Down (Trisomy 21) Syndrome
Down (Trisomy 21) Syndrome: Excerpt from The 5-Minute Pediatric Consult
Esther K. Chung, MD, MPH
Down Syndrome - BASICS
Down Syndrome - description
Syndrome 1st described by John Langdon Down in 1866 consisting of multiple abnormalities, including hypotonia, flat facies, upslanting palpebral fissures, and small ears; also called “trisomy chromosome 21.” Other abnormalities include:
- Congenital heart disease (40–50%; most not symptomatic as newborn):
- Atrioventricular (AV) canal (60% of those with congenital heart disease)
- Ventriculoseptal defect (VSD)
- Patent ductus arteriosus (PDA)
- Atrioseptal defect (ASD)
- Aberrant subclavian artery
- Tetralogy of Fallot
- Hearing loss (66–75%): Sensorineural and conductive
- Strabismus (33–45%)
- Nystagmus (15–35%)
- Fine lens opacities (by slit-lamp examination 59%), cataracts (1–15%)
- Refractive errors (50%)
- Nasolacrimal duct stenosis
- Delayed tooth eruption
- Tracheoesophageal fistula
- GI atresia (12%)
- Celiac disease
- Meckel diverticulum
- Hirschsprung disease (<1%)
- Imperforate anus
- Renal malformations
- Hypospadias (5%)
- Cryptorchidism (5–50%)
- Testicular microlithiasis
- Thyroid disease (15%): Congenital hypothyroidism, hyperthyroidism
- Transient myeloproliferative disorder, neonatal (leukemoid reaction)
- Neonatal polycythemia
- Leukemia (<1%; 10–30 times greater risk than in general population)
- Retinoblastoma and testicular germ-cell tumors (slightly greater risk than in general population)
- Infertility, especially in males
- Obesity
- Alopecia areata (10–15%)
- Seizures (5–10%), usually myoclonic
- Alzheimer disease (nearly all over age 40 years)
- Mild to moderate mental retardation (IQ range 25–70)
- Dry, hyperkeratotic skin (75%)
Down Syndrome - epidemiology
- Male > Female (1.3:1)
- Best recognized and most frequent chromosomal syndrome of humans
- 1 of the 3 most common autosomal trisomies in humans (others are trisomy 18 and 13)
- Most common autosomal chromosomal abnormality causing mental retardation
- >50% of trisomy 21 fetuses are spontaneously aborted in early pregnancy.
Down Syndrome - incidence
1/600–1/800 live births, although incidence varies with maternal age:
- 1/1,500 for maternal ages 15–29 years
- 1/800 for maternal ages 30–34 years
- 1/270 for maternal ages 35–39 years
- 1/100 for maternal ages 40–49 years
Down Syndrome - risk factors
Down Syndrome - genetics
- 94–97% of cases are the result of chromosomal nondisjunction (failure to segregate during meiosis) in the maternal DNA.
- <5% of cases are the result of paternal nondisjunction.
- Of live births, 2.4% are mosaic (nondisjunction occurs after conception; 2 cell lines are present); generally less severely affected.
- Remainder of cases are the result of translocations between chromosome 21 and 14 [t(14q21q)]; rarely between 21 and 13 or 15; 50% of translocations are sporadic de novo events; 50% result from balanced translocations in 1 parent.
Down Syndrome - DIAGNOSIS
Down Syndrome - signs & symptoms
Down Syndrome - history
- Check for previous history of infant with Down syndrome in the family.
- Growth and developmental status
- Feeding problems
- Snoring, signs of sleep apnea (e.g., restless sleep)
- Stool habits
- Hearing concerns
Down Syndrome - physical exam
The phenotype is variable from person to person.
- General:
- Short stature
- Hypotonia (80–100%), with an open mouth and a protruding tongue
- Midface hypoplasia
- Head:
- Brachycephaly with a flattened occiput
- Microcephaly
- False fontanel (95%)
- Eyes:
- Upslanting palpebral fissures (98%)
- Inner epicanthal folds
- Brushfield spots (speckling of the iris)
- Fine lens opacities on slit-lamp examination
- Cataracts, refractive error, strabismus, and nystagmus
- Ears:
- Small, prominent, low set; overfolding of upper helix and small canals
- Nose: Small (85%); flat nasal bridge
- Tongue:
- Relative but not true macroglossia (tongue mass is normal)
- Fissuring
- Mouth: High-arched or abnormal palate
- Teeth:
- Missing (50%), small, hypoplastic
- Irregular placement
- Neck:
- In infancy, excess skin at the nape
- Short appearance
- Occasionally webbed
- Heart: Assess for murmur, arrhythmia, cyanosis.
- Abdomen:
- In neonate, distention may be present owing to obstruction or atresia.
- Diastasis recti
- Genitals:
- In adolescents, straight pubic hair
- In males, small penis, cryptorchidism
- Extremities:
- Broad hands, with short metacarpals and phalanges
- 5th finger with hypoplasia of the midphalanx (60%) and clinodactyly (50%)
- Simian crease (single transverse palmar crease) in ~50%. A newborn with a simian crease has a 1 in 60 chance of having Down syndrome.
- Wide gap between the 1st and 2nd toes (96%)
- Syndactyly of 2nd and 3rd toes
- Hyperflexibility of joints
- Skin:
- Cutis marmorata (43%)
- In older children, hyperkeratotic dry skin (75%)
- Fine, soft, sparse hair
Down Syndrome - tests
- EKG: Done within the 1st month of life to rule out cardiac disease
- Auditory brainstem response: Done within the 1st 3 months of life to rule out hearing loss
Down Syndrome - lab
- 2nd-trimester prenatal triple screen test (α-fetoprotein [AFP], unconjugated estriol, and human chorionic gonadotropin [hCG]):
- Performed at 15–18 weeks
- These three serum markers together can detect ~60% of the pregnancies affected by trisomy 21, with a false-positive of ~5%.
- A positive test is an indication for karyotyping with amniocentesis.
- 1st-trimester maternal serum screening (pregnancy-associated plasma protein A and free β-hCG): When these 2 tests are conducted together, it has been shown in multiple studies to have higher sensitivity than 2nd-trimester prenatal screens (91% vs. 70%).
- Chromosomal karyotype on cultured lymphocytes from peripheral blood: May be performed postnatally for confirmation if there is a clinical suspicion of Down syndrome.
- CBC:
- In the newborn period to check for polycythemia and transient myeloproliferative disorder; repeat test in adolescence.
- Down syndrome patients may have an increased mean corpuscular volume (MCV), making the diagnosis of iron deficiency anemia difficult.
- Thyroid function tests: To rule out hypothyroidism or hyperthyroidism
Down Syndrome - imaging
- 1st-trimester ultrasound measurement of nuchal translucency: Performed in the 1st trimester along with maternal serum screening (see “Lab”)
- Fetal ultrasound:
- May show polyhydramnios if bowel obstruction is present
- A thickened nuchal fold, an absent nasal bone in the 1st-trimester, and echogenic intracardiac foci have been associated with an increased risk for Down syndrome.
- Echocardiography and chest radiography: Done in the 1st month of life to rule out cardiac disease
- Lateral cervical spine radiographs in flexion, neutral, and extension: To rule out atlantoaxial instability, defined as >5 mm space between atlas and odontoid process of the axis. Important measures include:
- Atlantodens interval (ADI; normal <4.5 mm): The distance between the posterior surface of the anterior arch of C1 and the anterior surface of the dens
- Neural canal width (NCW; normal ≥14 mm): The distance between the posterior surface of the dens and the anterior surface of the posterior arch of C1
- Distance of subluxation at the occipitoatlantal joint: Normally ≥7 mm
Down Syndrome - diag proced-surgery
- Prenatal karyotyping via amniocentesis (16–18 weeks’ gestation) or chorionic villus sampling (9–11 weeks’ gestation):
- Performed for any woman who presents with a positive triple screen
- May be offered if prenatal ultrasound reveals a finding associated with Down syndrome
- Because this test fails to detect 10–15% of Down syndrome in older women, amniocentesis is typically offered to all women >35 years.
- Tissue sample other than blood (usually skin): To check for mosaicism
Down Syndrome - FOLLOW UP
- Genetic counseling is recommended.
- Many organizations (e.g., Down Syndrome International) are available to families of children with Down syndrome.
Down Syndrome - prognosis
- Life expectancy is mildly decreased, with many living into the 6th decade; median age of death 49 years.
- Alzheimer disease affects ~15% after the 4th decade.
- As adults, most patients with Down syndrome can work in supported positions.
Down Syndrome - complications
- Otitis media with effusion (50–70%)
- Sinusitis
- Tonsillar and adenoidal hypertrophy
- Obstructive airway disease with associated sleep apnea (33–75%), cor pulmonale
- Obstructive bowel disease (12%, newborn period)
- Constipation (owing to low tone and decreased gross motor mobility)
- Subluxation of the hips (secondary to ligamentous laxity)
- Atlantoaxial instability (10–20%; secondary to ligamentous laxity, which is most severe prior to age 10 years)
Down Syndrome - patient monitoring
- Growth and development:
- Specific growth charts for Down syndrome are available.
- Average age for acquiring developmental milestones differs from normal population.
- Late closure of fontanelles
- Consider early intervention program for hypotonia and developmental delay.
- Cardiac:
- Early evaluation in newborn period, with follow-up until the presence or absence of disease is evident.
- Subacute bacterial endocarditis prophylaxis for patients with certain types of cardiac disease.
- Ophthalmologic:
- Early evaluation for cataracts and glaucoma
- Visit to ophthalmologist by 6 months, then every 2 years
- Ear, nose, and throat (ENT)/audiologic:
- Annual audiologic evaluation in the 1st 3 years of life, then every other year
- Orthopedic: Screen for atlantoaxial instability with radiography in preschool years, then every decade; evaluate for atlantoaxial instability prior to participation in contact sports (e.g., Special Olympics)
- Endocrine: Thyroid function tests in newborn period, ages 6 months and 12 months, then yearly
- Use caution with endotracheal intubation if absence or presence of atlantoaxial instability is not known, to avoid spinal cord injury, which may be seen in rare cases.
- Hearing loss may be misinterpreted as a behavioral problem.
- Use care with atropine and pilocarpine for ophthalmologic evaluation because of possible cholinergic hypersensitivity.
Down Syndrome - bibliography
- American Academy of Pediatrics. Health supervision for children with Down syndrome. Pediatrics. 2001;107:442–449.
- Crissman BG, Worley G, Roizen N, et al. Current perspectives on Down syndrome: Selected medical and social issues. Am j Med Genet Part C Semin Med Genet. 2006;142C:127–130.
- Roizen NJ, Patterson D. Down’s syndrome. Lancet. 2003;361:1281–1289.
- Rosen T, D’Alton ME. Down syndrome screening in the first and second trimesters: What do the data show? Semin Perinatol. 2005;29:367–375.
- Vachon L, Fareau GE, Wilson MG, et al. Testicular microlithiasis in patients with Down syndrome. J Pediatr. 2006;149:233–236.
Down Syndrome - CODES
Down Syndrome - icd9
758.0 Down syndrome
Down Syndrome - FAQ
- Q: Why was Down syndrome referred to as mongolism in the past?
- A: There was a mistaken notion about a racial cause for this syndrome because of the facial appearance, which was thought to be similar to that of those of Mongoloid origin.
- Q: Do all children with Down syndrome have mental retardation?
- A: No. Though all persons with nonmosaic Down syndrome have some degree of cognitive disability, some have IQs >70 and are not considered to have mental retardation.
- Q: Can a normal cardiac examination rule out the presence of a cardiac anomaly?
- A: No. The American Academy of Pediatrics recommends that all patients with Down syndrome have a cardiology consultation within the first month of life. Timely surgery may be necessary to prevent serious complications.
- Q: Are patients with atlantoaxial instability symptomatic?
- A: No. Most are asymptomatic, but symptoms of cord compression may be seen in 1–2% of patients.
- Q: I have seen growth charts for Down syndrome patients that allow for plotting of lengths, heights, and weights. Are there special growth charts available for plotting head circumference?
- A: Yes. If appropriate growth charts are not used for plotting head circumference, head growth may appear abnormal. Head circumference growth charts are available through the Internet: http://www.growthcharts.com
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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