Down Syndrome and Prenatal Diagnosis

Technique of Amniocentesis and CVS

• Amniocentesis: a prenatal diagnosis technique used to detect chromosomal and metabolic abnormalities, and DNA analysis
• CVS (Chorionic Villus Sampling): a prenatal diagnosis technique used to detect chromosomal abnormalities, similar to amniocentesis

Ultrasound Diagnosis

• Used to detect structural defects in many organs, including:
  • CNS (Central Nervous System)
  • Heart
  • Kidney
  • Limbs
• Can detect polydactyly (extra fingers/toes), micrognathia (small jaw), and umbilical hernia (associated with Trisomy 18 in 50% of cases)

Trisomy 21 (Down Syndrome)

• Caused by an extra copy of chromosome 21 (47, +21)
• Frequency increases with increasing maternal age (94%)
• Clinical features include:
  • Brachycephaly (short head)
  • Up-slanting palpebral fissures (eye openings)
  • Epicanthal folds (skin folds at the inner corner of the eyes)
  • Brushfield spots (small white spots on the iris)
  • Flat nasal bridge
  • Folded or dysplastic ears
  • Open mouth
  • Protruding tongue
  • Short neck
  • Excessive skin at the nape of the neck
  • Transverse palmar crease (single palmar crease)
  • Space between the first and second toes
  • Hyper flexibility of joints

Neonatal Features of Trisomy 21

• Flat facial profile
• Dysplasia of pelvis
• Anomalous ears
• Excessive skin at the nape of the neck
• Slanted palpebral fissures
• Hypotonia (low muscle tone)
• Hyper flexibility of joints

Congenital Anomalies (Birth Defects)

• Definition: structural abnormalities present at birth
• Causes: genetic, environmental, and multifactorial factors
• Types of abnormalities:
  • Malformations: occur during organ formation (e.g. cleft lip and palate)
  • Disruptions: result in morphological changes due to exposure to destructive processes (e.g. vascular accidents)
  • Deformations: caused by mechanical forces affecting the fetus (e.g. talipes equinovarus)
  • Syndromes: groups of anomalies occurring together due to a common cause (e.g. Down Syndrome)

Trisomy

• Definition: a condition where certain pairs of chromosomes get an extra chromosome in every cell
• Most common types of trisomy:
  • Trisomy 13 (Patau syndrome)
  • Trisomy 18 (Edwards syndrome)
  • Trisomy 21 (Down syndrome)

Trisomy 18 (Edwards Syndrome)

• Caused by an extra copy of chromosome 18
• Clinical features include:
  • Mental deficiency
  • Growth retardation
  • Prominent occiput
  • Short sternum
  • Ventricular septal defect
  • Micrognathia
  • Low-set malformed ears
  • Flexed digits
  • Hypoplastic nails
  • Rocker-bottom feet

Other Chromosomal Anomalies

• Turner syndrome (45,X): a female missing one X chromosome
• Klinefelter syndrome (47,XXY): a male with an extra X chromosome
• Structural chromosomal anomalies: include chromosomal deletion, duplication, translocation, inversion, and ring and iso chromosomes

Teratogens

• Definition: environmental agents that cause damage to the fetus during the prenatal period
• Examples: viruses, drugs, chemicals, and radiation
• Effect: variation in the development of the embryo, fetus, or child
• Mechanism: the physiological or biological processes that explain the cause or how specific events occur

Environmental Factors

• Infectious agents:
  • Viruses (e.g. rubella, cytomegalovirus, herpes simplex, varicella)
  • Toxoplasmosis
  • Syphilis
• Radiation:
  • Ionizing radiation can kill rapidly proliferating cells, producing any type of birth defect
• Chemical agents:
  • Thalidomide (produces limb defects and heart malformations)
  • Diphenylhydantoin (produces facial defects and mental retardation)
  • Tetracycline (produces bone and teeth anomalies)
  • Aspirin (may cause harm in large doses)
  • Cocaine (may cause birth defects due to its effect as a vasoconstrictor)
  • Alcohol (causes fetal alcohol syndrome)
• Hormones:
  • Androgenic agents (cause masculinization of the genitalia of female embryos)
  • Endocrine hormones (e.g. diethylstilbestrol, cause malformation of the uterus, uterine tubes, upper vagina, and vaginal cancer)
  • Insulin (can cause congenital anomalies)
  • Cortisone (in large doses, may cause cleft palate)
• Maternal disease:
  • Diabetes (can cause variety of malformations, including heart and neural tube defects)
• Nutritional deficiency:
  • Vitamin deficiencies (particularly)
• Heavy metals:
  • Organic mercury (can cause birth defects)