Birth Defects and Prenatal Diagnosis
Introduction to Birth Defects
• Definition:
o Birth Defect, Congenital Malformation, Congenital Anomaly: These are terms used
to describe any abnormality in structure, behavior, function, or metabolism
present at birth. They can be visible structural defects, functional abnormalities, or
even metabolic issues not immediately apparent.
o Teratology: This field studies birth defects and how genetic or environmental
factors contribute to their occurrence.
o Dysmorphology: A subfield of genetics focusing on the pattern recognition of
congenital anomalies and understanding the etiology of these defects.
• Epidemiology of Birth Defects:
o Incidence:
§ Major Structural Anomalies: Occur in 3-5% of all live births and are the
leading cause of infant mortality, accounting for about 25% of neonatal
deaths.
§ Minor Anomalies: Found in approximately 15% of all newborns. Minor
anomalies include small physical abnormalities that do not impair function
but can indicate a higher risk of major defects.
o Classification of Causes:
§ Unknown Etiology: 40-45% of birth defects are idiopathic, with no
identifiable cause.
§ Genetic Causes:
§ Include single-gene mutations, chromosomal abnormalities (e.g.,
trisomy 21 in Down syndrome, monosomy X in Turner syndrome),
and mutations affecting structural or regulatory genes.
§ Environmental Agents: Teratogens such as viruses, chemicals, radiation,
or maternal illnesses.
§ Multifactorial Inheritance: Results from the interaction between multiple
genetic predispositions and environmental factors, such as neural tube
defects (NTDs) involving genetic susceptibility and folate deficiency.
, Types of Birth Defects
Malformations
• Definition and Mechanism:
o Occur during organogenesis (typically between the third and eighth weeks of
gestation), when primary tissue structures are being formed.
o Examples include cleft lip/palate, cardiac septal defects, and polydactyly (extra
digits).
• Timing: This period, known as organogenesis, is the time when the embryo is most
susceptible to malformation.
Disruptions
• Definition: Result from the destruction of an originally normal structure, often due to
extrinsic factors that act after initial organ formation.
• Examples:
o Amniotic Band Syndrome: Results from fibrous amniotic bands wrapping around
limbs or other body parts, leading to constriction, deformations, or even
amputation.
o Vascular Disruptions: These may be caused by ischemic events, such as vascular
accidents that disrupt blood flow, leading to conditions like transverse limb defects.
Deformations
• Definition: Caused by mechanical forces that alter an already formed structure. Often
occur later in gestation, primarily affecting the musculoskeletal system.
• Example:
o Clubfoot (Talipes Equinovarus): Typically caused by uterine constraint, where
decreased amniotic fluid (oligohydramnios) or fetal positioning restricts normal limb
movement, resulting in deformity.
• Reversibility: Many deformations can resolve spontaneously or with conservative therapy
such as physiotherapy or casting after birth.
Dysplasia
• Definition: Refers to abnormal cellular organization within tissues, often due to underlying
genetic mutations.
• Example:
o Skeletal Dysplasia: Conditions like achondroplasia, where abnormal growth and
differentiation of cartilage result in dwarfism and skeletal abnormalities.
Introduction to Birth Defects
• Definition:
o Birth Defect, Congenital Malformation, Congenital Anomaly: These are terms used
to describe any abnormality in structure, behavior, function, or metabolism
present at birth. They can be visible structural defects, functional abnormalities, or
even metabolic issues not immediately apparent.
o Teratology: This field studies birth defects and how genetic or environmental
factors contribute to their occurrence.
o Dysmorphology: A subfield of genetics focusing on the pattern recognition of
congenital anomalies and understanding the etiology of these defects.
• Epidemiology of Birth Defects:
o Incidence:
§ Major Structural Anomalies: Occur in 3-5% of all live births and are the
leading cause of infant mortality, accounting for about 25% of neonatal
deaths.
§ Minor Anomalies: Found in approximately 15% of all newborns. Minor
anomalies include small physical abnormalities that do not impair function
but can indicate a higher risk of major defects.
o Classification of Causes:
§ Unknown Etiology: 40-45% of birth defects are idiopathic, with no
identifiable cause.
§ Genetic Causes:
§ Include single-gene mutations, chromosomal abnormalities (e.g.,
trisomy 21 in Down syndrome, monosomy X in Turner syndrome),
and mutations affecting structural or regulatory genes.
§ Environmental Agents: Teratogens such as viruses, chemicals, radiation,
or maternal illnesses.
§ Multifactorial Inheritance: Results from the interaction between multiple
genetic predispositions and environmental factors, such as neural tube
defects (NTDs) involving genetic susceptibility and folate deficiency.
, Types of Birth Defects
Malformations
• Definition and Mechanism:
o Occur during organogenesis (typically between the third and eighth weeks of
gestation), when primary tissue structures are being formed.
o Examples include cleft lip/palate, cardiac septal defects, and polydactyly (extra
digits).
• Timing: This period, known as organogenesis, is the time when the embryo is most
susceptible to malformation.
Disruptions
• Definition: Result from the destruction of an originally normal structure, often due to
extrinsic factors that act after initial organ formation.
• Examples:
o Amniotic Band Syndrome: Results from fibrous amniotic bands wrapping around
limbs or other body parts, leading to constriction, deformations, or even
amputation.
o Vascular Disruptions: These may be caused by ischemic events, such as vascular
accidents that disrupt blood flow, leading to conditions like transverse limb defects.
Deformations
• Definition: Caused by mechanical forces that alter an already formed structure. Often
occur later in gestation, primarily affecting the musculoskeletal system.
• Example:
o Clubfoot (Talipes Equinovarus): Typically caused by uterine constraint, where
decreased amniotic fluid (oligohydramnios) or fetal positioning restricts normal limb
movement, resulting in deformity.
• Reversibility: Many deformations can resolve spontaneously or with conservative therapy
such as physiotherapy or casting after birth.
Dysplasia
• Definition: Refers to abnormal cellular organization within tissues, often due to underlying
genetic mutations.
• Example:
o Skeletal Dysplasia: Conditions like achondroplasia, where abnormal growth and
differentiation of cartilage result in dwarfism and skeletal abnormalities.
