Aneuploidy of Autosomes
Aneuploidy denotes an abnormal number of chromosomes in cells. The presence of 3 homologous chromosomes in a cell, rather than the normal pair, is termed trisomy. Monosomy is the presence of only 1 member of any pair of autosomes or only 1 sex chromosome. The absence of a single autosome is almost always lethal to the embryo; an extra autosome is often catastrophic to surviving embryos. Aneuploidy of sex chromosomes (eg, X, XXX, XXY, and XYY) is less disastrous. Monosomies and trisomies are generally caused by mechanical accidents that increase or decrease the number of chromosomes in the gametes. The most common type of accident, meiotic nondisjunction, results from a disruption of chromosome movement during meiosis (see Fig 6-5).
Trisomy 21 syndrome, or Down syndrome, is the most common chromosomal syndrome in humans; it has an overall incidence of 1:800 live births. Clinical features of this syndrome have been well known since John Langdon Down originally described them in 1866.
The most important risk factor for having a child with Down syndrome is maternal age. The frequency of Down syndrome increases from approximately 1:1400 live births for mothers aged 20–24 years to approximately 1:40 live births for mothers aged 44 years. However, the frequency of Down syndrome is greater (1:1250) for mothers between 15 and 19 years of age than it is in the next-higher age range. Above age 50 years, the frequency is 1:11 live births. The eponym Down syndrome summarizes a clinical description of certain distinctive, if variable, phenotypic features whereas the karyotype describes the chromosomal constitution of the cells and tissues studied.
In more than 80% of Down syndrome cases, the genetic error occurs in meiosis I (see Chapter 5); and in more than 95% of cases, the error occurs in maternal rather than paternal meiosis. Approximately 5% of patients with Down syndrome have a translocation resulting from attachment of the long arm of chromosome 21 to the long arm of another acrocentric chromosome, usually 14 or 22. These translocations cause pairing problems during meiosis, and the translocated fragment of chromosome 21 appears in one of the daughter cells along with a normal chromosome 21. As in nondisjunction, the fragment becomes trisomic on fertilization. Trisomy of only the distal one-third of chromosome arm 21q is sufficient to cause the disorder. Genes that lie within the q22 band of chromosome 21 appear to be specifically responsible for the pathogenesis of Down syndrome.
Patients with Down syndrome may exhibit the following features:
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cognitive disabilities
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characteristic facies: oblique palpebral fissure, epicanthus, flat nasal bridge, and protruding tongue
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short, broad hands and wide space between first and second toes; characteristic dermatoglyphics
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hypotonia
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congenital heart disease
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immunologic, hematologic anomalies
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gastrointestinal anomalies
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atlantoaxial instability
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epilepsy
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Alzheimer disease
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short stature
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infertility
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dental hypoplasia
Table 6-6 Ocular Findings in Down Syndrome (Trisomy 21)
Ophthalmic features of Down syndrome are presented in Table 6-6.
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Leonard S, Bower C, Petterson B, Leonard H. Medical aspects of school-aged children with Down syndrome. Dev Med Child Neurol. 1999;41(10):683–688.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.