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

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.

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. 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.

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.

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. 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. 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.

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. 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.