Today, I review, link to and embed The Cribsiders’ #126: Understanding the Extra Chromosome: Trisomy 21.*

*Keppler H, Venkataraman V, Engel S, Berk J, Chiu C, Masur S. “#126: Understanding the Extra Chromosome: Trisomy 21. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ November 20, 2024.

All that follows is from the above resource.

Summary:

Taking care of patients with Down Syndrome requires a careful and multidisciplinary approach. Come and join us with our wonderful guest, Dr. Hannah Keppler, as we go over everything you need to know about managing patients with Down Syndrome in a primary care setting. In this episode, we go over what to look out for during an initial newborn evaluation of a baby with Trisomy 21, the important screening tests and specialist care involved, and why we don’t get routine screening X-rays for atlantoaxial instability.

Trisomy 21 Pearls

1. About 50% of patients with Trisomy 21 have some sort of congenital heart disease, so a thorough initial cardiac evaluation as well as close follow-up is required
2. When tracking growth of patients with Trisomy 21, it is important to use the Trisomy 21 specific growth chart. In the first 2 years, children with Down syndrome are usually underweight and after age 3 they are usually overweight when compared to children without Down syndrome.
3. It is important to refer to developmental services as early as possible
4. Screening imaging for atlantoaxial instability is not recommended for asymptomatic patients with Trisomy 21
5. Transitioning from pediatric to adult care, as well as involvement in the community (education, jobs), is important to bring up promptly during adolescent visits

Trisomy 21 Notes

Definitions and Genetics 

Trisomy 21 is a genetic disorder characterized by 3 copies of chromosome 21. It’s the most common chromosomal abnormality among liveborn infants. This can include a wide range of medical conditions encompassing many different organ systems, as well as varying degrees of cognitive impairment.

Genetics Overview

• The majority of cases of trisomy 21 are sporadic.
• In 3-4% of cases,  the extra chromosomal material is from an unbalanced translocation between 21 and another chromosome
• In 1-2% of cases there are a mix of two cell lines causing mosaicism; these people are usually more mildly affected.

Prenatal Screening

ACOG recommends that all pregnant patients be offered screening for Down syndrome. The newer and more common screening test is the NIPT (Non-invasive testing with cell free DNA),which is the most sensitive and specific screening method. It can be performed as early as 9-10 weeks gestation. However, this is not diagnostic, therefore a high risk NIPT result requires confirmatory testing with amniocentesis or chorionic villus sampling

Newborn Management

Initial Exam Findings

An important finding on the initial exam is hypotonia.

There are also distinct facial features that may be present in a neonate with trisomy 21:

• Small head
• Epicanthal folds
• Flat nasal bridge
• Upslanting palpebral fissures
• Small mouth
• Single transverse palmar crease

Some common extremity findings:

• Short fifth finger
• Wide spacing between the first and second toe with deep plantar groove
• Short broad hands

Common skin finding include:

• Cutis marmorata, which looks like mottled, fishnet like blotches in the skin

Patients with Down syndrome have an increased risk of congenital heart disease. Therefore, any signs of hypoxia, respiratory distress, or signs of heart failure require urgent transfer to NICU. In addition, any concerns for duodenal atresia, anal atresia or Hirschprung’s (bilious emesis, no passage of meconium, etc), or significant feeding problems require urgent transfer.

Evaluation in the First Newborn Visits

Cardiovascular Evaluation

Half of children with Down syndrome have some kind of congenital heart disease. Most common is complete AV septal defect, followed by ASD and VSD. A quarter have more than one defect. Echo is normally done in the nursery; during the newborn visit, assess the echo read by the pediatric cardiologist and coordinate with the cardiologist as needed.

Weight Gain and Feeding Evaluation

Feeding problems are extremely common in babies with Down syndrome. Breastfeeding can be a challenge due to anatomy, so if a parent wants to breastfeed, close work with a lactation consultant is important. Very close follow-up with growth and weight gain is important during the newborn phase. There is a Down syndrome specific growth curve which takes into account weight and stature differences in this population, including an increased likelihood to have a lower weight in the first two years, higher weight in the later years and a general shorter stature.

Dysphagia, aspiration, and reflux is common among patients with Down syndrome. The primary care clinician should evaluate for and address signs of dysphagia, including coughing and choking with feeds, which may also be due to hypotonia  or poor tongue control. Many patients with DS have silent aspiration, and might not have choking or coughing. If you notice a weak cough or poor feeding during the visit, they should be referred for a feeding evaluation, which may include videofluoroscopic swallow studies.

Hearing Evaluation 

Hearing loss, especially congenital hearing loss, is very common in patients with Down syndrome. Close analysis of the Newborn hearing screen is essential.

• If baby PASSES newborn hearing screen – repeat hearing screen at 6 months of age
• If baby DOES NOT PASS newborn hearing screen – prompt referral to ENT

Middle ear disease is very common in older patients as well, due to the increased risk of stenotic canal.

Eye Evaluation

There is a significant increased risk of congenital cataracts (5%) in patients with Down syndrome. They also have an increased risk of strabismus, nasolacrimal duct obstruction, glaucoma, and nystagmus. Therefore, in addition to regular eye exams at the general pediatrician, babies with Down syndrome should see ophthalmology within the first 6 months.

Endocrinological Evaluation:

There is a 2-7% risk of congenital hypothyroidism. As a result pediatricians should obtain a TSH in newborns if it is not a part of the newborn screen). For children with a normal newborn TSH,  repeat TSH at 6 and 12 months of age and then annually

Hematological Evaluation

It is recommended to get a CBC with differential by day 3 of life to evaluate for transient abnormal myelopoiesis (formerly transient myeloproliferative disorder) and polycythemia.

TAM is identified by the presence of blasts on peripheral smear and is associated with an increased risk of acute myeloblastic leukemia within the first 2 years of life. If blasts are seen, urgent referral to a pediatric hematologist/oncologist is needed. Even if babies do not have TAM, there is an increased risk of leukemia.

Other hematologic abnormalities such as neutropenia, thrombocytopenia, thrombocytosis are also common and generally resolves. The one exception to this is macrocytosis, which generally doesn’t resolve.

Other Evaluations:

Renal and urinary tract abnormalities have been reported at increased frequency in down syndrome; routine screening is not recommended, but clinicians should be aware of next steps for any prenatal findings.

Thorough neurologic assessment is essential due to an increased risk for seizures and infantile spasms in patients with down syndrome.

There is an increased risk of obstructive sleep apnea; clinicians should discuss symptoms of OSA with families  at least once during the first 6 months.*

* Obstructive sleep apnea in children with down syndrome – Prevalence and
evaluation of surgical treatment [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Int J Pediatr Otorhinolaryngol. 2020 Jun:133:109968. doi: 10.1016/j.ijporl.2020.109968. Epub 2020 Feb 26.

There are 931 similar articles in PubMed.

The above article has been cited by 13 articles in PubMed.

Management in Toddler – School Age Patients

Early Development:

In down syndrome, developmental impairment usually becomes apparent within the first year of life.  Prompt connection with Early Intervention is very important to establish patients with the proper therapies needed for development.

Autism, ADHD, and other psychiatric or behavioral problems including disruptive disorders and oppositional disorder are all common in children with Down syndrome. The diagnosis of autism can often be delayed. Children with Down syndrome should be screened for autism between 18 and 24 months (same as other children) and referred for specialty evaluation as needed.