Chapter 064. The Practice of Genetics in Clinical Medicine (Part 8) pot

Chapter 064. The Practice of Genetics
in Clinical Medicine
(Part 8)

Preventive measures and therapeutic interventions are not restricted to
metabolic disorders. Identification of familial forms of long QT syndrome,
associated with ventricular arrhythmias, allows early electrocardiographic testing
and the use of prophylactic antiarrhythmic therapy, overdrive pacemakers, or
defibrillators (Chap. 226). Individuals with familial hypertrophic cardiomyopathy
can be screened by ultrasound, treated with beta blockers or other drugs, and
counseled about the importance of avoiding strenuous exercise and dehydration
(Chap. 231). Likewise, individuals with Marfan syndrome can be treated with beta
blockers and monitored for the development of aortic aneurysms (Chap. 242).
Individuals with α
1
antitrypsin deficiency can be strongly counseled to avoid
cigarette smoking and exposure to environmental pulmonary and hepatotoxins.
Various host genes influence the pathogenesis of certain infectious diseases in
humans, including HIV (Chap. 182). The factor V Leiden allele increases risk of
thrombosis (Chap. 59). Approximately 3% of the worldwide population is
heterozygous for this mutation. Moreover, it is found in up to 25% of patients with
recurrent deep-vein thrombosis or pulmonary embolism. Women who are
heterozygous or homozygous for this allele should therefore avoid the use of oral
contraceptives and receive heparin prophylaxis after surgery or trauma.
The field of pharmacogenomics seeks to identify genes that alter drug
metabolism or confer susceptibility to toxic drug reactions. Pharmacogenomics
permits individualized drug therapy, resulting in improved treatment outcomes,
reduced toxicities, and more cost-effective pharmaceutical care. Examples include
succinylcholine sensitivity, thiopurine methyltransferase (TPMT) deficiency,
malignant hyperthermia, dihydropyrimidine dehydrogenase deficiency, the
porphyrias, and glucose-6-phosphase dehydrogenase (G6PD) deficiency.

As noted above, the identification of genes that increase the risk of specific
types of neoplasia is rapidly changing the management of many cancers.
Identifying family members with mutations that predispose to FAP or hereditary
nonpolyposis colon cancer (HNPCC) can lead to recommendations of early cancer
screening or prophylactic surgery (Chap. 87). Similar principles apply to familial
forms of melanoma, basal cell carcinoma, and cancers of the breast, ovary, and
thyroid gland. It should be recognized, however, that most cancers harbor several
distinct genetic abnormalities by the time they acquire invasive or metastatic
potential (Chaps. 79 and 80). Consequently, the major impact of genetic testing in
these cases is to allow more intensive clinical screening, as it remains very
challenging to predict disease penetrance, expression, or clinical course.
Although genetic diagnosis of these and other disorders is only beginning
to be used in the clinical setting, predictive testing holds the promise of allowing
earlier and more targeted interventions that can reduce morbidity and mortality.
We can expect the availability of genetic tests to expand. A critical challenge for
physicians and other health care providers is to keep pace with these advances in
genetic medicine and to implement testing judiciously.
Further Readings
Clayton EW: Ethical, legal, and social implications of genomic medicine. N
Engl J Med 349:562, 2003 [PMID: 12904522]
Collins FS, Watson JD: Genetic discrimination: Time to act. Science
302:745, 2003 [PMID: 14593134]
Ensenauer RE: Genetic testing:
Practical, ethical, and counseling
considerations. Mayo Clin Proc 80:63, 2005 [PMID: 15667031]
Guttmacher AE, Collins FS: Genomic medicine—
a primer. N Engl J Med
347:1512, 2002 [PMID: 12421895]
Harper PS: Practical Genetic Counselling, 5th ed. Oxford,
Butterworth

Heinmann, 1998
McCandless SE et al: The burden of genetic disease on inpatient care in a
children's hospital. Am J Hum Genet 74:121, 2004 [PMID: 14681831]
Wolfberg AJ: Genes on the web—Direct-to-c
onsumer marketing of genetic
testing. N Engl J Med 355:543, 2006 [PMID: 16899772]