Excerpt from Down Syndrome

Please click here to view the full topic text: Down Syndrome

Background

Down syndrome is a frequent form of mental retardation associated with characteristic morphologic features (mongolism) and many somatic abnormalities due to a number of chromosomal aberrations.

The characteristic clinical features that discriminate the syndrome from other mental deficiencies were first described by John Langdon Down¹ in 1866. The condition has typical physical features and multisystem anomalies, some of which are dermatologic. The skin lesions in this syndrome were noted by Seguin (1846), who spoke of d'idiots furfuraces. Certain dermatoglyphic features in Down syndrome that differed from control subjects were pointed out in 1939. In 1959, a chromosomal abnormality was proven to cause Down syndrome.²

Other eMedicine articles on Down syndrome are as follows:

• Down Syndrome (ophthalmology
• Down Syndrome (pediatrics)
• Down Syndrome, Postnatal Findings (radiology)
• Down Syndrome, Prenatal Findings (radiology)

Additionally, the Medscape CME course Antioxidant, Folinic Acid Supplements May Not Be Helpful in Down's Syndrome may be of interest.

Pathophysiology

Three cytogenetic variants cause Down syndrome: trisomy 21, chromosomal translocation, and mosaicism.

Trisomy 21 accounts for nearly 95% of all patients with Down syndrome. Most of the remaining patients have 46 chromosomes with translation of the long arm of an extra number 21 either to a D group or to another G group chromosome. As a woman ages, her risk of giving birth to a child with Down syndrome increases. This is of particular concern for women older than 35 years.

Less commonly, patients with Down syndrome may have 46 chromosomes with either 21/22 translocation or 21/21 translocation.

A few patients have mosaicism with a normal cell line, usually milder physical stigmata, and impaired intelligence.

Two different hypotheses have been proposed to explain the mechanism of gene action in Down syndrome: developmental instability (loss of chromosomal balance) and "gene dosage effect".³ According to the gene dosage effect hypothesis, the genes located on chromosome 21 have been overexpressed in cells and tissues of Down syndrome patients, and this contributes to the phenotypic abnormalities.⁴

Frequency

United States

The frequency is 1 case in 800 live births or approximately 6000 children per year.

International

Down syndrome is the most common autosomal abnormality and occurs in approximately 1 case per 700 live births. Down syndrome accounts for about one third of all moderate and severe mental handicaps in school-aged children.

Mortality/Morbidity

• 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 life expectancy of patients with Down syndrome is slightly reduced.

Race

Down syndrome has been reported in people of all races.

Sex

Both sexes are affected equally. The sexual incidence of patients with Down syndrome is the same. Males with Down syndrome are sterile. In the few affected females who have had children, about one half of the offspring have been affected.

Age

Characteristic morphologic features of mongolism can be recognized immediately at birth, but they are obvious in children older than 1 year. Some dermatologic features increase with advancing age.

Please click here to view the full topic text: Down Syndrome