Down Syndrome

Down Syndrome is a topic covered in the 5-Minute Clinical Consult.

To view the entire topic, please or .

5-Minute Clinical Consult (5MCC) app and website powered by Unbound Medicine helps you diagnose and manage 900+ medical conditions. Exclusive bonus features include Diagnosaurus DDx, 200 pediatrics topics, and medical news feeds. Explore these free sample topics:

-- The first section of this topic is shown below --

Basics

Description

  • Down syndrome (DS) is a congenital condition associated with intellectual disability and an increased risk of multisystem medical problems.
  • Systems affected: neurologic (100%), cardiac (40–50%), GI (8–12%)
  • Synonym: trisomy 21

Pediatric Considerations
Murmur may not be present at birth. Delay in recognition of heart condition may lead to irreversible pulmonary hypertension.

Geriatric Considerations

  • Life expectancy has increased to ~60 years.
  • Age-related health issues occur at earlier age than in the general population.
  • Communication difficulties may interfere with prompt recognition of some medical issues.

Pregnancy Considerations

  • American College of Obstetricians and Gynecologists (ACOG) recommends all pregnant women be offered traditional prenatal screening and diagnostic testing for DS.
    • Maternal prenatal screening may be performed in the 1st or 2nd trimester.
    • Prenatal diagnostic tests include chorionic villus sampling or amniocentesis.
  • ACOG and the Society for Maternal-Fetal Medicine (SMFM) acknowledge that any women may choose noninvasive prenatal screening (NIPS). American College of Medical Genetics and Genomics (ACMG) recommends all women be offered NIPS (1,2).
  • Most, but not all, men with DS are believed to be infertile.
  • Most women with DS are subfertile but can conceive children with and without DS.

Epidemiology

Incidence
In the United States, 1/792 live births, ~5,300 births per year (3)

Prevalence
~206,000 persons in the United States (4)

Etiology and Pathophysiology

  • Etiology: presence of all or part of an extra chromosome 21
  • Trisomy 21: 95% of DS, an extra chromosome 21 is found in all cells due to nondisjunction, usually in maternal meiosis.
  • Translocation DS: 3–4% of DS, extra chromosome 21q material is translocated to another chromosome (usually 13, 14, or 21); ~25% have parental origin.
  • Mosaic trisomy 21: 1–2% of DS, manifestations may be milder.

Genetics
  • Online Mendelian Inheritance in Man (OMIM) 190685
  • Inheritance: most commonly sporadic nondisjunction resulting in trisomy 21
  • Chance of having another child with DS is
    • 1% (or age risk, whichever is greater) after conceiving a pregnancy with nondisjunction trisomy 21
    • 10–15% for mothers/sisters and 3–5% for fathers/brothers who carry balanced translocation with chromosome 21
    • 100% if the parental balanced translocation is 21;21 (45,t[21;21])
    • Unclear after child with mosaic DS but ~1%

Risk Factors

  • DS believed to occur in all races and ethnicities with equal frequency
  • Chance of having an infant with DS increases with mother’s age
  • Relatively more infants with DS are born to younger mothers because younger women are more likely to become pregnant.
  • Prenatal diagnosis of DS is more common in older women, and a high percentage of such pregnancies are electively terminated.

General Prevention

  • No prevention for nondisjunction trisomy 21
  • Preimplantation diagnosis with in vitro fertilization (IVF), prenatal diagnosis followed by termination, and adoption are current options for expectant parents who do not wish to raise a child with DS.

Commonly Associated Conditions

  • Cardiac
    • Congenital heart defects (40–50%)
  • GI/growth
    • Feeding problems are common in infancy.
    • Structural defects (~12%)
    • Gastroesophageal reflux
    • Constipation
    • Celiac disease (~5%)
  • Pulmonary
    • Tracheal stenosis/tracheoesophageal fistula
    • Pulmonary hypertension
    • Obstructive sleep apnea (50–75%)
  • Genitourinary
    • Cryptorchidism, hypospadias
  • Hematologic/neoplastic
    • Transient myeloproliferative disorder (~10%): generally resolves spontaneously; can be preleukemic (acute megakaryoblastic leukemia [AMKL]) in 20–30%
    • Leukemia (AMKL or acute lymphoblastic leukemia [ALL]) in 0.5–1%
    • Decreased risk of most solid tumors; increased risk of germ cell tumors/testicular cancer
  • Endocrine
    • Hypothyroidism: congenital or acquired (13–63%)
    • Diabetes
  • Skeletal
    • Atlantoaxial instability (15%): ~2% symptomatic
    • Short stature is common.
    • Scoliosis (some cases have adult onset)
    • Hip problems (1–4%)
  • Immune/rheumatologic
    • Abnormal immune function with increased rate of respiratory infections
    • Increased risk of autoimmune disorders, including Hashimoto thyroiditis, celiac disease, and alopecia
  • Neurologic
    • Intellectual ability ranging from mild to severe disability. Average is moderate intellectual disability.
    • Autism spectrum disorder (<18%)
    • Seizures (8%); typically occurring <1 year of age (infantile spasms) or >30 years of age
    • Alzheimer disease: At least 40% at age 40 years develop signs of dementia; percentage increases with age.
  • Psychiatric
    • Attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and autism spectrum disorder increased frequency in children.
    • Generalized depression and anxiety with increased frequency in young adults/adults
  • Sensory
    • Hearing loss (75%): mostly conductive due to high frequency of asymptomatic middle ear effusion; otitis media (50–70%)
    • Visual impairment (60%): strabismus (refractive errors, 15%), myopia, hyperopia, nystagmus, cataracts (15%)
  • Dermatologic
    • Xerosis, eczema, palmoplantar hyperkeratosis, atopic or seborrheic dermatitis, onychomycosis, syringomas, furunculosis/folliculitis, hidradenitis suppurativa

-- To view the remaining sections of this topic, please or --

Basics

Description

  • Down syndrome (DS) is a congenital condition associated with intellectual disability and an increased risk of multisystem medical problems.
  • Systems affected: neurologic (100%), cardiac (40–50%), GI (8–12%)
  • Synonym: trisomy 21

Pediatric Considerations
Murmur may not be present at birth. Delay in recognition of heart condition may lead to irreversible pulmonary hypertension.

Geriatric Considerations

  • Life expectancy has increased to ~60 years.
  • Age-related health issues occur at earlier age than in the general population.
  • Communication difficulties may interfere with prompt recognition of some medical issues.

Pregnancy Considerations

  • American College of Obstetricians and Gynecologists (ACOG) recommends all pregnant women be offered traditional prenatal screening and diagnostic testing for DS.
    • Maternal prenatal screening may be performed in the 1st or 2nd trimester.
    • Prenatal diagnostic tests include chorionic villus sampling or amniocentesis.
  • ACOG and the Society for Maternal-Fetal Medicine (SMFM) acknowledge that any women may choose noninvasive prenatal screening (NIPS). American College of Medical Genetics and Genomics (ACMG) recommends all women be offered NIPS (1,2).
  • Most, but not all, men with DS are believed to be infertile.
  • Most women with DS are subfertile but can conceive children with and without DS.

Epidemiology

Incidence
In the United States, 1/792 live births, ~5,300 births per year (3)

Prevalence
~206,000 persons in the United States (4)

Etiology and Pathophysiology

  • Etiology: presence of all or part of an extra chromosome 21
  • Trisomy 21: 95% of DS, an extra chromosome 21 is found in all cells due to nondisjunction, usually in maternal meiosis.
  • Translocation DS: 3–4% of DS, extra chromosome 21q material is translocated to another chromosome (usually 13, 14, or 21); ~25% have parental origin.
  • Mosaic trisomy 21: 1–2% of DS, manifestations may be milder.

Genetics
  • Online Mendelian Inheritance in Man (OMIM) 190685
  • Inheritance: most commonly sporadic nondisjunction resulting in trisomy 21
  • Chance of having another child with DS is
    • 1% (or age risk, whichever is greater) after conceiving a pregnancy with nondisjunction trisomy 21
    • 10–15% for mothers/sisters and 3–5% for fathers/brothers who carry balanced translocation with chromosome 21
    • 100% if the parental balanced translocation is 21;21 (45,t[21;21])
    • Unclear after child with mosaic DS but ~1%

Risk Factors

  • DS believed to occur in all races and ethnicities with equal frequency
  • Chance of having an infant with DS increases with mother’s age
  • Relatively more infants with DS are born to younger mothers because younger women are more likely to become pregnant.
  • Prenatal diagnosis of DS is more common in older women, and a high percentage of such pregnancies are electively terminated.

General Prevention

  • No prevention for nondisjunction trisomy 21
  • Preimplantation diagnosis with in vitro fertilization (IVF), prenatal diagnosis followed by termination, and adoption are current options for expectant parents who do not wish to raise a child with DS.

Commonly Associated Conditions

  • Cardiac
    • Congenital heart defects (40–50%)
  • GI/growth
    • Feeding problems are common in infancy.
    • Structural defects (~12%)
    • Gastroesophageal reflux
    • Constipation
    • Celiac disease (~5%)
  • Pulmonary
    • Tracheal stenosis/tracheoesophageal fistula
    • Pulmonary hypertension
    • Obstructive sleep apnea (50–75%)
  • Genitourinary
    • Cryptorchidism, hypospadias
  • Hematologic/neoplastic
    • Transient myeloproliferative disorder (~10%): generally resolves spontaneously; can be preleukemic (acute megakaryoblastic leukemia [AMKL]) in 20–30%
    • Leukemia (AMKL or acute lymphoblastic leukemia [ALL]) in 0.5–1%
    • Decreased risk of most solid tumors; increased risk of germ cell tumors/testicular cancer
  • Endocrine
    • Hypothyroidism: congenital or acquired (13–63%)
    • Diabetes
  • Skeletal
    • Atlantoaxial instability (15%): ~2% symptomatic
    • Short stature is common.
    • Scoliosis (some cases have adult onset)
    • Hip problems (1–4%)
  • Immune/rheumatologic
    • Abnormal immune function with increased rate of respiratory infections
    • Increased risk of autoimmune disorders, including Hashimoto thyroiditis, celiac disease, and alopecia
  • Neurologic
    • Intellectual ability ranging from mild to severe disability. Average is moderate intellectual disability.
    • Autism spectrum disorder (<18%)
    • Seizures (8%); typically occurring <1 year of age (infantile spasms) or >30 years of age
    • Alzheimer disease: At least 40% at age 40 years develop signs of dementia; percentage increases with age.
  • Psychiatric
    • Attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and autism spectrum disorder increased frequency in children.
    • Generalized depression and anxiety with increased frequency in young adults/adults
  • Sensory
    • Hearing loss (75%): mostly conductive due to high frequency of asymptomatic middle ear effusion; otitis media (50–70%)
    • Visual impairment (60%): strabismus (refractive errors, 15%), myopia, hyperopia, nystagmus, cataracts (15%)
  • Dermatologic
    • Xerosis, eczema, palmoplantar hyperkeratosis, atopic or seborrheic dermatitis, onychomycosis, syringomas, furunculosis/folliculitis, hidradenitis suppurativa

There's more to see -- the rest of this entry is available only to subscribers.