Do you have a child with Down syndrome or know someone who has Down syndrome? People with Down syndrome are predisposed to having physical and cognitive challenges. 

We know that it can be difficult to find information about Down syndrome and we would like to help provide educational material.

As part of the background for this blog post, the scientific literature was searched for information. Additionally we looked online for frequently asked questions so we could answer them.

This blog post provides several illustrations and helpful information.

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Why is Trisomy 21 called Down syndrome?

In 1862 a physician named Dr. John Langdon Down published on the condition that is currently called Down syndrome or Trisomy 21.[1]

This is a younger boy with Down syndrome. CamachoMD
This is a younger boy with Down syndrome.

What is Down syndrome?

The human body is made up of genetic material that codes for various tissues and physical features.[2]

Deoxyribonucleic acid (DNA) is the building block for genetic material and is found in chromosomes that are located in the nucleus of the cells found throughout our bodies.

DNA Encoding for Human with CamachoMD
DNA Encoding for Human.

There are 23 pairs of chromosomes in humans that are inherited from the parents (23 chromosomes from the mother and 23 chromosomes from the father).

DNA and chromosomes in Down syndrome. CamachoMD
DNA and chromosomes in Down syndrome.

Down syndrome is a disorder in which a child is born with an additional complete chromosome 21 or part of an additional chromosome 21.

Twenty three chromosomes. The chromosomes pairs are labeled. CamachoMD
Twenty three chromosomes. The chromosomes pairs are labeled.

Three copies of chromosome 21 are why Down syndrome is also known as Trisomy 21 (“tri” = three, “somy” = presence of chromosomes).

What causes Down syndrome?

Non-disjunction

Non-disjunction is when either the father’s sperm or the mother’s egg has an extra chromosome 21 (two chromosomes instead of one).

Sperm and eggs in Down syndrome. Note that the sperm has 2 copies of chromosome 21 and the egg has one copy of chromosome 21. So, when they combine, there will be 3 copies of chromosome 21 (leading to Trisomy 21). CamachoMD
Sperm and eggs in Down syndrome. Note that the sperm has 2 copies of chromosome 21 and the egg has one copy of chromosome 21. So, when they combine, there will be 3 copies of chromosome 21 (leading to Trisomy 21).

So, when the mother or father passes on their two copies of chromosome 21, the final outcomes is that the child will end up having three copies of chromosome 21.

Chromosomes in Down syndrome, note there are three of the Chromosome 21 (Trisomy 21). CamachoMD
Chromosomes in Down syndrome, note there are three of the Chromosome 21 (Trisomy 21).

Non-disjunction is the cause in 94-95% of children with Down syndrome.[3]

Translocation

Translocation is when a partial or complete copy of chromosome 21 attaches itself to another chromosome (often chromosome 14) and this can also lead to Down syndrome.

Down syndrome translocation. Part of chromosome 21 from one of the parents chromosome attached itself to chromosome 14 (most common translocation) and now the child has extra genetic material from chromosome 21. The green arrow points to the extra material. CamachoMD
Down syndrome translocation. Part of chromosome 21 from one of the parents chromosome attached itself to chromosome 14 (most common translocation) and now the child has extra genetic material from chromosome 21. The green arrow points to the extra material.

Translocation is seen in approximately 4-5% of children with Down syndrome.[4]

Mosaicism

Mosaicism is when some cells in the children with Down syndrome have 46 chromosomes and some of them have 47 chromosomes, and this occurs in about 1% of children with Down syndrome.

Mosaicism in Down syndrome. Note that some of the cells have 46 chromosomes and some of them have 47 chromosomes (shown in red). CamachoMD
Mosaicism in Down syndrome. Note that some of the cells have 46 chromosomes and some of them have 47 chromosomes (shown in red).

How common is Down syndrome?

It is estimated that one in 700 to one in 1000 children born has Down syndrome.[5]

Pregnant woman with a blue shirt. CamachoMD
Pregnant woman.

Down syndrome is more likely to occur in the children of mothers who are over the age of 40, however, because more women of younger age represent the majority mothers giving birth, the majority of children who have Down syndrome are actually born to mothers who are in their 20s and 30s. [6]

  • The estimates for the maternal age-specific live birth prevalence of Down syndrome[6] are as follows:
    • 20-year-olds = 1 in 1441
    • 25-year-olds = 1 in 1383
    • 30-year-olds = 1 in 959
    • 35-year-olds = 1 in 338
    • 40-year-olds = 1 in 84
    • 45-year-olds = 1 in 32

How are screenings for Down syndrome performed in pregnancy?

  • Chorionic villous sampling or amniocentesis are offered. The screening can include an ultrasound, maternal serum free beta-human chorionic gonadotropin (B-HCG) and pregnancy-associated plasma protein A. [7]

Invasive procedures carry risks (such as possible miscarriage), therefore, any woman considering an invasive procedure needs to thoroughly discuss the risks, benefits, and alternatives before undergoing any intervention.

Are patients with Down syndrome more likely to have health problems?

Yes, patients with patients with Down syndrome are predisposed to several health conditions to include:

  • delayed growth
  • specific facial features (flat face, large tongue);
  • problems with their immune system;
  • obstructive sleep apnea (75%);
  • heart defects(50%)[8];
  • mental learning disabilities (nearly 100%)[9];
  • decreased muscle tone; and
  • certain cancers.

What physical features are common in patients with Down syndrome?

Overall body size

Physically, children with Down syndrome tend to have a delay in normal growth.

Over time, a high percentage of children with Down syndrome will become overweight or obese.


It has been estimated that the combined prevalence of overweight and obesity in children with Down syndrome is between 23-70% based on a review of the literature.[10]

This is a younger boy who is obese and has Down syndrome. CamachoMD
This is a younger boy who is obese and has Down syndrome.

Mental abilities

It is estimated that practically all children with Down syndrome have mental learning disabilities, with an average intelligence quotient of 50, with a range from 30 to 70.[9]

Heart defects

Children with Down syndrome are also predisposed to having congenital heart defects, which is estimated to be present in up to 50% of Down syndrome neonates.[8]

The more common congenital heart defects in children with Down syndrome include:

  • atrioventricular septal defect (a hole between the 4 chambers of the heart, either the upper (atrial chambers) or lower chambers (ventricular chambers)),
  • patent ductus arteriosis (a connection between the heart and lungs that is supposed to close after birth, but does not close in children with a patent ductus arteriosis), and
  • tetralogy of fallot, which includes 4 problems: 1) enlarged aorta, 2) thicker than normal right ventricle, 3) ventricular septal defect, and 4) a completely or partially obstructed pulmonary valve.

Extremities

Concerning their hands, children with Down syndrome tend to have a curved or bent pinky (fifth finger) known as clinodactyly.

The foot and hand in a child with Down syndrome. Note there is a gap between the big toe and the second toe in the foot. The hand has a single crease going across the middle of the palm. CamachoMD
The foot and hand in a child with Down syndrome. Note there is a gap between the big toe and the second toe in the foot. The hand has a single crease going across the middle of the palm.

There is also a tendency for a single crease on their palms (single transverse palmar crease).

Concerning their feet, children with Down syndrome are predisposed to having a wide space or gap between the large toe (first toe) and the second toe.

Head, neck and facial features

Child with Down syndrome and physical features: A) wide gap between 1st and 2nd toes, B) curved 5th finger (clinodactyly) and a single crease on the palms, C) up-slanted eyes, epicanthic fold (skin fold that covers inner corner of eye), spots in the iris (Brushfield spots); and D) small and abnormally shaped ears. CamachoMD
Child with Down syndrome and physical features: A) wide gap between 1st and 2nd toes, B) curved 5th finger (clinodactyly) and a single crease on the palms, C) up-slanted eyes, epicanthic fold (skin fold that covers inner corner of eye), spots in the iris (Brushfield spots); and D) small and abnormally shaped ears.

Head, neck and facial features that are commonly observed in children with Down syndrome include[5]:

  • a flat head and flattened face;
  • up-slanted eyes (up-slanted palpebral fissures);
  • epicanthic fold (skin fold of the upper eyelid covers the inner corner of the eye);
  • spots in the iris (Brushfield spots);
  • a narrow palate;
  • abnormal teeth;
  • a large and protruding tongue;
  • abnormally shaped and small ears;
  • a short neck; and
  • nuchal skin folds (an increase in the amount of skin in the back part of the neck).
Adenoids enlarged and child in a child with Down Syndrome. Note the ear is lower set and her face has a flatter profile. Additionally, she is mouth breathing. CamachoMD
Adenoids enlarged and child in a child with Down Syndrome. Note the ear is lower set and her face has a flatter profile. Additionally, she is mouth breathing.

Children with Down syndrome are also predisposed to having recurring ear infections because of Eustachian tube dysfunction.

Health screenings that are common to children with Down syndrome:

Should all children with Down syndrome have a sleep study?

Research that summarized the published studies found that about 3 out of 4 children with Down syndrome have obstructive sleep apnea.[11]

Woman lying down. Her airway is blocked or obstructed by her soft palate, tongue and epiglottis. CamachoMD
Woman lying down. Her airway is blocked or obstructed by her soft palate, tongue and epiglottis.

Sleep apnea in Down syndrome is so common that The American Academy of Pediatrics that all children with Down syndrome have a sleep study to test for obstructive sleep apnea by age 4.[12]

But what if you think your child with Down syndrome does not have any breathing problems during sleep, should they still get a sleep study?

Yes, they should get a sleep study.

Research has shown that parents of children with Down syndrome are not able to accurately predict whether or not the child has obstructive sleep apnea based on their nighttime symptoms.[13]

Obstructive sleep apnea

Is there an increased risk of having obstructive sleep apnea in adult patients with Down syndrome?

Yes, approximately 35-42% of adults with Down syndrome have obstructive sleep apnea.[14]

Why do patients with Down syndrome have snoring and obstructive sleep apnea?

Obstructive sleep apnea and snoring are due to partial or complete upper airway obstruction during sleep.

Snoring is due to the vibration of the soft tissues of the upper airway, which in most circumstances is caused by the soft palate and the uvula.

Because of the flattened facial structures in patients with Down syndrome, the upper and lower jaw are not at the normal size and are positioned such that they narrow the airway size and that can make breathing more difficult.

The flattened facial features, smaller palate, and proportionally large tongue predispose patients with Down syndrome to having both snoring and obstructive sleep apnea.

Down Syndrome in a girl, showing extremely large adenoids. The adenoids are blocking her breathing, so she has to mouth breathe to get air. CamachoMD
Down Syndrome in a girl, showing extremely large adenoids. The adenoids are blocking her breathing, so she has to mouth breathe to get air.

For example, if a Down syndrome patient has a tongue is at the normal size, the tongue will be too large for the size of the upper airway because of the flattened facial structures.

What structures in the upper airway cause snoring and obstructive sleep apnea?

In general, the soft palate and the uvula are responsible for snoring.

Structures responsible for obstructive sleep apnea include the soft palate and uvula, the tonsils, the adenoids (if they are enlarged – especially in children), the tongue and structures of the larynx (epiglottis and supraglottis).

For patients who cannot tolerate CPAP therapy, and other medical management options have been tried and failed, surgery is a potential option.

What are the surgical options for treating obstructive sleep apnea in patients with Down syndrome?

In a large percentage of patients with obstructive sleep apnea, a tonsillectomy with adenoidectomy (if they are children, or if they are adults with large adenoids) will be the first-line option.

If you take all comers, a tonsillectomy with adenoidectomy is approximately 60 to 83% effective in children.[15, 16]

However, tonsillectomy with adenoidectomy is much less effective in overweight and obese children and even less effective in children with Down syndrome.

Tonsillectomy showing left side removed (the arrow points to the tonsil fossa). CamachoMD
Tonsillectomy showing left side removed (the arrow points to the wound bed or tonsillar fossa).

A study evaluating the research in the literature found that patients with Down syndrome that were treated with tonsillectomy and adenoidectomy had a drop in the apnea-hypopnea index decreased by only 51%.[17]

Despite, these numbers, over half (55%) of the surgeries performed for Down syndrome occur between 2-6 years of age.[18]  The most commonly performed surgery is tonsillectomy with adenoidectomy.[18]

Are patients with Down syndrome at an increased risk of atlantoaxial instability (neck instability) during head and neck surgeries such as tonsillectomies?

Yes, patients with Down syndrome are at an increased risk of having neck damage during tonsillectomies.

It is estimated that 10-30% of patients with Down syndrome have atlantoaxial instability.[19]

Surgeries in which the neck is extended, such as airway surgeries (adenoidectomy, tonsillectomy, tongue surgery, etc.) can increase the risk.

How common is craniocervical instability in patients with Down syndrome?

Craniocervical instability is estimated to occur in 8-63% of patients who have Down syndrome.[19]

What causes atlantoaxial instability in patients with Down syndrome?

The two main causes for atlantoaxial instability in Down syndrome include:

  • osseous abnormalities such as abnormal ossification of 1st cervical vertebrae and odontoideum; and
  • the occipital condyles are abnormally flattened.[20]

If a Down syndrome child is found to have atlantoaxial instability on an x-ray, does that mean they can’t have a tonsillectomy?

No, atlantoaxial instability in a Down syndrome patient doesn’t necessarily mean that the patient cannot have surgery, it just means that extra care needs to be taken during the surgery to make sure that the neck is kept in a neutral position and that it does not get extended.

The risks, benefits, and alternatives need to be discussed with your ENT surgeon.

After a tonsillectomy and adenoidectomy, is it common for a child with Down syndrome to have large tongue tonsils?

Yes, it is.

A study evaluating whether or not there are large tongue tonsils after a tonsillectomy and adenoidectomy found that they were markedly enlarged in 35% of patients with Down syndrome and only were markedly enlarged in 3% of children without Down syndrome.[21]

Patient selection is very important and may involve a pre-surgical sleep endoscopy to evaluate the extent of blockage that is due to the tongue.

Will reducing the size of the tongue help patients with Down syndrome?

Reducing the base of the tongue can help significantly in some patients with Down syndrome who have failed a tonsillectomy with adenoidectomy.

A common way to help estimate the amount of blockage that occurs at the back part of the tongue is to perform drug-induced sleep endoscopy.

Sleep endoscopy is when a patient is taken to the operating room to evaluate the upper airway during sleep, and the blockages are noted at the level of the soft palate, the tonsils if they are present, the back of the tongue, the larynx (epiglottis and the supraglottis).

Sleep endoscopy with partial obsruction at the base of tongue. The yellow arrows point to the blockage at the base of tongue in the child and also on the endoscope screen. BladeMD.com
Sleep endoscopy with partial obstruction at the base of tongue. The yellow arrows point to the blockage at the base of tongue in the child and also on the endoscope screen.

What is the medical management of obstructive sleep apnea in children and adults?

Medical management of obstructive sleep apnea in children and adults includes the trial of positive airway pressure (PAP or more commonly known as CPAP) therapy.

CPAP therapy can be challenging for patients with Down syndrome, as it is for most patients in general, and if the patient can adjust to it then it is a great option.

Down Syndrome in a boy, using CPAP. CamachoMD
Down Syndrome in a boy, using CPAP.

For patients who cannot tolerate CPAP therapy, and other medical management options have been tried and failed, surgery is a potential option.

Resources for Down syndrome:

National Down Syndrome Society

Global Down Syndrome Foundation

Band of Angels – the world’s largest provider of non-medical Down syndrome information

References:

1.            Rodman, R. and H.S. Pine, The otolaryngologist’s approach to the patient with Down syndrome. Otolaryngol Clin North Am, 2012. 45(3): p. 599-629, vii-viii.

2.            Kutzsche, S., John Langdon Down (1828-1896) – a pioneer in caring for mentally disabled patients. Acta Paediatr, 2018. 107(11): p. 1851-1854.

3.            Lamb, N.E., et al., Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nat Genet, 1996. 14(4): p. 400-5.

4.            Berend, S.A., et al., Molecular analysis of mosaicism for two different de novo acrocentric rearrangements demonstrates diversity in Robertsonian translocation formation. Am J Med Genet, 1998. 80(3): p. 252-9.

5.            Weijerman, M.E. and J.P. de Winter, Clinical practice. The care of children with Down syndrome. Eur J Pediatr, 2010. 169(12): p. 1445-52.

6.            Morris, J.K., D.E. Mutton, and E. Alberman, Revised estimates of the maternal age specific live birth prevalence of Down’s syndrome. J Med Screen, 2002. 9(1): p. 2-6.

7.            Nicolaides, K.H., et al., Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening. Ultrasound Obstet Gynecol, 2005. 25(3): p. 221-6.

8.            Kelly, A., et al., Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome. Pediatr Cardiol, 2018.

9.            Rachidi, M. and C. Lopes, Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways. Eur J Paediatr Neurol, 2008. 12(3): p. 168-82.

10.          Bertapelli, F., et al., Overweight and obesity in children and adolescents with Down syndrome-prevalence, determinants, consequences, and interventions: A literature review. Res Dev Disabil, 2016. 57: p. 181-92.

11.          Lee, C.F., et al., Prevalence of Obstructive Sleep Apnea in Children With Down Syndrome: A Meta-Analysis. J Clin Sleep Med, 2018. 14(5): p. 867-875.

12.          Bull, M.J., Health supervision for children with Down syndrome. Pediatrics, 2011. 128(2): p. 393-406.

13.          Friedman, N.R., et al., Accuracy of Parental Perception of Nighttime Breathing in Children with Down Syndrome. Otolaryngol Head Neck Surg, 2018. 158(2): p. 364-367.

14.          Hill, E.A., Obstructive sleep apnoea/hypopnoea syndrome in adults with Down syndrome. Breathe (Sheff), 2016. 12(4): p. e91-e96.

15.          Friedman, M., et al., Updated systematic review of tonsillectomy and adenoidectomy for treatment of pediatric obstructive sleep apnea/hypopnea syndrome. Otolaryngol Head Neck Surg, 2009. 140(6): p. 800-8.

16.          Brietzke, S.E. and D. Gallagher, The effectiveness of tonsillectomy and adenoidectomy in the treatment of pediatric obstructive sleep apnea/hypopnea syndrome: a meta-analysis. Otolaryngol Head Neck Surg, 2006. 134(6): p. 979-84.

17.          Nation, J. and M. Brigger, The Efficacy of Adenotonsillectomy for Obstructive Sleep Apnea in Children with Down Syndrome: A Systematic Review. Otolaryngol Head Neck Surg, 2017. 157(3): p. 401-408.

18.          Ong, A.A., et al., Down syndrome and pediatric obstructive sleep apnea surgery: A national cohort. Laryngoscope, 2018. 128(8): p. 1963-1969.

19.          Hankinson, T.C. and R.C. Anderson, Craniovertebral junction abnormalities in Down syndrome. Neurosurgery, 2010. 66(3 Suppl): p. 32-8.

20.          Margetis, K. and E.C. Benzel, Craniovertebral junction instability in adult patients with Down syndrome. World Neurosurg, 2015. 83(3): p. 334-6.

21.          Fricke, B.L., et al., Comparison of lingual tonsil size as depicted on MR imaging between children with obstructive sleep apnea despite previous tonsillectomy and adenoidectomy and normal controls. Pediatr Radiol, 2006. 36(6): p. 518-23.