Pathophysiology Of Genetics And Genetic Testing Discussion

I’m working on a Nursing question and need guidance to help me study.

Based on what you have studied and heard in class, the impact on genetics on disease is becoming a part of how we practice.  If you watch television, you might have seen the advertisements for genetic testing and you often see people very excited about “finally” having detailed information about their heritage.  I want to start a discussion on the pros and cons of genetic testing. By genetic testing, I do not mean heritage, but instead the effects of genetics on ones’ health.  Currently, patients can be tested for a number of issues, like hemophilia or sickle cell disease, but the horizon is full of possible testing, including looking at the risk of cancers and problems with the fetus.   This is a personal opinion and you can bring in resources if you like, but I’d like you to discuss genetic testing because, as a nurse, people will ask your opinion and you cannot really give an honest response until you explore it.  A couple of possible starting points:
Should it be mandatory?  Should doctors, insurance companies, hospitals, employers require it of everyone they see, insure, hire, treat?
What are the benefits of genetic testing?
What are the potential problems with genetic testing?
If it was offered to you today, would you do it?
How do you feel about companies like “23 and Me” that advertise on television? Do you think this testing is accurate and could be used to make health-care decisions? Pathophysiology Of Genetics And Genetic Testing Discussion

ORDER YOUR PAPER HERE

Introductory Concepts a nd Clinica l P ers pectives by Theres a Ca priotti a nd J oa n P a rker F rizzell Chapter 3 Copyrig ht © 2016 F .A. Da vis Compa ny Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell   Genomics is the study of the multiple genes of an organism and their interactions. Pharmacogenomics is the study of how genes influence an individual’s response to medications. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Double-helical structure composed of nucleotides Nucleotide = pentose sugar, phosphate, purine or pyrimidine nitrogen base Nitrogen bases = adenine, thymine, guanine, cytosine ( A-T C-G) Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     DNA synthesizes RNA within the nucleus. RNA = mirror image of a DNA strand RNA = one strand RNA nitrogen bases = adenine-uracil cytosineguanine Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Specific group of nucleotides of the DNA helix that carry a code for a protein Protein coding sequences = exons Sequences with no code = intron Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      An average gene contains 3,000 nucleotide base pairs. Within a gene, an arrangement of three specific nucleotide bases = codon. Codon contains directions for synthesis of a specific amino acid. An average gene can code for 1,000 amino acids. Example: adenine-thymine-guanine = methionine Copyright © 2016 F.A. Davis Company Pathophysiology: Pathophysiology Of Genetics And Genetic Testing Discussion

Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     Single nucleotide polymorphism (SNP) (called a point mutation) Defective gene (eg, BRCA1, BRCA2) Defective whole chromosome (eg, trisomy 21) Germ cell mutation = mutated gamete Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Mutations can be inherited or sporadic (environmentally induced). Somatic cell mutation is not inherited. Germ cell mutation can be inherited. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Labeling a gene: chromosome #, long arm (q) or short arm (p), region Genes are sometimes given “nicknames” such as BRCA gene, which means breast cancer gene. Example: Cystic fibrosis gene; 7q31.2 indicates the gene is found on the long arm of chromosome 7 in the region numbered 31.2; nickname is CFTR gene. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Appearance and number of chromosomes of an individual Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      23 pairs of chromatids= 46 chromosomes 22 pairs are somatic cell chromosomes (called autosomes). 23rd pair includes the sex chromosome. Structure = two chromatid strands connected by a centromere Corresponding genes on each chromatid = an allele Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell   In a homozygous individual, both alleles on each corresponding chromosome are the same. In a heterozygous individual, the alleles on corresponding chromosomes are not the same. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  An allele can carry a dominant trait or a recessive trait (eg, brown eyes = dominant and blue eyes = recessive). Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell   Phenotype: how the gene mix is manifested in the individual Genotype: the genetic makeup of a person (eg, a brown-eyed person can have a B-B or B-b genotype) Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell A female often carries a trait that the male offspring expresses.  The Y chromosome does not have an equal number of genes as the X chromosome. Some genes on the X chromosome are unopposed by an allele on the Y. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     Penetrance: ratio of how many persons with the phenotype have the genotype. Example: A gene is highly penetrant if most people express a gene if they have it; for example, if a woman has the BRCA gene, there is an 85% chance of getting breast cancer; this gene is highly penetrant. Expressivity: A disorder can be expressed more or less severely in different individuals. Example: A person may have a gene for familial hypercholesterolemia but can have a mild or severe form of the disease. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell   A disease is caused by a combination of inherited susceptibility and environmental factors that trigger a disorder. Diabetes or cancer is a multifactorial genetic disease; a genetic susceptibility and environmental trigger cause this disorder Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    A mutation in one nucleotide of a gene sequence Nucleotide = pentose sugar, phosphate, purine, or pyrimidine nitrogen base Example: Pathophysiology Of Genetics And Genetic Testing Discussion

A normal nucleotide sequence may be ACTTG…but in the disease the nucleotide sequence is…ACTGG. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      Mitochondria have their own ribosomes and DNA that regulate energy production. They are theorized to be independent, bacterialike organisms that became incorporated into human cells. During fertilization, the ovum destroys the sperm mitochondria. All mitochondria DNA is derived from the mother. Maternity tests can be based on mitochondrial DNA. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    DNA alterations or mutations are changes in nucleotide sequences, as well as deletions or insertions of nucleotides. These changes can represent the change of base sequences in a codon, leading to a change in the protein structure. For example, a nucleotide base substitution results in a different amino acid being included in hemoglobin formation, leading to the development of sickle cell anemia. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     Activated oncogenes can be inherited or acquired. When the cell that possesses this activated oncogene undergoes transcription, the RNA will carry the defective message of the activated oncogene onto the ribosomes. The ribosomes, in turn, will synthesize defective proteins called oncoproteins. These oncoproteins will direct the cell to undergo uncontrolled proliferation, persistent mitotic divisions, or persistent cancerous growth, which is why activated oncogenes can be considered cancercausing genes. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  These genes inhibit uncontrolled cellular mitosis and lead to persistent proliferation. An example is the p53 tumor suppressor gene, which stops the mitotic cell division cycle. When defective, tumor suppressor genes do not suppress cancerous transformation of cells and cancer growth occurs uninhibited. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Another way that cancer occurs is through viral insertion of an oncogene. For example, the human papilloma virus (HPV) inserts its DNA into the DNA of cervix cells. When activated, this DNA stimulates the abnormal growth cycle associated with cancer cells. Additionally, it inhibits the action of p53, a tumor suppressor gene. This is the mechanism for the development of cervical cancer from HPV infection. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  Pairs of alleles make up an individual’s genotype. If one of the alleles of a pair becomes damaged or mutated, the normal corresponding allele can counteract the effect in most cases. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  According to Knudson, the initial allelic mutation is the “first hit” in his theory. In his investigations, he noted that cancer only developed in persons who acquired a second allelic mutation. Persons who developed cancer possessed a hereditary mutation on one allele and acquired a second mutation on their normal allele sometime in the course of their lifetime… “two hits.” Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  Abnormal number of chromosomes  Example: trisomy 21 Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  When one part of a chromosome breaks off and connects to another chromosome Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  Occurs when there are cells with different numbers of chromosomes within the same individual Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  Acquired genetic alterations, inherited disorders, and infectious disease can be detected by: ◦ Polymerase chain reaction (PCR) ◦ Fluorescence in situ hybridization (FISH) ◦ Southern blotting Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     Chorionic villus sampling (CVS) 10 to 12 weeks Amniocentesis 16 to 18 weeks Ultrasound Percutaneous umbilical cord blood sampling (PUBS) Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell        Women 35 years or older who are pregnant or are planning to become pregnant Abnormal ultrasound findings Couples who are close blood relatives, such as first cousins Women who have a condition, such as diabetes, that can be associated with an increased risk of fetal problems Ethnicity Unexplained or multiple miscarriages Family history of an inherited condition, intellectual disability, or birth defects Copyright © 2016 F.A. Davis Company Pathophysiology: Pathophysiology Of Genetics And Genetic Testing Discussion

ORDER YOUR PAPER HERE

Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Proteins that are produced by the developing placenta and fetus enter the mother’s blood:  AFP (alpha-fetoprotein)  hCG (human chorionic gonadotropin)  uE3 (unconjugated estriol)  DIA (dimeric inhibin A) If a maternal serum screening test is positive, it indicates an increased chance for a fetal problem. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Viral vector Liposome Artificial chromosome under investigation Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell         Absent or dysfunctional LDL receptors Mutation at 19p gene locus Normally uptake of LDL by liver LDL receptors Liver lacks LDL receptors so liver does not have uptake of LDL and cholesterol manufacture is not suppressed. Homozygous form of disease; severe total cholesterol levels 600 to 1,000 mg/dL Heterozygous form of disease; less severe; total cholesterol 200 to 400 mg/dL Early arteriosclerosis develops; early angina and MI Xanthoma and xanthelasma Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      Autosomal dominant condition Individual is born with APC allele and needs to have other allele mutate in order to develop disease. Early onset of hundreds to thousands of adenomatous polyps throughout the colon Mutation at 5q21 = APC gene (defective tumor suppressor gene) High risk of colon cancer Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     Autosomal dominant disorder Connective tissue disorder Mutations in the fibrillin-1 (FBN1) gene on chromosome 15 Abnormalities exist in the structural components of the aorta and heart valves, airways of the lung, suspensory ligament of the lens, dura mater of the spinal cord, and other connective tissues of the body. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell             Most common in males Tall stature with elongated arms and fingers Kyphoscoliosis Ligament hypermobility of the hips, knees, ankles, arches, wrists, and fingers Heart murmur from aortic regurgitation or mitral prolapse Dysrhythmia Aortic dissection Burning sensation and numbness or weakness in the legs because of dura mater defects Joint pain (adult patients) Dyspnea, severe palpitations, and substernal pain in severe pectus excavatum Spontaneous pneumothorax Visual problems Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell        Autosomal dominant Mutated NF1 gene (tumor suppressor gene) Mutated NP2 gene Mutated 17q and 22q Gene that codes for the proteins neurofibromin and merlin are mutated Decreased production of these proteins results in various clinical features “Elephant man” syndrome Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell  The clinical criteria used to diagnose NF are as follows: ◦ Six or more café-au-lait spots (hyperpigmented macules) ◦ Two or more typical neurofibromas or one large neurofibroma ◦ Spinal cord and meningeal tumors ◦ Optic and acoustic nerve tumor ◦ Two or more tumors in the iris (Lisch nodules), often only identified by an ophthalmologist ◦ Long-bone abnormalities ◦ First-degree relative (eg, mother, father, sister, brother) with NF1 ◦ Scoliosis ◦ Bowed legs ◦ Macrocephaly Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     Abnormalities in the synthesis of collagen and other connective tissue proteins Skin is highly elastic and joints are hypermobile. Easy bruising, poor wound healing, mitral valve prolapse (MVP), arterial aneurysms, arterial dissections, and occlusions The classic form of EDS occurs because of a mutation on the 9q34.2 and 9q34.3 genes, also called the COL3A1 and COL3A2 genes. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      Autosomal recessive disease caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR gene encodes for a protein that functions as a chloride channel and also regulates the flow of other ions across the surface of epithelial cells. The CFTR gene locus is 7q31. CF chiefly involves the respiratory system and pancreas. Thick mucous secretions form and block the lungs and pancreas. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell   Lysosomal storage diseases are classified according to the accumulated substances, which include the sphingolipidoses, oligosaccharidoses, mucolipidoses, mucopolysaccharidoses (MPSs), lipoprotein storage disorders, lysosomal transport defects, and others. Each lysosomal storage disease presents differently according to the undigested substance that accumulates within the cells and according to which major organ is affected. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      Lysosomal storage disease Mutation on chromosome 15 Deficiency of lysosomal enzyme: hexosaminidase A Ashkenazi Jews Ganglioside accumulates in the cells, particularly the central nervous system, causing progressive destruction of neurons and brain cells. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      Infants born with Tay Sachs disease appear normal until approximately 6 months of age. As the infant matures, motor incoordination, lethargy, muscle flaccidity, and increasing cognitive impairment become apparent. A characteristic that is diagnostic of Tay Sachs disease is a “cherry red spot” seen on the retina on ophthalmological examination. Death usually occurs by age 3 years. Prenatal diagnosis and carrier detection of Tay Sachs disease is possible. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell   Niemann-Pick disease Gaucher disease Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      Abnormal copper metabolism Liver damage; cirrhosis Organs develop copper deposits Kayser-Fleischer rings visible in the eye Early symptoms include tremor, difficulty speaking, excessive salivation, ataxia, masklike faces, clumsiness with the hands, and personality changes. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell      Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder. It is an X-linked inherited disease that primarily affects men. RBCs undergo hemolysis under stresses Symptoms: jaundice, yellowing of the skin and sclera Diagnosis: Heinz bodies, bite cells Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell     Males have a 47XXY karyotype. Lack of development of the testes, gynecomastia, and skeletal and cardiovascular abnormalities occur. Intellectual impairment also occurs. Testosterone deficiency causes tall, lanky body proportions; sparse or absent facial, axillary, and pubic hair; decreased muscle mass and strength; feminine distribution of adipose tissue; decreased physical endurance; and osteoporosis. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Missing X chromosome in the female so that karyotype is 45X Webbed neck, short stature, infertility, broad shield-shaped chest, small hips Cardiovascular problems, ovarian failure, hypothyroidism, visual problems Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell   Second most common cause of genetically associated mental deficiencies after trisomy 21 Defective Xq27.3 gene (also called the familial mental retardation [FMR] 1 gene) Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell            Autistic behavior Hand flapping and avoidance of eye contact Shyness, sensory integration difficulties, attention deficits, hyperactivity, impulsivity Depressed affect Anxiety Learning disabilities Aggressive tendencies Mitral valve prolapse Scoliosis Craniofacial, genital, and musculoskeletal abnormalities Males have a long face with large mandible, large everted ears, and large testicles; hypermobile joints, high arched palate. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Trisomy 21 Diagnosed prenatally with amniocentesis, PUBS, CVS, and extraction of fetal cells from the maternal circulation 1 in 50 births to mothers older than 45 years Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell         Flat facial profile Eyes oblique; palpebral fissures Epicanthic folds 80% of children have an IQ of 25 to 50. The remaining 20% have normal or near normal intelligence. 40% of children have congenital heart disease and esophageal and intestinal malformation. 10- to 20-fold increased risk of developing leukemia Weak immune system; susceptible to infection Adults susceptible to early Alzheimer’s disease Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell              Also called Angelman syndrome Deletion or disruption of genes in the proximal arm of chromosome 15 Hypothalamic dysfunction Severe obesity; constant hunger caused by dysfunction of the hypothalmus Hypotonia Low IQ Short stature Hypogonadotropic hypogonadism Strabismus Small hands and feet Ataxic gait Behavioral problems Seizures Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell    Adult-onset, autosomal-dominant inherited disorder associated with degeneration of specific neurons in the basal ganglia and cortex Genetic defect at 4p16.3 called the Huntington gene (also called HTT or HD gene) The gene defect causes a part of DNA, called a CAG repeat sequence, to repeat many more times than it should and form the Huntington protein. Copyright © 2016 F.A. Davis Company Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell         Patients commonly develop symptoms in their mid-30s and 40s. Chorea = movement disorder seen in HD Initially, mild chorea causes dancelike movements or tics. Severe chorea occurs later and can cause uncontrollable flailing of the extremities, termed ballism. As the disease progresses, chorea is replaced by parkinsonian features, such as slowed up movements, muscle rigidity, and postural instability. In advanced disease, patients develop an akinetic-rigid syndrome, without movement at all. Other late features are spasticity, dysarthria, dysphagia, and slowed cognition to dementia, which occurs gradually. Severe depression and suicidal ideation is common. Copyright © 2016 F.A. Davis Company National Genetics Education and Development Centre Taking and Drawing a Family History Ralph 1932 d. heart attack Beatrice 1932 3 Rachel 21/7/1952 type 2 diabetes Edward 18/11/1958 obese George 10/2/1955 Lily 9/1/1980 open wound on L foot Maureen 4/3/1958 Nick 23/11/1982 Sharon 30/6/1984 Supporting Genetics Education for Health www.geneticseducation.nhs.uk Project Team Professor Peter Farndon Ms Michelle Madeley NHS National Genetics Education and Development Centre Ms Erin Harvey NCHPEG (National Coalition for Health Professional Education in Genetics) © 2008 NHS National Genetics Education and Development Centre This publication may be photocopied for non-commercial purposes for healthcare staff. First published 2008 Birmingham: NHS National Genetics Education and Development Centre ISBN 978-0-9556680-5-0 Copies available from: The NHS National Genetics Education and Development Centre Morris House c/o Birmingham Women’s NHS Foundation Trust Edgbaston Birmingham B15 2TG Phone: 0121 623 6987 www.geneticseducation.nhs.uk Taking and Drawing a Family History Series National Genetics Education and Development Centre Introduction This pack of factsheets about collecting and recording a genetic family history is one of a series of resources developed by the NHS National Genetics Education and Development Centre to support health professionals in undertaking genetic activities in clinical practice. This sheet may be photocopied for non-commercial education purposes for healthcare staff and you are welcome to use the pack or individual sheets to share with colleagues or to use within your teaching. The series can be downloaded from our website www.geneticseducation.nhs.uk along with a range of other support material. Further series of factsheets sheet eets ets on o understand understanding e diing g mo m modes of inheritance and interpreting nterpret terpreting family m pattern patterns ns of m medical conditions are in preparation. Contents include: Part 1: Part 2: Part 3: Part 4: Part 5: Part 6: Part 7: Part 8: Ralph 1932 d. heart attack Key points for taking and d drawing a genetic family history What is a genetic family history?

s Why is taking a genetic family m history important? What are the accepted symbols m to use in drawing a pedigree? What and how much information m should be included in a pedigree? Gathering information and drawing a genetic family tree Pedigree r drawing exercisess Safeguarding feguar egua u the information mation i in a genetic family milyy hi his history Test st your knowledge: a family history puzzle e Cancer ncer cer ssc scenarios Rachel 21/7/1952 type 2 diabetes Edward 18/11/1958 obese George 10/2/1955 Lily 9/1/1980 open wound on L foot 3 Maureen 4/3/1958 Nick 23/11/1982 This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Beatrice 1932 Sharon 30/6/1984 Supporting Genetics Education for Health www.geneticseducation.nhs.uk This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series: Part 1 National Genetics Education and Development Centre Key points for taking and drawing a genetic family history Taking and drawing a genetic family history may involve asking for information on many members of a family, or may be targeted to detect a family pattern of a particular condition, according to the clinical question. The basic approach is the same – collecting information about relatives and their partnerships in one generation before moving up or down a generation. This factsheet is a summary of our series on “Taking and drawing a family history” which offers more information and detailed explanations. The series includes, for example, factsheets on how to decide what and how much information is needed, the questions to ask and how to build up a detailed pedigree step by step. It is important to be sensitive when asking questions about illnesses and relationships in the family. Key questions about family members Although it may be best to take a systematic approach to enquiring about each branch of a family, sometimes this may not be possible in a busy clinic. There are some useful general questions, however, to gain a quick overview of medical conditions in a family. Answers to these questions may trigger a need for drawing out how the people with the condition are related to each other, to inform a preliminary assessment of whether there is an increased genetic risk which warrants further investigation or specialist referral. Key questions • “Do you have any concerns about diseases or conditions that seem to run on either your or your partner’s side of the family?” • “Does anyone have a major medical, physical or mental problem?” • “Has anyone ever needed treatment in hospital? Has anyone ever had any serious illnesses or operations? How old were they at diagnosis?” (Avoid just asking “Is everyone well?” as past medical history may not be offered!) • “Have any adults, children or babies died? How old were they and what was the cause of death? Have there been any miscarriages or babies who were stillborn?” Each specialty will also have key questions about symptoms and signs which would alert the clinician to the possibility that a genetic condition might be present in a family. Tips for taking and recording a genetic family history On the next page we outline the key steps in taking a genetic family history. In the family shown, the people giving the information are your patient and her husband. We have highlighted the different branches of their families and numbered them. Recording details of relatives in this order works well in practice: ask about partners, children, brothers, sisters and parents, moving across and then up/down the generations. This is set out overleaf. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Steps in taking and recording a genetic family tree – branch by branch 7 Relatives of partner‛s father 11 Relatives of father Relatives of partner‛s mother Grandfather (mother‛s side) 8 10 9 Partner‛s father Your patient Uncle Aunt 3 2 Husband/partner Daughter Mother Father 1 5 6 4 Partner‛s mother Grandmother (mother‛s side) Brother Son Nephew Sister in law Niece Cousin Date on which pedigree taken Name of person taking the pedigree Fig. 1 How to record information about the family – branch by branch • Ask about your informant and his or her partner(s) and their children (Branch 1). “How many children have you had? Have you lost any children?” “Are all your children with the same partner or were any with previous partners?” • Next ask about each brother and sister of the informant (Branch 2), his or her spouse(s) and their children (Branch 3). Remember to ask if any have died, or were lost during pregnancy. • Record details about the parents of your informant (Branch 4). • Choose one of the parents (usually the mother). Record details of each of the person’s brothers and sisters (Branch 5) and their children (Branch 6). • If you need to gather inf0rmation about your patient’s grandparents (Branch 7) collect it now. • Then ask the same questions about relatives of the other parent, usually the father (Branch 8). • Now return to your informant’s partner and collect information about his/her relatives – brothers and sisters and parents (Branch 9). • If you need information about the relatives of parents of the partner, choose one – usually the mother first (Branch 10). Having collected information, then ask about the relatives of the father of the partner (Branch 11). At the end, • Thank the informant, and ask: “Is there anything else you think I should know that I haven’t asked about?” • Date and write your name legibly on the pedigree. Add an explanation of any abbreviations. • Ask for consent to share family history information with colleagues and/or other family members and note this. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series: Part 2 National Genetics Education and Development Centre What is a genetic family history? Information from a family tree can be important in making diagnoses and assisting clinical management. This series of factsheets focuses on the knowledge and skills required to take and record genetic family histories. What is a genetic family history? A genetic family history consists of information about • the biological relationships between family members and • any medical conditions they may have. Although the information can be written as text, the family history is usually recorded as a family tree (pedigree) which allows a pictorial representation of family relationships and those family members affected by medical conditions. The information is usually collected during a clinical consultation, and used to draw the family tree in the presence of the person giving the information (Fig. 1). There is international agreement that standardised pedigree symbols should be used, to ensure that health professionals throughout the world can share, understand and interpret family history information (Fig. 2). Pathophysiology Of Genetics And Genetic Testing Discussion

It is therefore useful for health professionals to be able to “read” a pedigree, even if their roles do not include taking family histories regularly. There are other ways of collecting family history information; for instance, the patient or family may agree to complete a family history form. However, most health professionals find it easier to gain an overview through visual representation in a pedigree. Fig. 1 Taking a family tree Fig. 2 Standardised pedigree symbols Other factsheets in this series This sheet is part two in the ‘Taking and Drawing a Family History Series’. All are based on clinical experience. They include: • • • • • • Why is taking a genetic family history important? What are the accepted symbols to use in drawing a pedigree? What and how much information should be included in a pedigree? Gathering information and drawing a genetic family tree. Pedigree drawing exercises. Safeguarding the information in a genetic family history. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Further support The NHS National Genetics Education and Development Centre is developing materials to support health professionals whose roles include taking and recording family history information. In addition to this toolkit, there are resources on: • different modes of inheritance • pedigree patterns associated with them • clinical information about genetic conditions likely to be met in practice. Video clips showing pedigrees being taken in practice will be available later in 2008. Resources are available free for noncommercial education purposes for healthcare staff on the Centre’s website www.geneticseducation.nhs.uk This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series: Part 3 National Genetics Education and Development Centre Why is taking a genetic family history important? With the exception of conditions resulting from accidental trauma, every disease has some genetic component. The strength of the genetic component in a family may be apparent by the number of people affected by a particular condition. This is why taking a family history is important. A positive family history can be an important risk factor for asthma, diabetes and certain forms of cancer and can identify families with known single-gene disorders. Some UK national clinical guidelines therefore highlight the importance of taking a genetic family history. If the family history is not considered, clinically meaningful information might be overlooked. In clinical management, information from the family tree can be just as important as information from a laboratory test. Arthur b. 1/2/1927 Elizabeth b. 11/7/1953 James b. 6/3/1951 Olive b. 6/11/1928 Michael b. 1928 Peter b. 7/9/1949 Debbie b. 12/4/1952 d. 3/5/1994 Died of breast cancer aged 42 Jane b. 9/7/1976 John b. 4/7/1950 Anne b. 10/10/1931 d. 6/10/1979 Died of breast cancer aged 47 Susan b. 7/11/1953 d. 5/9/1990 Died of ovarian cancer aged 36 Lynda b. 18/6/1957 This medical pedigree was taken by A. GP Date 1/9/2008 Fig. 1 Example of a family tree Some further benefits of taking a family history are highlighted below: The genetic family history can reveal patterns of inheritance Patterns of inheritance can often be easily visualised in a family in the form of a pedigree. Recognising a pattern of people with a particular condition may suggest an underlying type of inheritance. The pattern may also help to distinguish between conditions with similar presentations because they are known to have different modes of inheritance. The genetic family history may help make or refine a diagnosis Considering similar or related symptoms which occur in several members of a family may reveal that in fact they are all features of one unifying diagnosis. Understanding the variability in a family may allow earlier diagnosis in some family members, especially important if early surveillance and treatment have been shown to be of value. This applies particularly in some autosomal dominant disorders which have variable expression (such as Marfan syndrome, neurofibromatosis type 1 or forms of osteogenesis imperfecta). This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk The genetic family history helps assess the likelihood of genetic disease in relatives Genetic information is family information. If a family history is not taken, a patient’s relatives are less likely to be considered; the half brother, aunt, or pregnant cousin who may also have a genetic risk and so be prone to certain medical complications may not be identified. The genetic family history can affect testing, treatment and management strategies Family history information is needed to identify appropriate family members with a close biological relationship to the affected person so that treatment or management guidelines can be offered and implemented as appropriate. Individuals who may benefit from genetic testing may also be identified from the family history. Guidelines for investigation, management and surveillance (for instance colonoscopy or mutation analysis for inherited bowel cancer) can thus be instituted for other family members who may have been identified to be at risk. The genetic family history may highlight the need for referral for specialist opinion Where someone has been identified as being at higher risk as a result of their family history, it may be appropriate to refer the patient for specialist opinion (such as a suspected diagnosis of Marfan syndrome). Details about the pattern of disease and affected members will be valuable information for genetic and other specialists. Taking the genetic family history helps in building rapport with patients In addition to having medical benefits, eliciting genetic family history information creates opportunities for the patient and provider to develop trust, to ask questions, and to correct any misconceptions about a symptom or illness. Since the family history is easily updated to reflect births, deaths, and other major events in a family, it will also grow with time. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series: Part 4 National Genetics Education and Development Centre What are the accepted symbols to use in drawing a pedigree? Standardised symbols for drawing pedigrees have been adopted internationally. This helps to ensure that health professionals throughout the world can share, understand and interpret family history information. It is therefore useful to know about and be able to “read” a pedigree, even if a health professional’s role does not include taking family histories regularly. The pedigree symbols for individuals (Fig. 1) need to be connected together to show family relationships. Drawing lines between pedigree symbols correctly (Fig. 2) is the key to a good pedigree. Male Female Sex Unknown Marriage/partnership Individual Divorce/separation Affected individual (symbol coloured in) Where the partners are blood relatives (consanguineous relationship) Multiple individuals Children/siblings 5 5 5 line of descent sibship line individual line Deceased Pregnancy Identical twins (monozygotic) P P male female P Miscarriage Non-identical twins (dizygotic) Person providing pedigree information Fig. 1 Examples of most commonly used pedigree symbols This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Fig. 2 Examples of relationship lines Supporting Genetics Education for Health www.geneticseducation.nhs.uk Drawing a pedigree, step-by-step The following is an example of a small family to demonstrate how pedigree symbols and relationship lines are drawn. A pedigree usually contains additional information about family members as is shown on factsheet 6. Your patient, Nigel has three children and a grandson. Draw the symbol for Nigel, then his wife, Margaret. Traditionally, women are placed to the right of their partners in a pedigree (Fig. 3). Margaret Nigel DOB 12/10/70 Fig. 3 Next, add Nigel and Margaret’s three children, Harry, Mary, and Elizabeth. Draw a straight line down from the centre of the relationship line between Nigel and Margaret. Then add what looks like a comb, with three teeth pointing down and the symbol for each child attached (Fig. 4). Margaret Nigel DOB 12/10/70 Harry Mary Elizabeth Fig. 4 Nigel and his middle daughter, Mary, both have achondroplasia (a form of restricted growth). To indicate the condition, shade in their symbols and include a key. Mary has a son, Sam, who also has achondroplasia, so you add him and his father, James, to the pedigree (Fig. 5). This three generation pedigree shows that the condition is being passed down the generations. The pattern is consistent with an autosomal dominant mode of inheritance. Margaret Nigel DOB 12/10/70 Harry James Elizabeth Mary achondroplasia Sam Fig. 5 It is important that the person recording the family history ensures that it reflects accurately the information given by the patient. One must recognise that the accuracy of the diagnoses given will depend on how much knowledge is shared within the family, and accuracy of an individual’s recall. The purpose of this toolkit is to assist in the accurate recording of family history details. The accuracy or completeness of the information is something to be considered when the pedigree needs to be interpreted for clinical management, and is the subject of a separate set of factsheets. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series: Part 5 National Genetics Education and Development Centre What and how much information should be included in a pedigree? How can one decide how much information needs to be gathered, and from whom? Pathophysiology Of Genetics And Genetic Testing Discussion

The key is to identify the purpose for taking the family history. Sometimes we may want to ask questions targeted to identify specific family members rather than take a family history about all medical conditions. This could be to: • identify people at a higher probability of being a carrier or of having a genetic condition already known in the family • offer carrier testing to other family members as a result of the antenatal or neonatal screening programmes. At other times, we may want to ask more general questions about medical conditions to build up a detailed picture of the family history to identify: • whether there are any genetic disorders in a family • the number of people with disorders such as diabetes, cardiovascular disease or cancer to use the family history as one of the risk factors when offering advice to an individual about prevention • those families with common disorders (e.g. breast or colorectal cancer) where a single gene disorder may be predisposing to the condition. This is so that individuals can be offered targeted surveillance. How many generations should we include? If in doubt, aim for the usual practice of three generations, particularly to build up a full picture of illness in a family, or to try to deduce a mode of inheritance from the pattern of affected family members. Asking about only two generations or more than four may be appropriate depending on the genetic basis of the condition and family size. How many people should we include? The minimum should be to gather information on first degree relatives (children, siblings and parents) of an individual. This may be sufficient to inform a clinical decision, but equally you may need to supplement this with information about other relatives. This may often be necessary to inform a view about reassurance or referral to a specialist. Key information helpful for drawing a genetic family history (pedigree) A very brief overview of the types of information often required now follows. Specific questions to elicit this information, and how it can be shown on the pedigree are the subjects of factsheet 6. For each key person, record under the pedigree symbol the following information as appropriate: • Name • Date of birth (DOBs are preferable to current ages or estimates) • Relevant symptoms and/or diagnoses and age at diagnosis (if known) • Cause of death and age at death (if known) This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk The previous factsheet showed how pedigree symbols can be connected together to show family relationships. Here are two examples (Fig. 1 & Fig. 2) to show how medical information can be presented in a pedigree. Note that no pedigree is complete without the name of the person who took it, the date it was drawn, and an explanation of any abbreviations. Pedigree taken: 05/05/08 Drawn by H. M. Smith diagnosis death breast cancer cancer d. BC ca Sue 10/10/61 @ 30 BC d. @ 43 metastatic BC Robert 11/11/59 @ 48 prostate ca Fig. 1 This pedigree (Fig. 1) immediately highlights relevant medical information for Robert and his late sister, Sue. It should trigger questions about the occurrence of cancer in other family members. Depending on the medical condition in the family, it might also be appropriate to ask about: • Pregnancy and birth history • Developmental delay and learning disabilities • Dysmorphic features/congenital anomalies • Occupational/environmental exposures • Operations and hospitalisations • Medications. Date pedigree taken: 05/05/08 Drawn by: H. M. Smith DD developmental delay pregnancy loss Angela 02/02/65 12 weeks David 05/05/95 14 weeks Jane 12/12/92 DD Fig. 2 This pedigree (Fig. 2) should trigger questions focussing on developmental delay in any nieces or nephews, recurrent pregnancy losses in other members of the family, or if any diagnostic and/or genetic tests have been performed. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series: Part 6 National Genetics Education and Development Centre Gathering information and drawing a genetic family tree How can busy health professionals gather family history information in an efficient way? This factsheet outlines a set of questions, found useful in clinical practice, which if asked systematically will help to ensure that important information is recorded. A family tree will be built up on the following pages by using the questions. Most people are happy to collect together the required information (often consulting other family members) if they are informed before attending a clinic. When asking for family information, please remember that some people may feel guilty or ashamed that they could have “passed on” an altered gene for a serious condition to another family member. Also, as people may have had recent bereavements, please enquire as sensitively as possible. General questions to gain a quick overview of a genetic family history Each specialty will have key questions about symptoms and signs which would alert the clinician to the possibility that a genetic condition might be present in a family, but the following are helpful in quickly gaining an overview. “Do you have any concerns about diseases or conditions that seem to run on either your or your partner’s side of the family?” “Does anyone have a major medical, physical or mental problem? Has anyone ever needed treatment in hospital? Has anyone ever had any serious illnesses or operations? How old were they at diagnosis?” (Avoid just asking “Is everyone well?” as past medical history may not be offered!) “Have any adults, children or babies died? How old were they and what was the cause of death? Have there been any miscarriages or babies who were stillborn?” The minimum information required for a targeted family history • • Draw the siblings, children and parents (first degree relatives) of your informant, and their names, dates/year of birth and any significant illnesses. It may not be necessary to record names of members of the extended family although it may be important to show how many unaffected people there are in the family. Drawing a family tree Karen Hill has been diagnosed at the age of 35 as having breast cancer. As there are other cases of cancer in her family history, she is concerned about the chances of her children developing cancer. The first step is to build up a family tree to appreciate the relationships of the people with cancer, which will now be illustrated, step by step. The parts of the pedigree newly drawn as a result of the next set of questions will be shown in red. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk 1. Start with the person giving the information (informant) Use a pen (not a pencil) as you are writing a medical record. A pedigree drawing template (such as that devised by the NHS National Genetics Education and Development Centre) can be helpful to achieve uniform symbols. Start at the bottom or top of the page according to whether you will be developing the tree “upwards” from a child, adding parents, aunts, uncles and grandparents, or “downwards” if the informant is a grandparent. The plan should be to move systematically through the family relationships, usually recording partner, children, brothers, sisters and parents moving across and then up/down the generations. “Please may I ask if either of you come from large families with many brothers and sisters or aunts and uncles?” If so, consider rotating the page and drawing in landscape format. Draw the symbol appropriate for the gender of your informant Karen Hill has been diagnosed as having breast cancer at the age of 35 years (Fig. 1). • Mark your informant with an arrow. • Write in her or his name and date of birth and medical information . • Consider asking about occupations and environmental exposures if appropriate to the condition. Karen 30.1.1973 Diag breast cancer age 35 yr Fig. 1 Now ask about partner Karen is married to Andrew (Fig. 2). “Are you married; or do you have a partner?” “Have you been married before or had any previous partners?” Be sensitive when trying to determine if partners are related by blood (a consanguineous relationship). Karen 30.1.1973 Andrew Hill 21.7.72 Diag breast cancer age 35 yr Questions may include: “Are you and your partner related (except by marriage)?” “Are there any surnames or maiden names in common in the family?” “Did any couples in the family have the same surname before they were married to each other?” Fig. 2 2. Ask about the children of the person giving the family history Karen and Andrew have a son and two daughters (Fig. 3). “How many children have you had? Have you lost any children?”

“Are all your children with the same partner or were any with previous partners?” “Please give me the names of your children, and their dates of birth in order of their ages, starting with the eldest first.” If possible draw the firstborn on the left. If there is a current pregnancy, record the date of the last period (LMP) or expected date of delivery (EDD). For some conditions, it may be appropriate to ask about miscarriages, stillbirths or deaths in each partnership. Some people may find this upsetting. Being open often helps: Andrew Hill Karen 30.1.1973 Diag breast cancer age 35 yr 21.7.72 “Have you lost any children?” “Did you lose any babies or have any other pregnancies?” Record the number of weeks for pregnancy losses (“I am sorry to hear of your loss” if it occurred recently). If a pregnancy was terminated (rather than lost spontaneously), sensitively ask if there was a medical reason. Daniel 3.2.1994 Emily 30.4.1997 Sophie 9.10.1999 Fig. 3 3. Next ask about the siblings of the informant, their spouses and their children Karen has a brother Paul, whose daughter Jessica is fit and well. Karen’s mother had a son (John) with a previous partner. John has a daughter (Fig. 4). “How many brothers and sisters do you have; have any of your brothers or sisters died?” “Do they all share the same mother and father?” You may need to draw in their parents at this stage to make the relationships clear. “How many children have each of your brothers/sisters had?” “Did they lose any children during pregnancy or in childhood?” Ask about medical conditions. Karen 30.1.1973 Diag breast cancer age 35 yr Paul Lee 30.11.1975 Susan Jessica 13 yr John Marshall Chloe Fig. 4 This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk 4. Record details about one parent of your informant Karen’s mother Margaret Lee died at 62 yr with breast cancer; Karen wants to know if her daughters are at increased risk. Ernest, Margaret’s first partner, died from lung cancer (Fig. 5). No other cases of breast cancer known in family Ask for name, date/year of birth and any medical conditions. Brian Lee 17.3.1943 Alive and well Do you need to collect details on the parent’s brothers and sisters and their own parents? Deciding how many generations to include usually depends on the reason for taking the pedigree. Margaret 17.4.1946 Died age 62 yr Breast cancer Karen 30.1.1973 Diag breast cancer age 35 yr Ernest Marshall Died age 50 yr lung cancer Heavy smoker Jean ? 70 yr Mary ? 67 yr John Marshall Paul Lee 30.11.1975 Fig. 5 5. Then ask about the other parent Karen’s father had three siblings, but Karen has no further details (Fig. 6). Her side of the family is now complete. No other cases of breast cancer known in family 3 Brian Lee 17.3.1943 Alive and well Karen 30.1.1973 Diag breast cancer age 35 yr Margaret 17.4.1946 Died age 62 yr Breast cancer Ernest Marshall Died age 50 yr lung cancer Heavy smoker Jean ? 70 yr Mary ? 67 yr John Marshall Paul Lee 30.11.1975 Fig. 6 6. Collect information about your informant’s partner and his/her family Return to Karen’s partner, Andrew Hill, and collect information on his side of the family, working systematically through the generations using the same questions as before. Andrew has a brother with haemophilia; their father has diabetes but their mother Patricia aged 52 is well. Her father died at the age of 24 years. He had had problems with excessive bleeding (Fig. 7). To conclude For some genetic conditions it is important to ask: “Originally, where did each of your grandparents come from?” This may help the laboratory target testing to specific gene alterations more common in certain populations. As well as thanking the informant for the information, ask: “Is there anything else you think I should know that I haven’t asked about?” Edith Died age 25 yr Road traffic accident Thomas Price Died age 24 yr “Problem with excessive bleeding” David Hill 54 yr Maturity onset diabetes diag age 52 yr Mark 8.8.1974 Haemophilia Patricia 52 yr Andrew Hill 21.7.72 Karen 30.1.1973 Diag breast cancer age 35 yr Daniel Sophie Emily Most important last steps 3.2.1994 9.10.1999 30.4.1997 • Date and write your name legibly on the pedigree together with an Fig. 7 explanation of any abbreviations. • Record the person giving the information (if you have not already placed an arrow next to their symbol). • Always ensure that you have asked for permission to share family history information with colleagues and/or other family members and note this. The completed family tree is shown on the next page, together with further tips about presenting information. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Daniel 3.2.1994 Emily 30.4.1997 Andrew Hill 21.7.72 This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Names of extended family members may not be necessary unless they are at risk of a genetic condition, or they have a common disease which is clustering in the family. If several conditions run in the family, use different shadings and provide a key. Mark 8.8.1974 Haemophilia Patricia 52 y 3 Sophie 9.10.1999 Karen 30.1.1973 Diag breast cancer age 35 y Edith Died age 25 y Road traffic accident Paul Lee 30.11.1975 Jessica 13 y Susan Margaret 17.4.1946 Died age 62 y Breast cancer Fill in the symbol for people known or reported to be affected; write in other diagnoses underneath the person’s symbol. Brian Lee 17.3.1943 Alive and well Chloe “?” if the informant is not completely sure. Mary ? 67 y Supporting Genetics Education for Health www.geneticseducation.nhs.uk Pedigree taken 5 August 2008 by Nurse C. Martin Date and write your name legibly on the pedigree. Drawing a partner of a sibling may not be necessary unless their child has a significant condition. Draw a sloping line if the person has died; if appropriate, record age and cause of death. Jean ? 70 y No other cases of breast cancer known in family. Include affected and unaffected individuals on both sides of family as this can help in determining if the condition is likely to be genetic (for instance, breast or colorectal cancer). Ernest Marshall Died age 50 y Lung cancer Heavy smoker John Marshall Record at least basic details on both sides of family to avoid missing conditions on the other side of the family and not to appear to apportion blame. Use standardised symbols (circles for females, squares for males). Place a number in a symbol to show unaffected siblings. Consider if it is necessary to record sensitive information that is unlikely to answer a genetic question (such as terminations of pregnancy or issues of paternity not relating to potentially at risk individuals).

ORDER HERE

Thomas Price Died age 24 y “Problem with excessive bleeding” David Hill 54 y Maturity onset diabetes diag age 52 y Put quotation marks around information recorded verbatim. Place male partners on the left if possible. Taking and Drawing a Family History Series: Part 7 National Genetics Education and Development Centre Pedigree drawing exercises The patient narratives below will give you an opportunity to practise drawing pedigrees. The finished pedigrees are overleaf. Family 1 Your patient, Anna, is 35 years old. She has a brother, Brad, who is 32. Anna and Brad are the only children of Charles, who died at 61 from cancer, and Nancy, who is alive and well at 57 years old. Anna is married to Don, who is 36, and they have identical 6-year-old twin boys, James and John. Brad and Linda have a 5-year-old daughter, Sarah, and a 2-year-old son, Michael. Brad and Linda are recently divorced. Family 2 Lily is 28 years old (9.1.80). She has an appointment to look at a wound on her left foot that isn’t healing well. Lily has a younger brother, Nick (23.11.82), and a little sister, Sharon (30.6.84). Lily’s parents are George (10.2.55), who is obese, and Maureen (4.3.58). George’s brother, Edward (18.11.58) is obese. George’s sister, Rachel (21.7.52), has type 2 diabetes. George’s parents are both deceased, and his father died of a heart attack. On her mother’s side, she has three aunts who are all alive and well. Lily’s maternal grandparents are Ralph and Beatrice, who both turned 75 in 2007 (so were born in 1932). Family 3 Try drawing your own or someone else’s genetic family history. Do you need to collect any additional information from other members of the family? This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Pedigree 1 Drawn by: Date: For Pedigrees 1 and 2 • Did you remember to include your name and today’s date on your pedigrees? • Did you mark the person providing the pedigree information (your patient) with an arrow? • Did you include individual names and dates of birth (or in this case current ages)? • Did you connect siblings with a ‘comb’ pointing down? Nancy 57 Charles Cancer @ 55 d. 61 Don 36 Anna 35 Brad 32 James 6 John 6 Michael 2 Linda 28 Sarah 5 Fig. 1 Pedigree 2 Drawn by: Date: • In pedigree 1, did you connect the two individual lines for James and John to signify that they are identical twins. • In pedigree 2, you may or may not have shaded in some of the symbols. • What is important is that the relevant medical information is listed for each individual. • In pedigree 2, if you shaded symbols or used abbreviations, did you include a key? Ralph 1932 d. heart attack Beatrice 1932 3 Rachel 21/7/1952 type 2 diabetes Edward 18/11/1958 obese George 10/2/1955 Lily 9/1/1980 open wound on L foot Maureen 4/3/1958 Nick 23/11/1982 Sharon 30/6/1984 Fig. 2 This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series: Part 8 National Genetics Education and Development Centre Safeguarding the information in a genetic family history A pedigree includes information about the biological relationships within a family, the medical diagnoses and genetic status of family members. This information is usually obtained from one member who gives it in good faith, using details obtained directly from other family members. Information about medical diagnoses in the family may well be known to many people, including friends and acquaintances. However, genetic family information should be held in confidence, but as it may be used to advise other family members it is good practice to gain consent from the person who gave the pedigree for information sharing and make a note of this. The status of information from family pedigrees and its disclosure Most individuals expressly state that they wish pedigree information and genetic test results to be available to other family members and professionals to assist in diagnosis and medical care. Recording information about other people in a family amily (and passing it to health profess professionals) is permissable under the Data Protection Act (under Schedule 3) without ut the explicit consent of all those shown o on the pedigree if the processing is necessary for medical purposes (including the he purposes of preventative medicine, med medical diagnosis, medical research, the provision of care and treatment and the management of healthcare services). This w was the advice that The Joint Committee on Medical Genetics received from om the Information Commissioner. The hea health professional should ask for and record consent that the pedigree may be shared ared with other members of the family if aappropriate, and with other health professionals if necessary for the care of family mily members. If asked to release informat information, it is good practice to review the pedigree to try to ensure that only information mation relevant to the clinical purpose is rreleased; for instance, it may not be necessary to give names on parts of the pedigree. gree. Publishing genetic family histories as part of clinical and research studies Of course, consent from the person giving the pedigree needs to have been obtain obtained. There are some other considerations to be taken into account, because the pedigree can give a great deal of informatio information about biological relationships and health status. If it is imperative that a pedigree gree needs to be published, it is recommen recommended that the minimum amount of information which needs to be disclosed is given on the pedigree figure. For instance, unles unless needing to demonstrate the precise pattern of males and females (affected ed and unaffected) and ages of o onset in the family, is it necessary to signify the sexes and ages of family members? For relatively atively rare conditions, it may be possible for families to identify their family and also deduce not only their status but also that of other family members. Reference Consent and confidentiality in genetic ic practice: guidance on genetic testing and sh sharing genetic information (2005). Report of the Joint Committee on Medical Genetics. London: RCP, RCPath, BSHG. Confidentiality and consent are paramount • • Store the genetic family history information safely to preserve confidentiality. As it may be helpful in advising other family members, gain consent from the person giving the genetic family history, for information to be shared with family members and health professionals. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series National Genetics Education and Development Centre Test your knowledge: a family history puzzle 1 3 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Across Down 1. A pictorial representation of a genetic family history (8) 2. Taking a family history may result in the earlier ____ of a condition (9) 5. If a condition is inherited, it must be caused by an alteration to the ___ 3. The sex of the person in 7 across is ___ (7) material (7) 4. The assessment of this can be informed by details from a genetic family 7. This symbol represents a ___ (9) P history (4) 8. Taking a family history can help to build up ___ with a patient (7) 6. This man and woman are ___ (8) 10. The individuals joined by the double line are related as ___ ___ (5, 7) 9. This symbol indicates a ___ (11) 14. These individuals are ___ (8) 11. The shaded symbol represents the patient’s maternal ___ (4) 17. These twins are ___ (9) 12. Also called ‘changes’ or ‘alterations’; these can be beneficial, harmful or 19. The standard number of generations to include in a family history (5) neutral (9) 20. This couple is ___ (8) 13. This person is ___ (8) 21. The molecule of life (3) 15. This individual is ___ (8) 16. Identifying which people are affected with a condition in a family helps to recognise a ___ of inheritance (7) 18. Used to indicate the patient/person providing information for a pedigree (5) And for a bonus point: Use the letters in the coloured squares to complete the following sentence: Pedigree symbols have been agreed internationally and ___ (12), so that any health professional can look at a patient’s family history and quickly appreciate key information. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre Supporting Genetics Education for Health www.geneticseducation.nhs.uk Family history puzzle answers Across 1. pedigree 5. genetic 7. pregnancy 8. rapport 10. first cousins 14. siblings 17. identical 19. three 20.divorced 21. DNA Down 2. diagnosis 3. unknown 4. risk 6. partners 9. miscarriage 11. aunt 12. mutations 13. affected 15. deceased 16. pattern 18. arrow Bonus answer: standardised This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre Supporting Genetics Education for Health www.geneticseducation.nhs.uk Taking and Drawing a Family History Series National Genetics Education and Development Centre Cancer scenarios Taking a family history can enable you to discuss with the patient and family the possibility of a genetic basis to their diagnosis. Patients are often concerned at the possible implications for other family members. Scenario 1 John is talking to the practice nurse about his concerns because bowel cancer runs in his family. Following the drawing of a family history it can be seen why he is concerned. No other family history of cancer George d. 1990 Died of Alzheimer’s age 75 James b. 14/7/1937 d. 06/12/1999 Died of bowel cancer age 62 William b. 1917 Mary d. 1994 Died of stroke age 76 Thomas b. 18/6/1940 Anne b. 23/4/1941 Edith d. 1999 Died of old age age 83 Stephen b. 18/11/1942 d. 06/1/2008 Died of bowel cancer age 65 Robert d. 1994 Died of pneumonia age 76 Jennifer b. 22/9/1945 d. 23/10/2001 Died of bowel cancer age 56 This medical pedigree was taken by A. GP Date 05/08/2008 John b. 03/3/1966 Fig. 1 Scenario 1 Three family members have died of bowel cancer. It would be important to identify the site of these cancers to see if they are indeed the same, which would increase the chance that these are due to the same genetic condition. However, the three people are not related to one another as first degree family members e.g. parent or full sibling. And there is no evidence of cancer in the closer relatives, or in other generations, which might suggest an increased genetic risk. This pedigree (Fig. 1) therefore demonstrates the importance of considering three generations within a family history. Using the UK National Guidelines, John’s risk would be considered low and whilst he may be offered advice and monitoring, unless symptomatic it would be unlikely he would be offered any invasive screening techniques. Scenario 2 Jane is attending the oncology clinic as she has found a breast lump. She talks to you about her fears for her two young daughters as there seems to be so much cancer in the family. You suggest drawing a family pedigree; an example of this pedigree can be found on the next page (Fig. 2). This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk Arthur b. 1/2/1927 Elizabeth b. 11/7/1953 James b. 6/3/1951 Olive b. 6/11/1928 Michael b. 1928 Peter b. 7/9/1949 Debbie b. 12/4/1952 d. 3/5/1994 Died of breast cancer aged 42 Jane b. 9/7/1976 John b. 4/7/1950 Anne b. 10/10/1931 d. 6/10/1979 Died of breast cancer aged 47 Susan b. 7/11/1953 d. 5/9/1990 Died of ovarian cancer aged 36 Lynda b. 18/6/1957 This medical pedigree was taken by A. GP Date 1/9/2008 Fig. 2 Scenario 2 On taking a genetic family history it is clear that there is a possible pattern within her family. You discuss that whilst you could give her a probability of there being a genetic predisposition in the family based on published information obtained from studies of many families, it is impossible to say there is a definitive genetic cause without further investigations. If following her biopsy breast cancer is diagnosed, you would want to discuss with Jane the services available for genetic investigations and the way that referrals are made. This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre (08/08) Supporting Genetics Education for Health www.geneticseducation.nhs.uk This sheet may be photocopied for non-commercial education purposes for healthcare staff © 2008 NHS National Genetics Education and Development Centre Supporting Genetics Education for Health www.geneticseducation.nhs.uk www.geneticseducation.nhs.uk Pathophysiology Of Genetics And Genetic Testing Discussion