USA Surgery Today

In autosomal recessive (AR) conditions, both genes at a locus are abnormal, which results in the absence of normal protein product. Abnormal genes are inherited from both parents each of whom has one normal and one abnormal gene (called carriers), but show no clinical evidence of the condition themselves. Many AR conditions are due to the absence of an enzyme; carriers often have one-half the normal amount of enzyme, but this amount is sufficient so they demonstrate no signs or symptoms of the condition. Two carriers of an AR condition have a 25% risk of having an affected child with each pregnancy . It has been estimated that each of us carries 6 to 10 recessive genes. Therefore, these conditions occur more frequently among inbred groups and consanguineous matings, because related individuals are more likely to have inherited the same abnormal recessive gene.

The purpose of this section is to review aspects that require emphasis for the treatment of children with physical disabilities.

The principles on which decision making are based for children with disabilities are the same as for typical children: autonomy, beneficence, justice, nonmaleficence, veracity, and fidelity (1). Parents and legal guardians are recognized legally as substitute decision makers for neurologically impaired children.

It is important for pediatricians and pediatric surgeons to discuss openly and forthrightly their approaches toward the treatment of severely cognitively impaired children. Agreement on principles is essential to provide best care. When conflicts arise, helpful mediation by a single member of a hospital’s Ethics Committee can be useful, without being cumbersome and time consuming. If true conflicts exist over specific cases, then formal consideration by the hospital Ethics Committee can help with resolution (2), although this is rarely required.

The dose of bacterial contamination is a key determinant of infection. Quantitatively, if a surgical site is contaminated with more than 10⁵ microorganisms per gram of tissue, then the risk of SSI is markedly increased (4). The dose of microorganisms required to produce infection may be considerably lower in the presence of foreign material (i.e., 100 staphylococci per gram of tissue introduced on silk suture) (5). The number of organisms required to produce clinical infection predictably decreases in states of diminished host resistance.

The virulence of a microorganism refers to its ability to invade, damage, or survive in host tissue. Some gram-negative bacteria elaborate endotoxin that causes no local injury, but stimulates cytokine production. Cytokines trigger the systemic inflammatory response syndrome (SIRS), which may lead to organ failure. Other bacteria possess cell surface polysaccharide capsules that inhibit phagocytosis, an early host defense to microbial contamination.

In an autosomal (non“sex-linked) dominant (AD) condition, an abnormality in one member of a gene pair is sufficient to cause the condition. Although the strict definition of a dominant condition specifies that the heterozygous individual is indistinguishable from the homozygous-affected individual, this is often not the case. Instead, frequently the homozygote is more severely affected than the heterozygote.

Most dominant conditions involve the formation of structural proteins. Changes in one gene of a pair can result in a phenotype through loss of function, where the abnormal gene produces an absent gene product. Because only one of the pair of genes is working properly, only half of the normal amount of product is formed. Another way that a dominant gene can cause a genetic condition is through a gain of function, where the new protein takes on a deleterious function (9).

Individuals with a dominant condition have a 50% risk of passing the condition on to their offspring, and males and females are affected with equal frequency. Patients with AD conditions often have other affected family members. Families in which an AD condition is segregating often show a vertical pattern of transmission, with multiple generations affected (Fig. 2-1). Because dominant conditions have a wide variability in expression, a parent might not be identified as having the condition unless he or she is carefully examined for minor manifestations. In some cases, neither parent is affected and the child is a new mutation. The frequency of these new mutations increases with increasing paternal age. Rarely, an individual in an autosomal dominant pedigree who must be a carrier of the gene based on the inheritance pattern shows no manifestations. This is termed incomplete penetrance.

An example of a common AD condition is neurofibromatosis 1 (NF1) (MIM 162200), which occurs in 1 in 3,000 births.