Genetics for Nurses in Adult Disciplines A guide to recognition and referral of congenital and genetic disorders AUTHORS: Golder N. Wilson MD PhD, 1 Vijay Tonk PhD, 2 REVIEWERS: Shirley Karr BSN RN, 3 Joanna K. Spahis BSN CNS, 4 Shirley Myers, 5 RNC, MSN, FNP, and Sherry Letalian RN 6
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A guide to recognition and referral of congenital and genetic disorders
Golder N. Wilson MD PhD,1 Vijay Tonk PhD,2
Shirley Karr BSN RN,3 Joanna K. Spahis BSN CNS,4 Shirley Myers,5 RNC, MSN, FNP, and Sherry Letalian RN6
1Clinical Professor of Pediatrics, Texas Tech University Health Science Center at Lubbock and Private Practitioner, KinderGenome Genetics, Dallas Texas; 2Professor of Pediatrics and Obstetrics-Gynecology; Director, Cytogenetics Laboratory, Texas Tech University Health Science Center at Lubbock;3Genetics Coordinator, Maternal-Fetal Medicine and Genetics, Texas Tech University Health Sciences Center at Amarillo;4Pediatric Clinical Nurse Specialist in Genetics and Coordinator of the Down Syndrome Clinic, Department of Genetics, Children’s Medical Center of Dallas5Women’s Health Nurse Practitioner, Maternal-Fetal Medicine and Genetics, Texas Tech University Health Sciences Center at Amarillo;6Pediatric Clinic Coordinator, Department of Pediatrics, Texas Tech University Health Sciences Center, Lubbock
This presentation was designed as part of the GEN-ARM (Genetics Education Network for Nursing Assessment, Recognition, and Management) for the Mountain States Region Genetics Collaborative (MSRGCC); contact www.mostgene.org or Ms. Joyce Hooker at [email protected]
Genetic diseases affect 5-10% of children
Nurses can recognize and refer genetic disorders without need for esoteric genetic knowledge
We will now present cases where your nursing skills and alertness (REYDAR=Recognize, EYDentify, Assess, Refer) can greatly benefit children with genetic diseases.
These cases will introduce you to simple principles of genetics that will give you confidence in recognizing these patients and foster a medical home
These cases and principles are geared to the nursing genetics primer and resources on the GENARM CD
Newborn with large head and deformed bones with fractures by x-ray
The family history indicated that the mother and other relatives had mild features of osteogenesis imperfecta or brittle bone disease (see Chapter 2)
Suspicion of genetic disease underlying this unusual infant led to referral and genetic counseling for this autosomal dominant disease—mother’s guilt about her accident was assuaged and she learned she had a 50% chance each of her future children would have OI
Categories of genetic disease relate to the steps from gene to family (genetic hierarchy)
Sickle cell anemia is recessive, requiring both distinctive family patternsβ-globin alleles to be abnormal (SS versus AS trait or AA normal).
Sickle cell anemia can be predicted (25% risk for next child) and tested (abnormal S protein or gene)
Other inherited anemias can be related to different abnormal globin alleles (C, D, E, thassemias).
A or S
Know categories, not rare diseases (genotype Oo)
Mendelian diseases reflect transmission of single genes (abnormal alleles) = DNA diagnosis
Multifactorial diseases reflect multiple abnormal genes plus environment = DNA/HLA markers
Many genes altering development cause isolated birth defects like cleft palate
Many genes altering enzyme pathways cause common metabolic diseases
(e.g., adult-onset diabetes, hyperlipidemia)
Many genes altering organ function(s) produce adult diseases (e.g., schizophrenia)
Chromosomal diseases imbalance multiple genes and cause multiple birth defects = Karyotype
REYDAR of common adult presentations (genotype Oo)
Recognition → Category → Referral ↔ Medical home
(see Chapter 1)
Women with poorly controlled diabetes have a 3-5 fold increased risk for congenital anomalies in their fetus that can be remembered by 3Cs—cranial, cardiac, and caudal anomalies. Cranial defects can include anencephaly as in case 9P or holoprosencephaly (photo at right); caudal defects underdevelopment of the sacrum/lower limbs (caudal regression) or spina bifida. Anomaly patterns like the VATER association (192350) or Goldenhar syndrome (164210) also occur at higher frequency in infants of diabetic mothers.
Case 14P: Man whose father had heart attack at age 41 (hypercholesterolemia)
A nurse practitioner in a family practice clinic performs a routine physical on a man of 35 for insurance purposes. He notes on his preassessment form mention of the man’s father who died of a heart attack at age 41. He completes a more detailed family history indicating that the man has two older brothers and two younger sisters, and that one of the older brothers has had two heart attacks and bypass surgery at age 45. The man’s father was adopted, and his mother is in good health with no heart disease in her family. What concerns should be raised?
Diagram of gene and its encoded LDL receptor protein that imports
cholesterol into cells—the position of mutation (shown below gene) determine the
severity of hypercholesterolemia
Chromosome disorders can be diagnosed by a routine karyotype, performed on cells from individuals (blood) or fetuses (blood by fetoscopy, dividing villus cells from chorionic villus sampling, amniotic fibroblasts from amniotic fluid). This testing requires at least 5-7 days for results.
13 karyotype, performed on cells from individuals (blood) or fetuses (blood by fetoscopy, dividing villus cells from chorionic villus sampling, amniotic fibroblasts from amniotic fluid). This testing requires at least 5-7 days for results.
Cloned DNA segment
from target chromosome
13, X, Y
No culture or need for
Now a rapid FISH test is available that does not require stimulation of cell division and gives results within 2-4 hours. Rapid FISH highlights chromosomes commonly involved in disorders—e.g., 13 (Patau syndrome), 18 (Edwards syndrome), or 21 (Down syndrome), showing three versus the normal two FISH signals in each cell nucleus (X and Y probes also show Turner syndrome ordocument sex in cases of ambiguous genitalia)
See Chapter 7 for more information
Table 4.1. Multifactorial Disorders in the United States
*Ranks first for neonatal causes of death; approximate scale: ++++ (100% of predisposition due
to genetic factors as for Mendelian disorders) to + (20% of predisposition due to genetic factors)
Multifactorial Disorders karyotype, performed on cells from individuals (blood) or fetuses (blood by fetoscopy, dividing villus cells from chorionic villus sampling, amniotic fibroblasts from amniotic fluid). This testing requires at least 5-7 days for results.
Multifactorial disorders: For some (e.g., coronary artery disease), single genes of major effect (e.g., those regulating cholesterol) are good risk markers)
Recognizing at-risk children or adolescent females provides important opportunities for nursing education and prevention (see chapter 4)
Case 15P: Discussion cancer at young ages.
Besides recognition of “advanced” maternal age with discussion of increased risks for chromosome abnormalities, the nurse should address increased susceptibility to breast and ovarian cancer. Although not necessarily pertinent to the current pregnancy, the woman has increased risks for breast cancer and should know about options for breast cancer gene testing. Mutations in the breast cancer genes BRCA1 (OMIM #113705) and BRCA2 (OMIM #600185) account for about 10% of breast cancer, characterized by its early onset and association with ovarian cancer. Testing would ideally be performed on one of the woman’s affected relatives, ascertaining the presence of BRCA mutations versus usually multifactorial breast cancer. If positive, the woman should be informed about her 50% risk to transmit the mutation to each child.
. cancer at young ages.
Case 13P: Couple with maternal history of mental retardation
Bob and June present to a nurse practitioner for prenatal care at an estimated 6 weeks of pregnancy. Bob is 26, June 24, and they had a normal daughter Karen two years ago with no pregnancy or delivery problems. Both are healthy and of Caucasian ancestry, and Bob’s family history is normal The nurse finds that June is an only child, but that her mother Gail has two brothers who have mental retardation. In addition, Gail has a sister Joan with with two boys and a girl, and one boy Eric has mental retardation thought due to birth injury. Gail’s other sister Jill has three boys and two girls, and her eldest son Jim has mental retardation of unknown cause. One of Jill’s daughters has also had learning problems that caused her to drop out of high school, and she has a preschool son Bert with speech delay. What concerns should the nurse address?
Gail cancer at young ages.
Case 13P: Discussion
Besides the usual options for genetic and fetal screening (ultrasound, quad screen, cystic fibrosis screening), the nurse should recognize the positive family history and recommend genetic evaluation. The presence of several relatives with the same condition (mental disability) brings up the possibility of Mendelian disease, and sketching of the family pedigree (below) would suggest an X-linked disorder associated with mental retardation. Genetic evaluation would inform June that her mother Gail has a 50% chance and she a 25% chance to be a carrier for the X-linked disease.
Case 13P: Discussion cancer at young ages.
The X-linked fragile X syndrome (OMIM #300624) is the most common genetic cause of mental disability with an estimated incidence of 1 in 2000 males. Since June is early in her pregnancy, a fragile X DNA test could be performed on one of her male relatives to confirm or exclude this diagnosis. It would be ideal if one of her affected male relatives could be evaluated by a clinical geneticist so that the diagnosis of fragile X syndrome or another of the >20 syndromes associated with X-linked mental disability could be suspected.
11. A woman is diagnosed with Crohn’s disease, and wishes to know the risk that her daughter will develop the disease. She is otherwise normal with an unremarkable family history. The likely inheritance mechanism and her daughter’s risk would be: