106
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.
Disorders Involving Single
or Multiple Genes
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
C
Genetic and
Congenital
Disorders
6
C h a p t e r
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
