General Characteristics and Types of Mutations
Most chromosomal abnormalities are incompatible with life and are eliminated during early embryogenesis. Viable fetuses predominantly exhibit autosomal trisomies, sex chromosome polysomies, and the single viable monosomy variant — monosomy X.
These pathologies are driven by various types of chromosomal rearrangements: deletions (forming partial monosomies), duplications (partial trisomies), inversions, and translocations. The core clinical presentation across all forms consists of multiple congenital anomalies.
Autosomal Trisomies
Down Syndrome (Trisomy 21) Incidence is 1:700–1:800; the risk increases sharply in mothers over 35 years of age.
- Phenotype: Upward slanted palpebral fissures, epicanthic folds, flat nasal bridge, macroglossia, brachycephaly, clinodactyly of the fifth fingers, single transverse palmar crease, and Brushfield spots on the iris. Muscle hypotonia is pronounced.
- Internal Organs: Atrioventricular septal defect (VSD and deformation of the anterior mitral valve leaflet), duodenal/esophageal atresia or stenosis, and renal dysplasia. Hypoplasia of the frontal lobes of the brain is characteristic.
- Complications: Secondary immunodeficiency and an increased predisposition to leukemias.
Patau Syndrome (Trisomy 13) Incidence is 1:5,000–1:7,000.
- Manifestations: Marked prenatal hypoplasia, bilateral cleft lip and palate, micrognathia, scalp defects, and polydactyly.
- Malformations: Arhinencephaly, microcephaly, Meckel diverticulum, and ectopic pancreatic tissue in the spleen. A diagnostic marker is the excessively lobulated microcystic kidney. Only 5% of affected children survive past one year.
Edwards Syndrome (Trisomy 18) Incidence is 1:5,000–1:7,000.
- Phenotype: Dolichocephaly, microstomia, flexed fingers in a clenched fist, and rocker-bottom feet (short and prominent great toe).
- Malformations: Aplasia of one of the valve cusps of the pulmonary artery or aorta, malrotation of the intestine, and esophageal atresia.
Sex Chromosome Abnormalities and Triploidy
Turner Syndrome (45, X0) Incidence is 1:5,000 live-born females (half of the cases are true monosomy; the remaining 50% are due to isochromosomes or mosaicism, which presents with milder clinical features).
- Manifestations: Short stature, webbed neck (pterygium colli), and lymphedema of the hands and feet in newborns.
- Organs: Coarctation of the aorta, horseshoe kidney, and gonadal dysgenesis, leading to primary amenorrhea and infertility in older individuals.
Triploidy Syndrome (69, XXY / 69, XXX) Rarely seen in live births, but accounts for over 20% of spontaneous abortions. Manifests with microphthalmia, widely spaced eyes (hypertelorism), and syndactyly. Internal malformations include hydrocephalus, neural tube defects, and cystic renal dysplasia. Placental pathology is specific: placental weight is increased, and chorionic villi undergo cystic transformation.
Microcytogenetic and Gene Syndromes
These pathologies are detected exclusively via molecular cytogenetic methods and are associated with microdeletions, microduplications, or single-gene mutations.
- DiGeorge Syndrome (del 22q11). Aplasia of the thymus and parathyroid glands, leading to hypocalcemic tetany/seizures.
- Miller-Dieker Syndrome (del 17p13). Manifests with lissencephaly (smooth brain lacking normal sulci and gyri) and seizures.
- Beckwith-Wiedemann Syndrome (add 11p15). Characterized by somatic overgrowth (gigantism), macroglossia, visceromegaly, and umbilical hernia / omphalocele.
- Tricho-Rhino-Phalangeal Syndrome Type II (del 8q23-24). Multiple exostoses, craniofacial anomalies, and short stature.
- Single-Gene Pathologies (autosomal dominant and recessive): Noonan syndrome (PTPN11 mutation, pulmonic stenosis), Holt-Oram syndrome (TBX5 mutation, aplasia of the radius and thumb), and Meckel-Gruber syndrome (MKS1 mutation, occipital encephalocele and polycystic kidneys).