Down's Syndrome

Swati Kolpuru
Consultant Pediatrician, USA
First Created: 12/24/2001 

Neonatal Features

Many fetuses with Down's syndrome are now prenatally diagnosed by karyotyping done because of advanced maternal age or abnormal triple screen test or fetal ultrasonographic findings.

If not prenatally diagnosed, most patients with Down syndrome are usually recognized at birth owing to characteristic physical findings. Common neonatal features include:

  • Rounded head
  • Third fontanelle
  • Brachycephaly
  • Fine, soft and sparse hair
  • Upslanted palpebral fissures
  • Epicanthal folds
  • Brushfield spots
  • Spoke-like appearance of the retinal vasculature
  • Midfacial hypoplasia
  • Flattened nasal root
  • Small dysplastic pinnae
  • Large tongue in a small mouth
  • Short neck
  • Transverse palmar creases
  • Brachydactyly
  • Fifth-finger clinodactyly
  • Wide gap between the first and second toe
  • Diastasis recti
  • Hypotonia
  • Poor neck retraction response
  • Poor or absent Moro's reflex
  • Small penis (male) or labial index sign (female)

Specific Medical Concerns in Newborns

Life-threatening conditions diagnosed in a newborn with Down syndrome include:

Congenital heart disease: Congenital heart disease represents the most common cause of death in childhood. The cardiac defects that can occur are:

  • Endocardial cushion defect
  • Ventricular septal defect
  • Patent ductus arteriosus
  • Atrial septal defect
  • Tetralogy of Fallot

Diagnosis of cardiac disease in infants with Down syndrome is not always obvious; in fact, clinical examination in the newborn period may be entirely normal. The alerting signs are poor feeding, easy fatigability, dyspnea, diaphoresis, cyanosis, and cardiac murmur. However, some infants are asymptomatic if they are not experiencing congestive cardiac failure. Therefore, an infant with Down syndrome needs careful evaluation by current techniques such as echocardiography, Doppler flow analysis, etc.

Congenital gastrointestinal disease: Duodenal obstruction occurs more frequently in infants with Down syndrome. The infant may present with bile stained vomiting, abdominal distension, and a visible peristaltic wave. A "double bubble sign" characterizes the abdominal radiograph. The obstruction may be caused by congenital atresia, intrinsic stenosis, or extrinsic stenosis secondary to annular pancreas or malrotation of the bowel with bands. In the neonatal period, these lesions may constitute surgical emergencies. Other malformations that can occur are:

  • Hirschsprung disease
  • Esophageal atresia
  • Pyloric stenosis
  • Diverticulum of the stomach
  • Malrotation of the bowel

Hematological disease:
The incidence of leukemia is higher in infants with Down's syndrome. Other disorders described in newborns include:

  • Polycythemia
  • Thrombocytopenia
  • Erythroblastosis fetalis

Ophthalmologic problems: Nystagmus and strabismus occur frequently in the newborn period and require a consultation to rule out corneal opacities. Other ocular problems seen are:

  • Refractive error
  • Blepharoconjunctivitis
  • Cataracts
  • Keratoconus
  • Retinal pathology
  • Optic nerve hypoplasia

An abnormality detected on physical examination or poor visual tracking requires further investigation.

Urogenital abnormalities: These include:

  • Micropenis
  • Cryptorchidism
  • Hypospadias
  • Anomalies of the kidneys and ureters

Endocrine abnormalities:
Persistent primary congenital hypothyroidism commonly occurs in newborns with Down syndrome. Thus, thyroid screening which is so important for all infants is particularly relevant for infants with Down syndrome.

Ear problems:
There is an increased incidence of congenital sensorineural hearing loss in children with Down's syndrome, so a hearing screen is recommended before discharge. Middle ear effusions may also be present.

Cardinal Features in Neonates

  • Poor Moro reflex (85%)
  • Hypotonia (80%)
  • Flat facial profile (90%)
  • Upslanted palpebral fissures (80%)
  • Abnormal ears (60%)
  • Excess skin on the back of the neck (80%)
  • Transverse palmar crease (45%)
  • Hyperextensible joints (80%)
  • Dysplasia of pelvis (70%)
  • Fifth finger clinodactyly (60%)

Six or more of the above features should be present for making a diagnosis clinically. Sometimes the findings may be subtle and maybe missed. Also, the findings can be confounded by prematurity or ethnicity.

Important Steps after Suspecting Down Syndrome in a Neonate

  • Establish diagnosis
  • Thorough clinical examination to observe for congenital heart disease or gastrointestinal malformation
  • Inform the parents in a supportive way

Laboratory orders:

  • Chromosomal karyotype
  • Thyroxine
  • TSH
  • Complete blood count
  • Differential count
  • Platelet count
  • Nucleated RBC count
  • Echocardiography
  • Hearing screen
  • Funduscopy

Discuss the diagnosis and management plan with parents. Refer parents to an infant intervention program and to a support group. Conduct a follow-up meeting with the family.

Screening Recommendations

Neonatal period (Birth to one month):

  • Chromosomal karyotype
  • Hematocrit or complete blood count to rule out myeloproliferative disorders
  • Thyroid function tests
  • Echocardiogram
  • Auditory brainstem response or otoacoustic emission test to assess congenital sensorineural hearing at birth or by 3 months of age.
  • Ophthalmologic evaluation if nystagmus or strabismus

Infancy (1-12 months):

  • Echocardiogram if not done in the newborn period
  • Auditory brainstem response test if previous results are suspicious.
  • Ophthalmologic evaluation by six months of age.
  • Thyroid function test at 6 and 12 months of age.

Childhood (1 year to 12 years):

  • Echocardiogram if not done previously.
  • Thyroid function test yearly.
  • Regular eye exams yearly if normal, or more frequently as indicated.
  • Between 3 and 5 years of age, lateral cervical spine x-rays to rule out atlantoaxial instability.
  • Dental evaluation at one year of age and follow-ups every six months.
  • Celiac disease screening with IgA antiendomysium antibodies and total IgA at 2-3 years of age.

Adolescence (12 to 18 years):

  • Pelvic exam if sexually active.
  • Thyroid function testing yearly.
  • Hearing and vision evaluation every year.
  • Repeat cervical spine x-rays if needed.
  • Echocardiogram if evidence of valvular disease on clinical exam.

Adults (over 18 years):

  • Annual thyroid screening.
  • Ophthalmologic evaluation every 2 years.
  • Repeat cervical spine x-rays as needed.
  • Auditory testing every 2 years.
  • Twice yearly dental visits.
  • Pap smears every 1-3 years following the age of first intercourse.
  • For women who are sexually not active, finger- directed cytology exam.
  • Screening pelvic ultrasound every 2-3 years for women who refuse or have inadequate follow -up bimanual examinations.
  • Yearly breast examination.
  • Mammography after age 50.

Prenatal Screening

Because of the morbidity associated with Down syndrome, screening, and diagnostic testing for this condition are offered as optional components of prenatal care. Prenatal diagnosis of trisomy 21 allows parents the choice of continuing or terminating an affected pregnancy.

The incidence of fetal trisomies is directly related to maternal age. The risk of having a child with Down syndrome increases in a gradual, linear fashion until about age 30 and increases exponentially thereafter2. The risk of having a child with Down syndrome is 1/1300 for a 25-year old woman; at age 35, the risk increases to 1/365. At age 45, the risk of having a child increases to 1/30.


If a patient has had a trisomy 21 pregnancy in the past, the risk of recurrence in a subsequent pregnancy is still highly dependent on maternal age. If the previously affected pregnancy was a chromosome-21 translocation the recurrence risk is high enough to dwarf the age-specific risk at most ages.

Maternal serum screening: Maternal serum screening can allow the detection of trisomy 21 pregnancies in women younger than 35 years who give birth to about 70 percent of infants with Down syndrome. The serum markers most widely used are:

  • Alfa-fetoprotein
  • Unconjugated estriol
  • Human chorionic gonadotropin
  • Inhibin A

This combination is known as "quadruple test" or "triple test" (without Inhibin A). The maternal serum levels of these proteins and of steroid hormones vary with the gestational age for the pregnancy. These tests are usually performed at 15 to 18 weeks of gestation. The level of each serum marker is measured and reported as a multiple of the median for women with pregnancies of the same gestational age as that of the patient's. The likelihood of trisomy 21 is calculated on the basis of each of the serum marker results and the patient's age. A positive test is an indication for amniocentesis.

The triple test can detect 60 percent of trisomy 21 pregnancies; it has a false-positive rate of 5 percent. The likelihood of a fetus having trisomy 21 in a patient with a positive test is about 2 percent. A normal result reduces the likelihood of trisomy 21 but does not exclude it. Test performance can be slightly improved by adjusting for maternal weight, ethnic group, and insulin-dependent diabetes mellitus. The triple test fails to detect 10 to 15 percent of trisomy 21 pregnancies in the older age group. Therefore for women 35 years or older, maternal serum screening should not be offered as an equivalent alternative to amniocentesis or chorionic villus sampling. Several demographic or pregnancy-related factors influence biochemical levels. Taking these factors into account will enhance screening performance. The factors are:

  • Gestational age
  • Maternal weight
  • Maternal race
  • Maternal insulin-dependent diabetes
  • Multiple fetal pregnancies
  • Family history of Down syndrome

Ultrasound Assessment:
An estimate of gestational age by ultrasonography improves the performance of the triple or quadruple test. Second-trimester ultrasound assessment may be helpful for predicting the likelihood of trisomy 21 in pregnancies at increased risk. Ultrasonographic findings associated with fetal Down syndrome:

  • Increased nuchal fold thickness >5 mm
  • Intrauterine growth restriction
  • Mild cerebral ventriculomegaly
  • Brachycephaly
  • Flat facies
  • Small ears
  • Choroid plexus cysts
  • Cystic hygromas
  • Echogenic intracardiac foci
  • Congenital heart defects
  • Ventricular septal defect
  • Atrioventricular canal
  • Tetralogy of Fallot
  • Bright papillary muscle
  • Increased intestinal echogenicity
  • Duodenal atresia ("double -bubble sign") after 22 weeks' gestation
  • Renal pelvis dilation
  • Shortened humerus and femur
  • Increased iliac wing angle
  • Incurving (clinodactyly) and hypoplasia of the fifth finger
  • Increased space between first and second toes
  • Two-vessel umbilical cord
  • Non-immune hydrops
  • Possible increased biparietal diameter-femur length ratio

FIRST-TRIMESTER SCREENING: First-trimester screening by means of maternal age and measurement of nuchal translucency could provide a trisomy 21 detection rate of 63 percent, with a 5 percent false-positive rate. Combining this with measurement of maternal serum free beta-hCG subunit and pregnancy-associated protein A could increase the detection rate to 80 percent, at the same false-positive rate.

Definitive prenatal diagnosis of trisomy 21 requires cytogenetic analysis of cells obtained by one of the three invasive procedures:

  • Chorionic villus sampling
  • Early amniocentesis
  • Second-trimester amniocentesis

Chorionic villus sampling (CVS) and early amniocentesis are the primary diagnostic procedures used between 11 and 14 weeks gestation. The risks of amniocentesis include

  • Rare puncture of the fetus
  • Bleeding
  • Infection
  • Isosensitization
  • Neonatal respiratory distress syndrome
  • Neonatal pneumonia

The risk of CVS include:

  • Limb reduction defects
  • Bleeding

However, if CVS is done at 10 weeks or later the incidence of fetal defects is reduced.

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Down's Syndrome Down's Syndrome 2001-12-24
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