Porth's Essentials of Pathophysiology, 4e

ongenital disorders are abnormalities of a body structure, function, or metabolism that are present at birth. They affect about a quarter of a million babies in the United States each year and are the leading cause of infant death. 1,2 Congenital disorders may be caused by defective genes (single-gene or multifactorial inheri- tance), chromosomal aberrations, or environmental factors that are active during embryonic or fetal devel- opment (e.g., maternal exposure to infection or toxic chemicals during pregnancy). Although all congenital disorders are by definition present at birth, genetic dis- orders may make their appearance later in life. The scientific understanding of congenital disorders has advanced significantly over the past three decades, largely as a result of the Human Genome Project. In fact, the molecular basis for many single-gene disorders is now known or will likely be known within the next few years. Such research has led to new and exciting insights not only in genetics, but also in the basic patho- physiology of disease. This chapter provides an overview of genetic and other congenital disorders. It concludes with a brief sur- vey of prenatal screening and diagnostic methods. A genetic disorder can be described as a discrete event that affects gene expression in a group of cells during develop- ment. Most genetic disorders are caused by changes in the deoxyribonucleic acid (DNA) sequence that alter the synthesis of a single-gene product. However, some genetic disorders are caused by chromosomal rearrangements that result in deletion or duplication of a group of closely linked genes, or by an abnormal number of chromosomes resulting frommistakes that occur during meiosis or mito- sis. 1–3 Chromosomal disorders are discussed separately. As explained in Chapter 5, the genes on each person’s two chromosomes are arranged in pairs and in strict order, with each gene occupying a specific location or locus . One member of each pair is derived from the Genetic and Congenital Disorders 6 C h a p t e r Disorders Involving Single or Multiple Genes

Disorders Involving Single or Multiple Genes Single-Gene Disorders Autosomal Dominant Disorders Autosomal Recessive Disorders X-Linked Disorders Single-Gene Disorders with Atypical Patterns of Inheritance Genomic Imprinting Triplet Repeat Mutations: Fragile X Syndrome Mitochondrial Gene Disorders Multifactorial Inheritance Disorders Cleft Lip and Cleft Palate Chromosomal Disorders Structural Chromosomal Abnormalities 22q11.2 Deletion Syndrome Numeric Disorders Involving Autosomes Down Syndrome Numeric Disorders Involving Sex Chromosomes Turner Syndrome Klinefelter Syndrome Disorders Due to Environmental Influences Period of Vulnerability Teratogenic Agents Radiation Environmental Chemicals and Drugs Infectious Agents Nutrient Deficiencies Prenatal Screening and Diagnosis Screening and Diagnostic Methods Ultrasonography Maternal Serum Markers Non-Invasive Prenatal Testing (NIPT) Invasive Testing Cytogenetic and Biochemical Analyses

C

106