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The contribution of genetic variation to health and disease has
become increasingly clear as a result of our burgeoning understanding
of the human genome. Genomic medicine uses an understanding of the
individual’s genetic makeup to enhance the quality of medical
care, including presymptomatic identification and prevention, determination
of susceptibility to disease, selection of treatments, and individual
clinical care based on genotype. Most diseases fall somewhere on
a continuum from single-gene disorders, disorders with a major gene
effect, disorders with complex traits, and those with a predominantly
environmental causation. The majority of genetic disorders are multisystemic
in their manifestations. Most children with special health care
needs have disorders that are caused by mutations in single genes
or variations in chromosomes or that are heavily influenced by genetic
factors. Genetics can no longer be considered as only the identification
of rare syndromes and inborn errors of metabolism. Care for the
child with a genetic disorder involves five major activities—suspicion,
diagnosis, management, genetic counseling, and advocacy. These activities
require a partnership between the pediatrician, one or more specialists
or specialty teams, the family, and schools and other support services.
No physician can hope to recognize and personally manage all genetic
disorders, many of which are quite rare. Treatment for genetic conditions
is advancing rapidly, encompassing much more than the supportive
care previously available.
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Suspicion of a genetic condition must rest with the primary care
physician. Situations suggesting a genetic disorder are outlined
in Table 172-1. Single organ diseases or
birth defects may also be genetic or have a major genetic component.
Neuropsychiatric conditions such as autism spectrum disorder are
frequently genetic in causation. The American College of Medical
Genetics has published a detailed guide to indications for genetic
referral.1
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Once a genetic condition is suspected, a diagnostic evaluation
should be undertaken. Consultation with a geneticist or other specialist
is usually valuable to focus the testing. There are no generalized
screening tests for genetic disease. As for any clinical diagnosis, a
detailed history, family history, and physical examination are the
initial steps. The family history or specific biochemical or chromosomal
testing may supplement diagnostic information. Mutation analysis
(DNA testing) requires a definite clinical or biochemical diagnosis
or a suspicion of a specific diagnosis.1 Comparative
genomics uses a microarray of DNA segments to evaluate the patient
against a known normal panel.2 Although this testing may
be useful in some situations, the amount of genetic variability
in the population often makes interpretation of results difficult.
Exclusion of more easily diagnosed conditions ...