Down Syndrome
To view the entire topic, please log in or purchase a subscription.
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 log in or purchase a subscription --
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.