#126: Understanding the Extra Chromosome: Trisomy 21

November 20, 2024 | By Sam Masur

Audio

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. 

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. 

Disparities in Tx/Evaluation:

In general, compared to other children with special healthcare needs, children with Down syndrome are less likely to have private insurance, less likely to have a medical home and more likely to have unmet needs for support services.

Black people with Down syndrome have been shown to face even greater disparities when it comes to mortality than those observed in the general population; these disparities begin as early as infancy (Yang, 2002).

Evaluations and Screenings For Toddler/School-Age Children:

• Hearing: For a child who passed the initial newborn hearing screen, rescreen at 6 months.  Behavioral audiogram and tympanometry should then be performed every 6 months with an audiologist until normal hearing levels are established bilaterally (usually after age 4).
• Thyroid: Test TSH annually. If subclinical hypothyroidism (high TSH with normal T4), check anti-thyroid Abs – if detected, measure TSH every 6 months.
• Iron deficiency: Measure CBC and iron studies annually.  Patients with Down syndrome have similar risk of iron deficiency anemia as the general population but might be missed due to macrocytosis.
• Growth: Track regularly on a Down syndrome-specific growth chart.
• Celiac disease: Routine screening is not advised. Obtain TTG with quantitative IGA in any patients with symptoms, such as diarrhea, protracted constipation, unexplained failure to thrive, anemia, abdominal pain, or refractory developmental/behavioral problems.
• Sleep apnea: Obtain a sleep study in all children by ages 3-4. A study should be ordered sooner for children with signs of sleep disordered breathing includes snoring, restless sleep, apneic pauses
• Cardiac: Obtain an echocardiogram for any new cardiac exam findings.
• Vision: Refer to ophthalmology by 6 months of life. In children with normal vision, obtain an annual vision screen by photoscreening – refer to ophthalmology if this is abnormal or unavailable. 
• Neurology: Monitor for signs of acute regression; refer to neurology if present.
• Dental: Attend regular 6 month dental visits

Management in Teenagers 

Sports Screening:

The pediatrician should evaluate for any signs and symptoms of spinal cord injury that could be related to atlanto-axial instability, including loss of motor skills, loss of bowel or bladder control, neck pain or neck stiffness. The provider should caution patients about participation in contact sports such as football, soccer and gymnastics, and as well as regarding trampoline use. No screening X-rays should be done for asymptomatic patients. For a patient with a stable cardiac lesion (e.g, small ASD), they should follow up with the cardiologist for any sports clearance concerns.

GU System – Puberty:

It’s important to start to discuss menarche and associated  symptoms early. It is also important to talk about pregnancy as well as provide information regarding the  chance of having a child with Down syndrome.

Transition to Adult Care:

Transitioning the medical home from pediatric to adult care includes preparing the family, medical record and medications. 

It is important to discuss independent living opportunities such as group homes and opportunities for further education and community-supported employment. In addition, bringing up the topic about guardianship is also important. 

Resources

AAP Health Supervision for patients with Down Syndrome

National Down Syndrome Society | NDSS

Goal

Listeners will become familiar with the basic genetics and clinical features of Down syndrome, as well as the screening and management of patients with Down syndrome from newborn to young adult.

Learning Objectives

After listening to this episode listeners will…  

1. Recall the basics of the genetics and clinical manifestations of Down syndrome. 
2. Be familiar with multisystem examination and screening in the newborn period and beyond.
3. Recognize the importance of prompt referral to early intervention services 
4. Learn about the multidisciplinary approach to managing a patient with Down syndrome 
5. Feel comfortable providing anticipatory guidance for all teenagers with Down syndrome.

Disclosures

Dr. Keppler reports no relevant financial disclosures. The Cribsiders report no relevant financial disclosures. 

Citation

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.