Down syndrome, or Trisomy 21, is a genetic syndrome caused by a triplication of chromosome 21. It occurs in about 1/800 to 1/1000 live births. Down syndrome is thus one of the most common genetic syndromes and the number one genetic cause of mental retardation. 95% of the time, Down syndrome is caused by maternal non-disjunction of chromosome 21, 4% of the time; it is due to an unbalanced translocation between chromosome 21 and, usually, chromosome 14. 1% of the time, mosaicism is present, where one normal cell line exists, and one with trisomy 21 is present as well.

Risk Factors
1. Advance maternal age
2. Previous child with Trisomy 21

Symptoms

Physical characteristics that are common in persons with Down syndrome, and that should raise suspicion in the neonate are:

1. Hypotonia
2. Upward slanting palpebral fissures
3. Brachycephaly- flat occiput
   
4. Clinodactly with short 5^th finger
5. Protruding tongue
6. Flat nasal bridge
7. Epicanthal folds
8. Brushfield spots ( spots on iris)
9. Ear abnormalities (low set ears, stenotic meatus)
10. Single palmar crease
11. Congenital cardiac defect (VSD, AV canal defects)
12. Duodenal atresia
13. Low IQ (mean of 50)
14. Loose nuccal skin
15. Short Fingers
    

Diagnosis of Down syndrome can be made in both the pre-natal and post-natal periods. Pre-natal diagnosis of Down syndrome is suspected with an abnormal triple screen test (low AFP, low estriol and high b-HCG). A definitive diagnosis is made with a karyotye of fetal cells, done by chorionic villus sampling between 9 and 11 weeks, or by amniocentesis, between 16 to 18 weeks. Post-natal diagnosis can be made when an infant presents with signs or physical characteristics of Down syndrome. A karyotype analysis will reveal the triplicate material of chromosome 21. It may be advisable to refer parents to a geneticist at this time, to evaluate future risk of recurrence based on maternal age and karyotype.

Complications and Treatment

In the care of children with Down syndrome, it is important to note that there are certain complications and risks that are higher in these patients than in the average population. Therefore, anticipatory guidance is essential. Certain medical complications that occur in-patients with Down syndrome include:

1. Congenital cardiac defects — these can occur in 40 to 60% of patients with Down’s syndrome, and include complete AV canal defects, VSD and tetralogy of Fallot. Because of this risk, ALL newborns with Down syndrome should have an echocardiogram and ECG to screen for heart defects. If found, the patient should be referred to a pediatric cardiologist.
2. Ear, nose and throat defects — Children with Down syndrome may have ear abnormalities that can predispose to serous otitis media, pharyngitis and sinusitis. Infections should be treated aggressively, and hearing should be evaluated at 6 months of age. Because of floppy airways, increase incidence of obstructive sleep apnea.
   
3. Orthopedic issues- Alanto-axial or alanto-occipital instability, scoliosis and foot deformities are common orthopedic problems in children with Down syndrome. This may necessitate referral to a specialist if problems are discovered. The American Academy of Pediatrics recommends that children with Down syndrome should have screening radiographs at 3-5 years of age to look for alantoaxial instability, particularly if they are involved in contact sports.
4. Gastrointestinal defects- newborns with feeding or stooling problems should be suspected of having some type of GI defect. Common GI issues in patients with Down syndrome include: duodenal atresia, esophageal atresia, tracheoesophageal fistula, and imperforate anus. An upper GI series or barium enema may be necessary to rule out a GI malformation. There is also a high rate of Hirschsprung's disease.
5. Developmental deficits- children with Down syndrome have decreased cognitive function, but this varies (low normal intelligence to profoundly retarded) and is impossible to predict at birth. The physician should evaluate development at each visit, and referral should be made as early as possible to early intervention programs, as appropriate therapy can help to minimize developmental delay.
6. Other issues: These are numerous and can include: cataracts, lukemeoid reactions, seizures, dental problems, skin dryness and thyroid disease.

1.   Growth and weight should be plotted to watch for other disorders such as hypothyroidism, celiac disease, or excessive weight gain

2.  Obesity prevention should begin at 24 months of age which includes monitoring diet and physical activity

3. All Down’s infants should be evaluated by a pediatric cardiologist to detect abnormalities

4.  Newborn hearing screens that are not passed merit a full evaluation

5. CBC & differential should be done at birth to screen for leukemias since Down’s infants are at greater risk.

6. Dental visits are encouraged every 6 months due to increased risk of periodontal disease

7. Radiographs at 3-5 years of age to monitor for atlantoaxial instability

References:

1. American Academy of Pediatrics. Health Supervision for Children with Down Syndrome. Pediatrics. Vol 107. No. 2 2001, pp. 855-859.
2. Sanez, R. Primary Care of Infants and Young Children with Down Syndrome. American Family Physician. Vol 59, No. 2, 1999: pp. 329-395.
3. Scioscia, A., Jones, K. Responding to Parental Concerns After a Prenatal Diagnosis of Trisomy 21. Pediatrics. Vol. 107. No. 4, 2001: pp. 204-208.
4. Simpson J. Choosing the Best Prental Screening Protocol.  NEJM Nov 10, 2005