Anesthetic considerations in the patient with down syndrome

Published on 07/02/2015 by admin

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Last modified 07/02/2015

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Anesthetic considerations in the patient with down syndrome

Michael J. Murray, MD, PhD and Jennifer A. Rabbitts, MB, ChB

Trisomy 21 (three copies of chromosome 21) accounts for 95% of the cases of Down syndrome (DS), the most common chromosomal abnormality (1:691 live births, according to the Centers for Disease Prevention and Control) and also the most common genetic cause of intellectual disability. The other 5% of patients have DS due to mosaicism (two populations of cells in the same individual, some with two copies of chromosome 21, the rest with three copies of chromosome 21) or due to translocation of part of chromosome 21 onto another chromosome such that there are triplicate copies of a sufficient number of genes to produce the syndrome.

How trisomy 21 causes the multiple genetic deficits associated with DS is not known, but progress is being made. Chromosome 21 is the smallest of the human chromosomes, but it is a very small part of the chromosome that is most likely involved in the genesis of DS. Because of areas of synteny (the correspondence of genes located on the same chromosome in several species) between the human and mouse genomes, researchers have been able to use mouse models to pinpoint the specific genes on human chromosome 21 that are most likely involved in producing symptoms of DS. The Ts65Dn mouse, which carries 132 genes that are syntenic with human chromosome 21, has facial characteristics, memory and learning problems, and age-related changes in the forebrain similar to what is seen in human DS. Studies in other animal models suggest that more than 400 genes are triplicated in DS. Scientists are of the opinion that the deficits seen in DS are not due to a single triplicate copy of one gene but, rather, to several genes or the interaction of several genes. Most recently, investigators have developed a pluripotent stem cell line that contains triplicate copies of genes of interest; the investigators have been able to transform some of these cells into neurons that display reduced synaptic activity, affecting excitatory and inhibitory synapses equally, deficits that are consistent with the cognitive deficits seen in individuals with DS.

The most significant risk factor for trisomy 21—maternal age—was thought more than a century ago to be due to “uterine exhaustion.” However, we now know that older mothers have more babies with DS because the frequency of meiotic nondisjunction increases with increasing maternal age. The American College of Obstetricians and Gynecologists recommends that all pregnant women undergo nuchal translucency ultrasound, amniocentesis, or chorionic villus sampling during the first few months of pregnancy to check for DS.

Clinical manifestations

Abnormalities associated with DS, including abnormalities of the nasal structures and decreased blood flow into the right atrium, are apparent in utero via ultrasound by about 12 weeks. At birth, infants with DS have hypotonia, characteristic oblique palpebral fissures, flat faces, inner canthal folds, hyperflexible joints, a single palmar crease, and dysplastic middle phalanx of the fifth digit. More than half will have congenital cardiac malformations (about half have endocardial cushion defects and another 25% have ventricular septal defects). Although DS is universally associated with mental impairment, the degree of impairment varies.

Neurologic manifestations

In addition to the delayed mental development, social development is also delayed, resulting in common problems such as impulsive behavior, poor judgment, short attention span, and slow learning. As the child ages and becomes aware of his or her limitations, behavior may become increasingly unmanageable, with frequent outbursts noted. Independent of the degree of mental impairment early in life, those individuals with DS who survive into later adulthood are at increased risk for developing dementia, compared with individuals who do not have DS.

Head and neck abnormalities

Because patients with DS often have abnormalities of the head and neck, the anesthesia provider should assess any patient with DS seen in the preoperative clinic for these abnormalities (Box 207-1). Despite the many airway abnormalities described, patients with DS are typically not difficult to intubate, though they may be difficult to ventilate by mask. Cervical spinal malformations have been reported in association with trisomy 21, with 10% of patients having cervical spinal stenosis and 30% having atlantoaxial instability, although only 1% to 2% of these patients will become symptomatic.

Box 207-1 Anesthetic Concerns in Patients with Trisomy 21

Difficult intravenous access

Limited cognitive abilities

Generalized hypotonia

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