Chapter 064. The Practice of Genetics in Clinical Medicine (Part 7)

Chia sẻ: Thuoc Thuoc | Ngày: | Loại File: PDF | Số trang:10

Thêm vào BST

Báo xấu

80
lượt xem 7
download

Download Vui lòng tải xuống để xem tài liệu đầy đủ

Therapeutic Interventions Based on Genetic Risk for Disease Specific treatments are now available for an increasing number of genetic disorders, whether identified through population-based screening or directed testing (Table 64-2). Although the strategies for therapeutic interventions are best developed for childhood hereditary metabolic diseases, these principles are making their way into the diagnosis and management of adult-onset disorders. Hereditary hemochromatosis illustrates many of the issues raised by the availability of genetic screening in the adult population. For instance, it is relatively common (approximately 1 in 200 individuals of northern European descent are homozygous), and its complications are potentially preventable...

Chủ đề:

Bình luận(0) Đăng nhập để gửi bình luận!

Lưu

Nội dung Text: Chapter 064. The Practice of Genetics in Clinical Medicine (Part 7)

Chapter 064. The Practice of Genetics in Clinical Medicine (Part 7) Therapeutic Interventions Based on Genetic Risk for Disease Specific treatments are now available for an increasing number of genetic disorders, whether identified through population-based screening or directed testing (Table 64-2). Although the strategies for therapeutic interventions are best developed for childhood hereditary metabolic diseases, these principles are making their way into the diagnosis and management of adult-onset disorders. Hereditary hemochromatosis illustrates many of the issues raised by the availability of genetic screening in the adult population. For instance, it is relatively common (approximately 1 in 200 individuals of northern European descent are homozygous), and its complications are potentially preventable through phlebotomy (Chap. 351). The identification of the HFE gene, mutations of which are associated with this syndrome, has sparked interest in the use of DNA-
based testing for presymptomatic diagnosis of the disorder. However, up to one- third of individuals who are homozygous for the HFE mutation do not have evidence of iron overload. Consequently, in the absence of a positive family history, current recommendations include phenotypic screening for evidence of iron overload followed by genetic testing. Whether genetic screening for hemochromatosis will someday be coupled to assessment of phenotypic expression awaits further studies. In contrast to the issue of population screening, it is important to test and counsel other family members when the diagnosis of hemochromatosis has been made in a proband. Testing allows the physician to exclude family members who are not at risk. It also permits presymptomatic detection of iron overload and the institution of treatment (phlebotomy) before the development of organ damage. Table 64-2 Examples of Genetic Testing and Possible Interventions Genetic Disorder Inherita Genes Interventions nce Oncologic Hereditary AD MSH2, Early endoscopic nonpolyposis colon MLH1, MSH6,
cancer PMS1, PMS2, screening TGFBR2 Familial AD APC Early endoscopic adenomatous polyposis screening Nonsteroidal anti-inflammatory drugs Colectomy Familial breast and AD BRCA1 Estrogen ovarian cancer , BRCA2 receptor antagonists Early screening by exams and mammography Consideration of prophylactic surgery Familial AD CDKN Avoidance of
melanoma 2A UV light Screening and biopsies Basal cell nevus AD PTCH Avoidance of syndrome UV light Screening and biopsies Hematologic Factor V Leiden AD F5 Avoidance of thrombogenic risk factors and oral contraceptives Hemophilia A XL F8C Factor VIII replacement Hemophilia B XL F9 Factor IX
replacement Possible gene therapy Glucose 6-PO4 XL G6PD Avoidance of dehydrogenase deficiency oxidant drugs Cardiovascular Hypertrophic AD MYH7, Echocardiograph cardiomyopathy MYBPC3, ic screening TMSA, Early TNNT2, pharmacologic TPM1 intervention Myomectomy Long QT AD KCNQ Electrocardiogra syndrome 1, SCN5A, phic screening HERG, Early MiRP1,
KCNE1, pharmacologic KCNE2 intervention Implantable cardioverter defibrillator devices Marfan syndrome AD FBN1 Echocardiograph ic screening Prophylactic beta blockers Gastrointestinal Familial AR MEFV Colchicine Mediterranean fever treatment Hemochromatosis AR HFE Phlebotomy Pulmonary
α1 Antitrypsin AR PI Avoidance of deficiency smoking Avoidance of occupational and environmental toxins Primary AD BMPR2 Treatment with pulmonary hypertension pulmonary vasodilators Renal Polycystic kidney AD PKHD Prevention of disease 1, PKHD2 hypertension Prevention of urinary tract infections Kidney transplantation Nephrogenic XL, AR AVPR2, Fluid
diabetes insipidus AQP2 replacement Thiazides, amiloride Endocrine Neurohypophyseal AD AVP Replace diabetes insipidus vasopressin Maturity-onset AD Multipl Screen and treat diabetes of the young e genes for diabetes Familial AD CASR Avoidance of hypocalciuric parathyroidectomy hypercalcemia Kallmann XL KAL Induction of syndrome puberty with hormone replacement
Multiple endocrine AD RET Prophylactic neoplasia type 2 thyroidectomy Screening for pheochromocytoma and hyperparathyroidism 21-hydroxylase AR CYP21 Glucocorticoid deficiency and mineralocorticoid treatment Neurologic Malignant AD RYR1 Avoidance of hyperthermia precipitating anesthetics Hyperkalemic AD SCN4A Acetazolamide periodic paralysis Adrenoleukodystr XL ABCD1 Possible bone ophy marrow transplant for
severe childhood CNS form Duchenne and XL DMD Corticosteroids Becker muscular Possible future dystrophy myoblast transfer Familial Parkinson AD SNCA, Amantadine, disease PARK2 anticholinergics, levodopa, monoamine oxidase B inhibitors Wilson disease AR ATP7B Zinc, trientene Abbreviations: AD, autosomal dominant; AR, autosomal recessive; CNS, central nervous system; XL, X-linked