Down Syndrome – Resources For Clinicians and Parents

What follows is my review of Down Syndrome.

The best place to start in reviewing Down Syndrome for both clinicians and parents is lecture, The Neurodevelopment of and Behavioral Complexity of Trisomy 21 [Down Syndrome] from The Children’s Hospital Of Philadelphia (CHOP) June 5, 2018. It is an outstanding review and update of Down Syndrome.

Next, review the 2011 guideline Health Supervision for Children With Down Syndrome from AAP. Here are some excerpts from the article [But read the whole article as it helps to reinforce the lecture above]:

And next I reviewed Down Syndrome Updated: Apr 30, 2018 from emedicine.medscape.com. The article gave continued reinforcement.

Here are some excerpts from the article:

Current evidence does not support performing routine screening radiographs for the assessment of potential atlantoaxial instability in asymptomatic children. However, imaging studies that may be considered include the following:

  • Echocardiography in every newborn suspected of having trisomy 21 to identify congenital heart disease, since approximately 50% of those with Down syndrome will have congenital heart disease

  • Ultrasonography

Postnatal diagnostic tests that may be warranted include the following:

  • Auditory brainstem response (ABR), or brainstem auditory evoked response (BAER)

  • Pediatric ophthalmic examination

See Workup for more detail.

Background

Down syndrome is by far the most common and best known chromosomal disorder in humans and the most common cause of intellectual disability. [34567It is characterized by intellectual disability, dysmorphic facial features, and other distinctive phenotypic traits. Down syndrome is primarily caused by trisomy of chromosome 21; this is the most common trisomy among live births. The term mongolism was once commonly used for Down syndrome but is now considered obsolete. [8910]

Like most diseases associated with chromosomal abnormalities, trisomy 21 gives rise to multiple systemic complications as part of the clinical syndrome. This chromosomal anomaly leads to both structural and functional defects in patients with Down syndrome. However, not all defects occur in each patient; there is a wide range of phenotypic variation. [1]

Etiology

Down syndrome is caused by the following 3 cytogenic variants:

  • Three full copies of chromosome 21
  • Chromosomal translocation that results in 3 copies of the critical region for Down syndrome
  • Mosaicism

In 94% of patients with Down syndrome, full trisomy 21 is the cause; mosaicism (2.4%) and translocations (3.3%) account for the remaining cases. Approximately 75% of the unbalanced translocations are de novo, and approximately 25% result from familial translocation.

A free trisomy 21 results from nondisjunction during meiosis in one of the parents. This occurrence is correlated with advanced maternal and paternal age. About 95% of the time, the error is maternal nondisjunction, with meiosis I errors occurring three times as frequently as meiosis II errors. The remaining 5% cases are paternal in origin, and meiosis II errors predominate.

Advanced maternal age remains the only well-documented risk factor for maternal meiotic nondisjunction. However, understanding of the basic mechanism behind the maternal age effect is lacking.

Epidemiology

Down syndrome is the most common autosomal abnormality. The frequency is about 1 case in 800 live births. Each year, approximately 6000 children are born with Down syndrome. [15Down syndrome accounts for about one third of all moderate and severe mental handicaps in school-aged children. The prevalence of Down syndrome worldwide has increased because of increases in life span in the last few decades.

Occurrence is strongly dependent on maternal age. The incidence of this syndrome at various maternal ages is as follows:

  • 15-29 years – 1 case in 1500 live births
  • 30-34 years – 1 case in 800 live births
  • 35-39 years – 1 case in 270 live births
  • 40-44 years – 1 case in 100 live births
  • Older than 45 years – 1 case in 50 live births

Prognosis

The overall outlook for individuals with Down syndrome has dramatically improved. Many adult patients are healthier and better integrated into society, and life expectancy has improved from 25 years in 1983 to 60 years or higher today.

Approximately 75% of concepti with trisomy 21 die in embryonic or fetal life. Approximately 25-30% of patients with Down syndrome die during the first year of life. The most frequent causes of death are respiratory infections (bronchopneumonia) and congenital heart disease. The median age at death is in the mid-50s.

Congenital heart disease is the major cause of morbidity and early mortality in patients with Down syndrome. In addition, esophageal atresia with or without transesophageal (TE) fistulaHirschsprung diseaseduodenal atresia, and leukemia contribute to mortality. The high mortality later in life may be the result of premature aging.

History

When recording the history from the parents of a child with Down syndrome, the clinician should include the following [19:

  • Parental concern about hearing, vision, developmental delay, respiratory infections, and other problems

  • Feeding history to ensure adequate caloric intake

  • Prenatal diagnosis of Down syndrome

  • Vomiting secondary to GI tract blockage by duodenal web or atresia

  • Absence of stools secondary to Hirschsprung disease

  • Delay in cognitive abilities, motor development, language development (specifically expressive skills), and social competence

  • Arrhythmia, fainting episodes, palpitations, or chest pain secondary to heart lesion

  • Symptoms of sleep apnea, including snoring, restlessness during sleep, difficulty awaking, daytime somnolence, behavioral changes, and school problems

  • A history of possible physical or sexual abuse

Symptoms of atlantoaxial instability include the following:

  • About 13-14% of patients have radiographic evidence of atlantoaxial instability but no symptoms

  • Only 1-2% of patients have symptoms that require treatment

  • Symptoms include easy fatigability, neck pain, limited neck mobility or head tilt, torticollis, difficulty walking, change in gait pattern, loss of motor skills, incoordination, clumsiness, sensory deficits, spasticity, hyperreflexia, clonus, extensor-plantar reflex, loss of upper-body strength, abnormal neurologic reflexes, change in bowel and bladder function, increased muscle tone in the legs, and changes in sensation in the hands and feet

  • These symptoms often remain relatively stable for months or years

  • In rare cases, the symptoms progress to paraplegia, hemiplegia, quadriplegia, or death

Physical Examination [Link is to all of the findings

Radiography and Ultrasonography

Current evidence does not support performing routine screening radiographs for assessment of potential atlantoaxial instability in asymptomatic children. When obtained, skull series show evidence of flattened facial features (including small or absent nasal bones), hypoplastic sinuses, a flat occiput, microcephaly, and brachycephaly.

Cervical radiography (with lateral flexion and extension views) is required to measure the atlantodens distance and to rule out atlantoaxial instability at the age of 3 years. Radiography is also used before administering anesthesia if signs suggest spinal cord compression. Magnetic resonance imaging (MRI) is also recommended regularly for evaluation.

Reduced iliac and acetabular angles may be present in young infants. Short hands with shortened digits and clinodactyly due to hypoplastic middle phalanx of the fifth finger may be present.

Echocardiography should be performed on all infants suspected of having trisomy 21 to identify congenital heart disease, regardless of findings on physical examination.

Cell-free fetal DNA screening

Cell-free fetal DNA is composed of fragments of fetal DNA derived from the placenta that can be found in maternal plasma. The fragments can be seen in maternal circulation as early as 7 weeks’ gestation and last throughout pregnancy, becoming undetectable in the maternal circulation a few hours after birth. The cell-free fetal DNA screening test can be done at any gestational age after 10 weeks and can detect about 99% of Down syndrome pregnancies. Adoption of cell-free DNA for screening women has been slow because of cost, but it is currently used at many centers for screening women at high risk for offspring with Down syndrome. Studies have shown that this test has a high sensitivity and specificity. [89909192,939495]

Next review Atlantoaxial Instability in Down Syndrome from emedicine.medscape.ccom

And finally, review Down Syndrome Airway from Dr. Fox’s outstanding Pediatric EM Morsels.

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