Rudolph's Pediatrics, 22nd Ed.

CHAPTER 172. Principles of Care

Claire O. Leonard

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.

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

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 prior to using this screening test is currently recommended. The American College of Medical Genetics and other groups have developed guidelines for diagnostic evaluations under certain clinical circumstances.^3-5

Table 172-1. Conditions Suggesting a Genetic Disorder

Once a diagnosis has been made, either the specialist or the primary care physician should promptly inform the family. A pediatrician who knows the family may be in the best position to offer this service, but with rare and little-known conditions, access to the specialist or geneticist should also be made available. These informing sessions are critically important. Parents should be told together and in a private setting. Focus on the child and not the disease. Schedule adequate time. A management plan should be agreed on, and resources for family support and further counseling should be offered.

The Medical Home model provides a means for care coordination.⁶ There should be a written care plan, education for the family and patient, involvement with schools and community agencies, and referral to disease-specific support groups. Comanagement with a multidisciplinary team is often required. Close communication between providers is essential. The family should know who will be responsible for acute illnesses and for specific aspects of a child’s treatment to avoid confusion and delays in obtaining care. Parents should be provided with a document specifying the diagnosis, treatment information, potential acute complications, plans for emergency management, and sources for consultation. Expectations for the pediatrician are suggested in eTable 172-1 . Obtaining up-to-date information on a specific genetic condition may be a challenge. Online resources are quite helpful including, especially Mendelian Inheritance in Man (http://www.ncbi.nlm.nih.gov/omim) and Gene Clinics (http://www.geneclinics.org). Guidelines for management of specific disorders have been developed and are available.^7-9 In the case of progressive conditions in which death is likely during childhood, the pediatrician is often the most appropriate person to provide support for the family, including advice concerning post mortem diagnosis if necessary.

Genetic counseling is an important part of caring for a child with genetic disease. This is much more than recurrence risk counseling and requires ongoing attention over many years during the reproductive period of the family and the lifetime of the affected individual. Such counseling is a component of many multidisciplinary teams, but should be sought in every case.

Advocacy involves working with schools and referral to local and national support groups. The pediatrician should be the primary support for families and make referrals to subspecialists, including genetic counselors and obstetricians specializing in high-risk pregnancies when indicated.