Approach to a child with Down syndrome (trisomy 21): Clinical sciences

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Introduction0:00–0:24

Down syndrome, or trisomy 21, is a genetic condition most commonly associated with an extra copy of chromosome 21. The health and quality of life for children with Down syndrome can be optimized with medical surveillance, family and community support, and early intervention services.

Focused H&P0:24–1:14

If a pediatric patient presents with a chief concern suggesting Down syndrome, first obtain a focused history and physical exam.
These patients may have been identified with prenatal screening, and the biological mother might be of advanced maternal age, which is a risk factor for chromosomal nondisjunction.
Physical exam reveals classic facial features, like upslanting palpebral fissures, epicanthal folds, a flat facial profile, and low-set small ears.
Patients also have a short neck with excessive skin folds at the nape; a single palmar crease; and an unusually wide space between the first and second toes on their feet called a sandal toe gap.
Finally, you’ll typically see generalized hypotonia, significant head lag, and a weak moro reflex. With these findings, consider Down syndrome and order a karyotype.

Down syndrome1:14–2:14

If it reveals trisomy of chromosome 21, diagnose Down syndrome. Here’s a clinical pearl!
In most cases, Down syndrome is caused by nondisjunction, which results in an extra copy of chromosome 21. However, it can also be caused by mosaicism, where some cells have 2 and others 3 copies of chromosome 21; or translocation, where part of chromosome 21 becomes attached to another chromosome.
When a parent carries a balanced translocation, their children can acquire extra genetic material from chromosome 21, resulting in an unbalanced translocation.
This form of Down syndrome carries a higher risk of recurrence compared to nondisjunction and mosaicism. Because all forms of Down syndrome can present with a similar phenotype, it's important to perform genetic testing and offer genetic counseling, to determine the potential recurrence risk.

Neonatal health supervision/Universal screening2:14–4:19

After confirming the diagnosis, initiate neonatal health supervision to assess for common conditions associated with Down syndrome.
Complete this before your patient is discharged from the hospital. Start with universal screening, which includes testing that’s recommended for all newborns with Down syndrome.
First, assess for congenital heart defects. It’s important to screen all patients with an echocardiogram, since nearly half have congenital heart defects.
The echo often reveals an intracardiac structural abnormality with a left-to-right shunt, such as an atrioventricular septal defect, which confirms the presence of a congenital heart defect.
While atrioventricular septal defect is the most common congenital heart lesion in patients with Down syndrome, you might identify atrial or ventricular septal defects, patent ductus arteriosus, or tetralogy of Fallot.
Next, assess for congenital hypothyroidism by ordering thyroid-stimulating hormone, or TSH, and free thyroxine, or free T4, levels.
If TSH is high and free T4 is low-to-normal, diagnose congenital hypothyroidism. Finally, assess for hematologic disorders by ordering a CBC with a peripheral smear.
You might see an elevated hemoglobin and hematocrit, indicating polycythemia; or elevated mean corpuscular volume, indicating macrocytosis.
Both are common findings that may persist throughout early childhood without causing symptoms. Additionally, look for blasts on the peripheral smear.
Blasts are often the first sign of transient abnormal myelopoiesis, or TAM for short, which is a blood disorder that occurs exclusively in newborns with Down syndrome.
While TAM can be asymptomatic, it increases the patient’s lifetime risk of leukemia, so advise caregivers to watch for concerning signs like recurrent fevers or easy bruising.
Any of these lab abnormalities indicate the presence of a hematologic disorder. After you’ve finished screening your patient, perform a symptomatic evaluation, where assessment depends on relevant clinical findings.

Symptomatic evaluation and GI anomaly4:19–5:26

For example, you might find poor feeding, vomiting, or choking during feeds; and some infants may have failed to pass meconium.
The prenatal ultrasound might also have detected a gastrointestinal defect, like duodenal or anorectal atresia. In this case, consider a structural gastrointestinal anomaly, since patients with Down syndrome are at an increased risk for these conditions.
Next, place a nasogastric tube and order chest and abdominal X-rays. The X-rays may show the nasogastric tube coiling within a blind esophageal pouch, suggesting esophageal atresia, which is often accompanied by a tracheoesophageal fistula.
On the other hand, X-ray might reveal a double bubble sign, where the stomach and duodenum are distended, suggesting duodenal atresia; or it may reveal a dilated proximal colon, suggesting Hirschsprung disease.
These findings indicate the presence of a structural gastrointestinal anomaly. Let’s move on to pediatric health supervision, starting with universal screening that occurs during well-child visits.

Pediatric health supervision/Universal screening with well-child visits5:26–5:40

Here, you should monitor for common health conditions associated with Down syndrome that might appear during childhood. Let’s start by assessing for ophthalmologic problems.

Vision problems5:40–6:15

These patients have an increased risk of congenital cataracts, which can be identified within the first few months of life.
Check the red reflex during each well-child visit, and perform regular vision screening. An asymmetric red reflex suggests strabismus or amblyopia; while an absent, black, or white red reflex suggests cataracts.
Finally, vision screening may reveal impaired vision or myopia. These findings indicate an ophthalmologic problem.

Hearing problems6:15–6:40

Now, middle ear abnormalities and hearing loss occur frequently in Down syndrome. So, continuously assess for otologic problems, by examining the ears with an otoscope and performing frequent hearing screens.
You might find a stenotic ear canal, middle ear effusion, or otitis media; and the hearing screen may confirm hearing loss.
Any of these findings indicate an otologic problem. Next, assess your patient’s pattern of weight gain.

Weight gain6:40–7:23

Children with Down syndrome tend to have short stature, with weight gain outpacing linear growth. For this reason, monitor the weight, height, and weight-for-height trends using a Down syndrome-specific growth chart, which can help you determine if the patient has overweight or obesity.
Here’s a clinical pearl! Determining the caloric intake for a child with Down syndrome is not an easy task.
Some of them might have conditions requiring increased caloric intake like congenital heart disease or pulmonary hypertension.
However, if your patient doesn’t have any of these conditions, they will need a lower caloric intake at baseline than children without Down syndrome.

Neuropsychosocial impacts7:23–7:58

Finally, assess for any neuropsychosocial impacts by performing developmental surveillance. Most children with Down syndrome have mild to moderate intellectual disability and demonstrate significant developmental delay, which may impact their social, educational, and vocational opportunities.
These children can have coexisting psychiatric or behavioral disorders like attention-deficit hyperactivity disorder, autism spectrum disorder, or aggressive behaviors.
Any of these conditions indicate a significant neuropsychosocial impact. Okay, let’s talk about screening labs and procedures.

Screening labs and procedures/Acquired hypothyroidism7:58–8:27

First, assess for acquired hypothyroidism by checking TSH and free T4 levels annually. If TSH is high and free T4 is low-to-normal, diagnose acquired hypothyroidism.
Here’s a clinical pearl! You can suspect acquired hypothyroidism based on physical exam findings if there is a drop in linear growth with increased weight gain.
Now, you should routinely assess for hematologic disorders, since children with Down syndrome have an increased risk of leukemia and iron deficiency anemia.

Hematologic disorder8:27–9:09

Order an annual CBC with peripheral smear, as well as serum iron, ferritin, and total iron binding capacity, or TIBC. CBC might demonstrate elevated white blood cells and blasts, which could indicate leukemia.
Additionally, you may see low hemoglobin and hematocrit, with low-to-normal MCV for age; and low serum iron, low ferritin, and high TIBC levels, indicating iron deficiency anemia.
Any of these lab abnormalities point to a hematologic disorder. Lastly, assess for disordered sleep between ages 3 and 4 years old.

Disordered sleep9:09–9:40

Because it might be present without clinical symptoms, obtain a sleep study or polysomnogram, and if abnormal, diagnose a sleep disorder.
Here’s a clinical pearl! While we screen at ages 3 to 4, you should still ask about symptoms of disordered sleep at each well-child check, noting that children with Down syndrome who have disordered sleep often respond well to iron supplementation.

Symptomatic evaluation/Dysphagia9:40–10:03

Alright, let’s move on to symptomatic evaluation. If the patient presents with poor feeding, coughing or choking during feeds, or poor weight gain, consider dysphagia, which is commonly seen in infants with Down syndrome due to hypotonia.
Next, order a swallow study, and if it demonstrates aspiration, diagnose dysphagia. Next, if your patient has diarrhea or constipation, slow growth or growth faltering, and abdominal pain or bloating, consider celiac disease.

Celiac Disease10:03–10:33

Then, obtain a tissue transglutaminase immunoglobulin A, or TTG IgA, and a quantitative IgA level. If the TTG IgA is positive, and the quantitative IgA is normal, the patient likely has celiac disease.
You can obtain an endoscopy with biopsy to confirm the diagnosis. Some patients exhibit snoring, restlessness or gasping during sleep, or excessive daytime sleepiness, which point to obstructive sleep apnea, or OSA for short.

Obstructive sleep apnea10:33–11:05

OSA is common among young children with Down syndrome, due to their small upper airway, low muscle tone, and increased incidence of overweight and iron-deficiency anemia.
To evaluate, order a sleep study. If you detect episodes of decreased airflow with oxygen desaturation during sleep, diagnose obstructive sleep apnea.

Atlantoaxial instability11:05–12:09

Finally, if your patient develops new onset neck pain, sudden loss of motor skills, or loss of bowel or bladder control, consider atlantoaxial instability.
In patients with Down syndrome, ligamentous laxity between the C1 atlas and C2 axis cervical vertebrae increases the risk of spinal cord injury during cervical spine hyperextension or hyperflexion.
For this reason, they should avoid activities that increase the risk of spinal cord injury, like contact sports and trampolines.
To evaluate, order a cervical spine X-ray to assess the atlas and axis. Dislocation of the atlas relative to the dens of the axis confirms atlantoaxial instability.
Here’s one more clinical pearl! There is significant manipulation of the cervical spine during anesthesia and intubation.
If a patient with Down syndrome needs anesthesia or surgery, get a cervical spine X-ray, or have the child cleared by a neurosurgeon.

Review12:09–12:57

Alright, as a quick recap… All infants with Down syndrome should receive neonatal health supervision and screening for congenital heart defects, congenital hypothyroidism, and hematologic disorders, as well as symptomatic evaluation for structural GI anomalies.
Similarly, all children with Down syndrome should receive universal screening for developmental concerns, such as ophthalmologic and otologic problems, overweight and obesity, and neuropsychosocial impacts.
Finally, obtain annual blood tests to screen for acquired hypothyroidism and hematologic disorders, as well as studies for disordered sleep; and perform symptomatic evaluation for dysphagia, celiac disease, obstructive sleep apnea, and atlantoaxial instability.
Approach to a child with Down syndrome (trisomy 21): Video | Osmosis