P02.002 Family history of possible genetic disorder

Family history is a valuable tool in clinical genetics. It helps identify patterns of inheritance and the risk of genetic disorders. A detailed family history can reveal clues about the presence of genetic diseases and guide further investigations.

Key Components of Family History

1. Patient’s Personal History

• Current health status
• Past medical history
• Developmental milestones (in children)

2. Three-Generation Pedigree

• First-degree relatives: Parents, siblings, children
• Second-degree relatives: Grandparents, aunts, uncles, nieces, nephews, half-siblings
• Third-degree relatives: First cousins

3. Information to Collect

• Age and health status or age at death and cause of death for each family member
• Presence of chronic illnesses or genetic conditions
• History of miscarriages, stillbirths, or congenital anomalies
• Ethnic background, as some genetic conditions are more prevalent in specific populations
• Consanguinity (marriage between relatives)

4. Red Flags in Family History

• Multiple affected family members with the same or related disorders
• Early onset of disease (e.g., cancer before age 50)
• Disease in the less commonly affected sex (e.g., breast cancer in a male)
• Multifocal or bilateral occurrence of disease
• Unusual presentations of common conditions

Common Patterns of Inheritance

1. Autosomal Dominant

• Examples: Huntington’s disease, Marfan syndrome
• Characteristics: One affected parent, 50% chance of passing the disorder to offspring, often seen in multiple generations

2. Autosomal Recessive

• Examples: Cystic fibrosis, sickle cell anemia
• Characteristics: Both parents are carriers, 25% chance of an affected child, often seen in one generation

3. X-Linked Recessive

• Examples: Hemophilia, Duchenne muscular dystrophy
• Characteristics: Affects mainly males, females are carriers, no male-to-male transmission

4. Mitochondrial Inheritance

• Examples: Leber’s hereditary optic neuropathy
• Characteristics: Inherited from the mother only, affects both males and females

Case Study Example

Scenario:

A 32-year-old woman presents with concerns about her risk for breast cancer. Her mother was diagnosed with breast cancer at age 45, and her maternal aunt died from ovarian cancer at age 50.

Pedigree Analysis:

• First-degree relatives: Mother (breast cancer at 45)
• Second-degree relatives: Maternal aunt (ovarian cancer at 50)
• Potential genetic syndrome: BRCA1/BRCA2 mutation

Management:

• Genetic counseling: Discuss the possibility of hereditary breast and ovarian cancer syndrome
• Genetic testing: Consider testing for BRCA1/BRCA2 mutations
• Surveillance: Increased screening (e.g., mammography, MRI)
• Risk-reducing strategies: Prophylactic surgeries, chemoprevention

Points to Remember

1. Detailed History: Always collect a comprehensive three-generation family history.
2. Identify Patterns: Look for red flags and patterns of inheritance.
3. Counseling: Provide genetic counseling to patients and their families.
4. Testing: Recommend genetic testing when appropriate, based on family history.
5. Preventive Measures: Implement increased surveillance and preventive strategies for at-risk individuals.
6. Ethnic Considerations: Be aware of the increased prevalence of certain genetic disorders in specific ethnic groups.
7. Confidentiality: Maintain confidentiality and sensitivity when discussing genetic information.

Bibliography

1. Bennett, R.L., Steinhaus, K.A., Uhrich, S.B., O’Sullivan, C.K., Resta, R.G., Lochner-Doyle, D., Markel, D.S., Vincent, V., & Hamanishi, J. (1995). Recommendations for standardized human pedigree nomenclature. American Journal of Human Genetics, 56(3), 745-752.
2. Guttmacher, A.E., Collins, F.S., & Carmona, R.H. (2004). The family history—more important than ever. New England Journal of Medicine, 351(22), 2333-2336.
3. McKusick, V.A. (2007). Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders. Johns Hopkins University Press.
4. National Society of Genetic Counselors. (2013). Genetic counseling practice analysis. Journal of Genetic Counseling, 22(5), 662-671.