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Disease Profile

Down syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Trisomy 21; Down's syndrome

Summary

Down syndrome is a chromosome disorder associated with intellectual disability, a characteristic facial appearance, with small nose and an upward slant to the eyes, and low muscle tone in infancy.[1][2] The degree of intellectual disability varies from mild to moderate. People with Down syndrome may also be born with various health concerns such as heart defects or digestive abnormalities, as well as short stature and a single deep crease across the center of the palm. They also have an increased risk to develop gastroesophageal reflux, celiac disease, hypothyroidism, hearing and vision problems, leukemia, and Alzheimer disease. Down syndrome is caused by having three copies of chromosome 21 (called trisomy 21) instead of the usual two copies and is typically not inherited.[2][3][4] Treatment focuses on the specific symptoms in each person. There is ongoing research about the specific genes causing the disease aiming to find more effective treatments.[4] 

Symptoms

People with Down syndrome may develop the following medical problems:[2] 

  • Congenital hypothyroidism
  • Hearing loss
  • Congenital heart defects
  • Seizures
  • Vision disorders
  • Decreased muscle tone (hypotonia)

Children with Down syndrome are also more likely to develop chronic respiratory infections, middle ear infections, and recurrent tonsillitis. In addition, there is a higher incidence of pneumonia in children with Down syndrome than in the general population.[2]

Children with Down syndrome have developmental delay. They are often slow to turn over, sit, and stand. Developmental delay may be related to the child's weak muscle tone. Development of speech and language may also take longer than expected. Children with Down syndrome may take longer than other children to reach their developmental milestones, but many of these milestones will eventually be met.[2]

Adults with Down syndrome have an increased risk of developing Alzheimer disease, a brain disorder that results in a gradual loss of memory, judgment, and ability to function. Although Alzheimer disease is usually a disorder that occurs in older adults, about half of adults with Down syndrome develop this condition by age 50.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Brachycephaly
Short and broad skull
0000248
Brachydactyly
Short fingers or toes
0001156
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Flat face
Flat facial shape
0012368
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Muscular hypotonia
Low or weak muscle tone
0001252
Round ear
0100830
Short neck
Decreased length of neck
0000470
Thickened nuchal skin fold
Thickened skin folds of neck
Thickened skin over the neck

[ more ]

0000474
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
30%-79% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Abnormality of immune system physiology
0010978
Abnormality of the fontanelles or cranial sutures
0000235
Abnormality of the lymphatic system
0100763
Bilateral single transverse palmar creases
0007598
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Decreased fertility
Abnormal fertility
0000144
Depressed nasal ridge
Flat nose
Recessed nasal ridge

[ more ]

0000457
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Microdontia
Decreased width of tooth
0000691
Narrow mouth
Small mouth
0000160
Narrow palate
Narrow roof of mouth
0000189
Obesity
Having too much body fat
0001513
Open mouth
Gaped jawed appearance
Gaped mouthed appearance
Slack jawed appearance

[ more ]

0000194
Prematurely aged appearance
Precociously senile appearance
0007495
Protruding tongue
Prominent tongue
Tongue sticking out of mouth

[ more ]

0010808
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe

[ more ]

0001852
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip

[ more ]

0000179
Umbilical hernia
0001537
5%-29% of people have these symptoms
Acute megakaryocytic leukemia
0006733
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Anal atresia
Absent anus
0002023
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Hypothyroidism
Underactive thyroid
0000821
Impaired pain sensation
Decreased pain sensation
0007328
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Renal hypoplasia/aplasia
Absent/small kidney
Absent/underdeveloped kidney

[ more ]

0008678
Sparse hair
0008070
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Type II diabetes mellitus
Noninsulin-dependent diabetes
Type 2 diabetes
Type II diabetes

[ more ]

0005978
Percent of people who have these symptoms is not available through HPO
Alzheimer disease
Late-onset form of familial Alzheimer disease
0002511
Atlantoaxial instability
0003467
Broad palm

Cause

There are 3 possible genetic causes of Down syndrome:[2][3][5]

  • Trisomy 21. Most often, Down syndrome is caused by an extra chromosome 21 in all cells of the affected person. In these cases, the chromosome 21 pair fails to separate during the formation of an egg (or sperm); this is called "nondisjunction." When the egg with 2 copies of chromosome 21 unites with a normal sperm with one copy of chromosome 21 to form an embryo, the resulting embryo has 3 copies of chromosome 21 instead of the normal two.The extra chromosome is then copied in every cell of the baby's body, causing the features of Down syndrome.

    The cause of nondisjunction is unknown, but research has shown that it happens more often as women age. Nondisjunction is not known to be caused by anything in the environment or anything that parents do (or don't do) before or during pregnancy.

  • Mosaic trisomy 21. In about 1-2% of cases, only some of the cells in a person's body have an extra chromosome 21; this is called "mosaic trisomy 21". In this situation, the fertilized egg may have the right number of chromosomes, but due to a cell division error early in the development of the embryo, some cells "acquire" an extra chromosome 21. A person with mosaic trisomy 21 typically has 46 chromosomes in some cells, and 47 chromosomes (with the extra chromosome 21) in others. The features and severity in people with mosaic trisomy 21 may vary widely.
  • Translocation trisomy 21. About 3-4% of people with Down syndrome have cells that contain 46 chromosomes; however, there is extra chromosome 21 material attached (translocated) onto another chromosome. For parents of a child with Down syndrome due to a translocation, there may be an increased chance of Down syndrome in future pregnancies. This is because one of the two parents may be a carrier of a balanced translocation. However, not all parents of people with translocation trisomy 21 have a translocation.
Regardless of the type of Down syndrome a person has, all people with Down syndrome have an extra, critical portion of chromosome 21 present in all or some of their cells. This extra genetic material disrupts the normal course of development, causing the characteristic features of Down syndrome.[2][6]

Diagnosis

Down syndrome may be suspected and/or diagnosed during pregnancy, or after a child is born.

During pregnancy, a woman can opt to have specific tests that may either screen for, or diagnosis, Down syndrome in a fetus. A screening test poses no risks to the fetus and can determine the likelihood that a fetus has Down syndrome. It may show that a fetus is at an increased risk to be affected, but cannot determine whether it is definitely affected. Screening tests for Down syndrome may involve different types of blood tests for the mother and/or specific types of ultrasounds that can detect features more common in fetuses with Down syndrome (called markers). Depending on the type of screening tests a woman has, they may be done during the 1st trimester, the 2nd trimester, or both. If a screening test shows an increased risk for Down syndrome, a woman may then choose to have a diagnostic test.[7]

Diagnostic tests during pregnancy can determine with certainty whether a fetus has Down syndrome, but they are invasive and carry a slight risk of miscarriage. Examples of diagnostic tests include chorionic villus sampling in the 1st trimester and amniocentesis in the 2nd trimester. During these tests, a small sample of genetic material is obtained from the amniotic fluid or placenta, and the fetus' chromosomes are then analyzed in a laboratory.[7]

In recent years, non-invasive prenatal testing (NIPT) has become available to women who are at increased risk to have a baby with Down syndrome. NIPT is a blood test that examines DNA from the fetus in the mother's bloodstream. However, women who have a positive NIPT result should then have invasive diagnostic testing to confirm the result.

People with questions about the different options for prenatal screening or diagnostic testing should speak with a genetic counselor. A genetic counselor can discuss the benefits, limitations and risks of each test, and help each person decide which test (if any) is best for them.

If a diagnosis of Down syndrome is not made prenatally, the diagnosis can be made in the newborn. Down syndrome may be suspected if a newborn has characteristic physical features of the condition. The diagnosis can then be confirmed by obtaining a karyotype (a blood test to look at a picture of the newborn's chromosomes).[8]

Treatment

Early intervention services, quality educational programs, a stimulating home environment, good health care, and positive support from family and friends can help people with Down syndrome develop to their full potential.[6] The overall goal of treatment is to boost cognition by improving learning, memory, and speech.[9] Other treatments depend on the specific health problems or complications present in each affected person. The Research Down syndrome Foundation have a webpage with information about active reseach projects.

Management Guidelines

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides information related to the health of children, adults, and families. Click on the link to view information on this topic.
      • March of Dimes has a factsheet on Down syndrome.
      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Down syndrome. This website is maintained by the National Library of Medicine.
      • The Merck Manual provides information on this condition for patients and caregivers.
      • The National Dissemination Center for Children with Disabilities provides information on Down syndrome.
      • A Positive Exposure program called FRAME has an educational film about Down syndrome that was created to change how medical information is presented to healthcare professionals. FRAME stands for Faces Redefining the Art of Medical Education. Positive Exposure is an organization that uses photography, film, and narrative to transform public perceptions of people living with genetic, physical, intellectual, and behavioral differences.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Down syndrome. Click on the link to view a sample search on this topic.

          References

          1. Down syndrome. Online Mendelian Inheritance In Man (OMIM). 2017; https://www.ncbi.nlm.nih.gov/omim/190685.
          2. Down syndrome. Genetics Home Reference Web site. June, 2012; https://ghr.nlm.nih.gov/condition=downsyndrome.
          3. Chen H. Down Syndrome. Medscape Reference. 2017; https://emedicine.medscape.com/article/943216-overview.
          4. Down Syndrome. March of Dimes. 2009; https://www.marchofdimes.com/baby/birthdefects_downsyndrome.html.
          5. Down Syndrome. Genetic Science Learning Center. 2015; https://learn.genetics.utah.edu/content/disorders/chromosomal/down/. Accessed 7/28/2015.
          6. What Is Down Syndrome?. National Down Syndrome Society. 2012; https://www.ndss.org/Down-Syndrome/What-Is-Down-Syndrome/. Accessed 7/28/2015.
          7. How do health care providers diagnose Down syndrome?. NICHHD. January 17, 2014; https://www.nichd.nih.gov/health/topics/down/conditioninfo/pages/diagnosed.aspx.
          8. Nina N. Powell-Hamilton. Down Syndrome. Merck Manuals. December 2012; https://www.merckmanuals.com/professional/pediatrics/chromosomal-anomalies/down-syndrome.
          9. DS 101. Down Syndrome Research and Treatment Foundation. 2015; https://www.dsrtf.org/page.aspx?pid=352. Accessed 7/28/2015.

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