TRISOMY 21

What is trisomy 21?

Trisomy is characterized by the presence of 3 chromosomes, instead of the normal 2, of any particular chromosome. Trisomy is the most common form of aneuploidy.

How does it happen?

The most common cause of aneuploidy is nondisjunction, the failure of chromosomes to disjoin normally during meiosis (). Nondisjunction can occur during meiosis I or II or during mitosis, although maternal meiosis I is the most common nondisjunction in aneuploidies (e.g., Down syndrome, trisomy 18). After meiotic nondisjunction, the resulting gamete either lacks a chromosome or has 2 copies instead of 1 normal copy, resulting in a monosomic or trisomic zygote, respectively.

How to diagnose trisomy 21 at birth?

How to suspect antenatally?

What are the key clinical features?

General.

Hypotonia with tendency to keep mouth open and protrude the tongue, diastasis recti, hyperflexibility of joints, relatively small stature with awkward gait, increased weight in adolescence.

Central Nervous System.

Intellectual disability.

Craniofacial.

Brachycephaly; mild microcephaly with upslanting palpebral fissures; thin cranium with late closure of fontanels; hypoplasia to aplasia of frontal sinuses, short hard palate; small nose with low nasal bridge and tendency to have inner epicanthal folds.

Eyes.

Speckling of iris (Brushfield spots) with peripheral hypoplasia of iris; fine lens opacities by slit lamp examination (59%); refractive error, mostly myopia (70%); nystagmus (35%); strabismus (45%); blocked tear duct (20%); acquired cataracts in adults (30% to 60%).

Ears.

Small; overfolding of angulated upper helix; sometimes prominent; small or absent earlobes; hearing loss (66%) of conductive, mixed, or sensorineural type; fluid accumulation in middle ear (60% to 80%).

Dentition. Hypoplasia, irregular placement, fewer caries than usual, periodontal disease.

Neck.

Short with loose folds of skin. Hands. Relatively short metacarpals and phalanges; hypoplasia of midphalanx of fifth finger (60%) with clinodactyly (50%), a single crease (40%), or both; simian crease (45%); distal position of palmar axial triradius (84%); ulnar loop dermal ridge pattern on all digits (35%).

Feet.

Wide gap between first and second toes, plantar crease between first and second toes, open field dermal ridge patterning in hallucal area of sole (50%).

Pelvis.

Hypoplasia with outward lateral flare of iliac wings and shallow acetabular angle.

Cardiac.

Anomaly in approximately 40%; endocardial cushion defect, ventricular septal defect, patent ductus arteriosus, auricular septal defect, and aberrant subclavian artery, in decreasing order of frequency; mitral valve prolapse with or without tricuspid valve prolapse and aortic regurgitation by 20 years of age; risk for regurgitation after 18 years of age.

Skin.

Cutis marmorata, especially in extremities (43%); dry, hyperkeratotic skin with time (75%); infections in the perigenital area, buttocks, and thighs that begin as follicular pustules in 50% to 60% of adolescents.

Hair.

Fine, soft, and often sparse; straight pubic hair at adolescence.

What are the medical problems in down syndrome?

Hearing problems

Vision problems

cataracts

Refractive errors

Obstructive sleep apnea

Otitis media

Congenital heart disease

Hypodontia and delayed dental eruption

Gastrointestinal atresias

Thyroid disease Seizures

Hematologic problems

Anemia Iron deficiency

Transient myeloproliferative disorder

Leukemia

Celiac disease

Atlantoaxial instability

Autism

Hirschsprung disease

How do you manage them?

Affected individuals are more prone to congenital heart defects (50%) such as atrioventricular septal defects, ventricular septal defects, isolated secundum atrial septal defects, patent ductus arteriosus, and tetralogy of Fallot.

Pulmonary complications include recurrent respiratory infections, sleep-disordered breathing, laryngo- and tracheobronchochomalacia, tracheal bronchus, pulmonary hypertension, and asthma.

Congenital and acquired gastrointestinal anomalies (celiac disease) and hypothyroidism are common ).

Other abnormalities include megakaryoblastic leukemia, immune dysfunction, diabetes mellitus, seizures, alopecia, juvenile idiopathic arthritis, and problems with hearing and vision.

Alzheimer disease–like dementia is a known complication that occurs as early as the 4th decade and has an incidence 2-3 times higher than sporadic Alzheimer disease. Most males with Down syndrome are sterile, but some females have been able to reproduce, with a 50% chance of having trisomy 21 pregnancies. Two genes (DYRK1A, DSCR1) in the putative critical region of chromosome 21 may be targets for therapy.

Developmental delay is universal (Tables 98.6 and 98.7 and Fig. 98.10). Cognitive impairment does not uniformly affect all areas of development. Social development is often relatively spared, but autism spectrum disorder can occur. Children with Down syndrome have considerable difficulty using expressive language

Compared with the general population, children with Down syndrome are at increased risk for behavior problems; psychiatric comorbidity is an estimated 18–38% in this population. Common behavioral difficulties that occur in children with Down syndrome include inattentiveness, stubbornness, and a need for routine and sameness. Aggression and self-injurious behavior are less common in this population than other children with similar degrees of intellectual disability from other etiolo-gies. All these behaviors can respond to educational, behavioral, or pharmacologic interventions.

How do we follow up?

How we can prevent it?

Chromosome analysis is indicated in every person suspected of having Down syndrome. If a translocation is identified, parental chromosome studies must be performed to determine whether one of the parents is a translocation carrier, which carries a high recurrence risk for having another affected child. That parent might also have other family members at risk.

Translocation (21;21) carriers have a 100% recurrence risk for a chromosomally abnormal child, and other robertsonian translocations, such as t(14;21), have a 5–7% recurrence risk when transmitted by females. Genomic dosage imbalance contributes through direct and indirect pathways to the Down syndrome phenotype and its phenotypic variation.