriate screening or diagnostic tests.
- Pregnancy considerations: Genetic counseling may address elevated genetic risks associated with maternal age, family history of heritable genetic disease, teratogenic exposures, prenatal screening results suggestive of increased risk, or abnormal findings on prenatal ultrasound.
- Newborn screening: Varies by state according to the genetic makeup of the population. Conditions screened are those for which there is an effective treatment that can make a clinically significant difference.
- Pediatric considerations: Genetic counselors work with pediatric medical geneticists to evaluate children at risk for a chromosomal abnormality or genetic syndrome because of developmental delays, intellectual disabilities, certain medical problems, and/or dysmorphic features. Children should not be tested for adult-onset conditions for which there is no treatment in childhood.
- Geriatric considerations: Genetic counseling and screening may be indicated to assess genetic predisposition for individuals and family members for conditions common in elderly populations.
Epidemiology
Incidence
Recognizable genetic disease will be diagnosed in 3-7% of the population at some point during their lifetime. �
Prevalence
- Chronic medical illnesses such as diabetes, heart disease, cancer, and Alzheimer disease have a genetic basis in up to 10% of cases.
- 50% of pediatric hospital deaths are associated with genetic diseases.
- Congenital malformations are identified in 2-5% of newborns.
Etiology and Pathophysiology
Genetic disorders are classified into four major etiologies: �
- Chromosomal disorders
- Single gene disorders
- Multifactorial disorders
- Mitochondrial disorders
Genetics
- Patterns of transmission include the following:
- Autosomal recessive
- Autosomal dominant
- X-linked
- Mitochondrial/maternal
- De novo mutations, incomplete penetrance, and variable expressivity may obscure the nature of inheritance, which can lead to variable presentations of many conditions.
Risk Factors
- Identification of genetic risk may allow tailored interventions, lifestyle changes, and disease-prevention strategies (1).
- Family history of genetic disease
- Consanguinity
- Ethnic or racial background (see "Diagnostic Tests & Interpretation"�)
- Abnormal pregnancy screening tests
- Aneuploidy screening
- Abnormal ultrasound results
- Abnormal screening results for cystic fibrosis, Jewish-inherited genetic disease, or other positive carrier screening
General Prevention
Genetic conditions cannot be prevented under ordinary circumstances (preimplantation diagnosis or prenatal diagnosis and pregnancy termination may be possible when a specific risk is known); however, diet or behavior can be modified to ameliorate some conditions (e.g., phenylketonuria and dietary modification). �
Diagnosis
History
- The content of genetic counseling include the following:
- Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence.
- Third-generation pedigree is an important component.
- Education about inheritance, testing, management, prevention, resources, and research
- Counseling to promote informed choices and adaptation to the risk or condition
- All counseling is done in a nondirective fashion, free of any coercion or bias.
- Pregnancy considerations: Genetic counseling is an integral component of prenatal care and is optimally performed prior to conception or early in pregnancy (1)[B].
Physical Exam
Genetics counselors do not usually perform physical examinations; however, medical geneticists may perform examinations seeking physical signs suggestive of a particular condition or gene that would predispose the patient or offspring to genetic disease. �
Differential Diagnosis
Genetic counseling and screening help to formulate a differential diagnosis, inform the need for further testing modalities, and arrive at an accurate diagnosis and prognosis. �
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
- Genetic testing for adult-onset conditions is performed to confirm or establish a diagnosis or to assess/predict risk for asymptomatic patients.
- Genetic testing can be performed at many different times (2,3,4,5,6,7):
- Preimplantation
- Prenatal
- Carrier testing
- Diagnostic: A particular condition is clinically suspected.
- Predictive: Asymptomatic individual is at risk. Predictive testing is not performed on children for adult-onset diseases.
- Genetic screening based on ethnicity:
- Hemoglobin electrophoresis: sickle cell disease (African), thalassemia (Mediterranean), congenital hemoglobinopathies (Asian, Mediterranean, African)
- Cystic fibrosis (Central-Northern Europeans)
- Ashkenazi Jewish genetic diseases
- Prenatal screening
- 1st trimester: serum analytes plus nuchal translucency
- 1st and 2nd trimesters: serum analytes plus nuchal translucency plus 2nd-trimester serum analytes
- 2nd trimester: quad screen, serum analytes
- Genetic screening in infertility
- Chromosome analysis
- Hereditary thrombophilia (e.g., factor V Leiden)
- Cystic fibrosis
- Pediatric considerations
- Newborn screening is state mandated to screen for at least 29 conditions, which allows for early treatment and may prevent death or disability (8). Pediatric geneticists may order specific genetic tests to identify the underlying cause of a child's congenital anomalies, intellectual disabilities, and/or dysmorphic features.
- Adult/geriatric considerations
- Adult-onset genetic conditions (e.g., cardiomyopathies, Huntington disease)
- Cancer-specific testing
- Based on personal or family history
- BRCA1/BRCA2: breast/ovarian cancer
- Hereditary cancer panels
- Some genetic cancers occur in children.
Follow-up tests & special considerations
- Circulating cell-free fetal DNA analysis is a rapidly emerging, sensitive technique that detects major aneuploidies during pregnancy. Many patients opt for cell-free fetal DNA analysis in lieu of invasive prenatal testing.
- Imaging modalities such as ultrasound (especially prenatally), MRI, and CT scan are often used to gain further diagnostic information and provide a more accurate diagnosis in prenatal, pediatric, and adult populations.
Diagnostic Procedures/Other
- Prenatal diagnostic testing (2)[B] consists of chorionic villus sampling (CVS), genetic amniocentesis, and/or fetal blood or tissue sampling.
- Chromosomal microarray studies may be beneficial when standard karyotyping is normal but prenatal ultrasound or pediatric phenotypic findings suggest a genetic etiology (4)[B].
- Venipuncture for a blood sample is often performed for the affected individual and family members to determine the presence or absence of specific disease causing gene alterations.
- Pediatric considerations: skin or muscle biopsy in certain cases for diagnosis and to direct genetic testing
- Adult/geriatric/cancer considerations: Genetic testing may be performed directly on the cancerous tissue to direct additional testing and/or tailor treatment.
Test Interpretation
Interpret within the context of screening versus diagnostic testing. Some results may have unknown significance, especially with microarray testing. �
Treatment
General Measures
- Following diagnosis of a particular condition, genetic counseling allows discussion of presently available treatment options and facilitates further medical or surgical care by other involved clinicians.
- Pregnancy considerations: invasive diagnostic testing (CVS, amniocentesis), fetal therapy (medical, in utero surgery), pregnancy termination
- Pediatric considerations: A diagnosis of a specific genetic condition can direct management and surveillance.
- Adult/geriatric considerations: Increased surveillance can lead to early detection of cancer in individuals with a genetic predisposition.
Medication
First Line
- Medical therapy in pregnancy must balance risks and benefits of in utero exposure.
- Use of genetic test results to guide treatment is most common in oncology. Cancer genetics may direct chemotherapy choice.
Issues for Referral
The detection of a genetic or nongenetic condition may warrant referral to specialist clinicians for further evaluation and treatment. �
Additional Therapies
N/A �
Surgery/Other Procedures
- In utero surgery now available for fetal repair of several conditions (e.g., spina bifida)
- High-risk individuals may choose surgery to decrease risk of future disease (e.g., mastectomy or oophorectomy to decrease risk of breast or ovarian cancer with BRCA mutation).
Complementary & Alternative Therapies
This has become popular among families affected by genetic conditions, although usefulness is not well established. �
Inpatient Considerations
Admission Criteria/Initial Stabilization
If a condition is suspected to have a genetic etiologic component, genetic counseling can be requested to assist with diagnosis or treatment choices. �
Ongoing Care
Follow-up Recommendations
- All genetic counseling sessions should result in generation of a formal report to the referring physician, describing the indications for counseling, risk assessment, and any recommended testing or other interventions.
- All genetic screening results should be communicated to all involved clinicians and to the patient/family.
- The genetic counselor should serve as an ongoing source of information and support to the patient and family.
Diet
- Pregnancy considerations: Periconceptional folic acid reduces the occurrence of open neural tube defects by 50% in the general population and by 70% in families with affected offspring.
- Some metabolic diseases are treated primarily with diet.
Patient Education
The genetic counselor provides extensive patient education. �
Prognosis
Variable based on condition �
Complications
Decision making can be difficult and affect family and emotional relationships, reproductive decisions, and paternity assessment. �
References
1.American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 478: family history as a risk assessment tool. Obstet Gynecol. 2011;117(3):747-750. �
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2.American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 88, December 2007: invasive prenatal testing for aneuploidy. Obstet Gynecol. 2007;110(6):1459-1467. �
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3.ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007;109(1):217-227. �
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4.American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013;122(6):1374-1377. �
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5.American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 486: update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011;117(4):1028-1031. �
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6.ACOG Committee on Genetics. Committee Opinion No. 442: preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol. 2009;114(4):950-953. �
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7.American College of Obstetricians and Gynecologists Committee on Opinion. Committee Opinion No. 430: preimplantation genetic screening for aneuploidy. Obstet Gynecol. 2009;113(3):766-767. �
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8.American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 481: newborn screening. Obstet Gynecol. 2011;117(3):762-765. �
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Codes
ICD09
- V26.33 Genetic counseling
- V82.79 Other genetic screening
- V18.9 Family history of genetic disease carrier
- V84.89 Genetic susceptibility to other disease
ICD10
- Z31.5 Encounter for genetic counseling
- Z13.79 Encounter for other screening for genetic and chromosomal anomalies
- Z84.81 Family history of carrier of genetic disease
- Z31.430 Encounter of female for testing for genetic disease carrier status for procreative management
- Z31.438 Encounter for other genetic testing of female for procreative management
- Z31.44 Encounter for genetic testing of male for procreative management
- Z31.440 Encounter of male for testing for genetic disease carrier status for procreative management
- Z31.448 Encounter for other genetic testing of male for procreative management
SNOMED
- 79841006 genetic counseling (procedure)
- 47461006 Genetic disorder carrier (finding)
- 429962007 Family history of hereditary disease (situation)
- 430695000 Family history of genetic disorder carrier (situation)
- 32895009 Hereditary disease (disorder)
- 473200002 genetic screening for disorder (procedure)
Clinical Pearls
- Patient autonomy is the central tenet in genetic counseling, and assuring that the patient has sufficient support to make decisions is vital.
- There is general agreement that children should not be tested for adult-onset diseases for which there are no effective treatment in childhood.
- Genetic testing should be coordinated through a genetic counselor to assure appropriate testing, interpretation, and follow-up.