Melissa P. Wasserstein, MD, Chief of Pediatric Genetic Medicine at the Children’s Hospital at Montefiore, New York City discusses the challenges of diagnosing rare diseases. She uses Krabbe disease, Nieman-Pick disease, and 22q11.2 deletion syndrome as examples.
Typically, a physician may suspect a diagnosis of a genetic condition on the basis of a person’s physical characteristics and family history, or on the results of a screening test. Genetic testing is one of several tools that doctors use to diagnose genetic conditions. The approaches to making a genetic diagnosis include:
A physical examination: Certain physical characteristics, such as distinctive facial features, can suggest the diagnosis of a genetic disorder. A geneticist will do a thorough physical examination that may include measurements such as the distance around the head (head circumference), the distance between the eyes, and the length of the arms and legs. Depending on the situation, specialized examinations such as nervous system (neurological) or eye (ophthalmologic) exams may be performed. The doctor may also use imaging studies including x-rays, computerized tomography (CT) scans, or magnetic resonance imaging (MRI) to see structures inside the body.
Personal medical history: Information about an individual’s health, often going back to birth, can provide clues to a genetic diagnosis. A personal medical history includes past health issues, hospitalizations and surgeries, allergies, medications, and the results of any medical or genetic testing that has already been done.
Family medical history: Because genetic conditions often run in families, information about the health of family members can be a critical tool for diagnosing these disorders. A doctor or genetic counselor will ask about health conditions in an individual’s parents, siblings, children, and possibly more distant relatives. This information can give clues about the diagnosis and inheritance pattern of a genetic condition in a family.
Laboratory tests, including genetic testing: Molecular, chromosomal, and biochemical genetic testing are used to diagnose genetic disorders. Other laboratory tests that measure the levels of certain substances in blood and urine can also help suggest a diagnosis.
Genetic testing is currently available for many genetic conditions. However, some conditions do not have a genetic test; either the genetic cause of the condition is unknown or a test has not yet been developed. In these cases, a combination of the approaches listed above may be used to make a diagnosis. Even when genetic testing is available, the tools listed above are used to narrow down the possibilities (known as a differential diagnosis) and choose the most appropriate genetic tests to pursue.
A diagnosis of a genetic disorder can be made anytime during life, from before birth to old age, depending on when the features of the condition appear and the availability of testing. Sometimes, having a diagnosis can guide treatment and management decisions. A genetic diagnosis can also suggest whether other family members may be affected by or at risk of a specific disorder. Even when no treatment is available for a particular condition, having a diagnosis can help people know what to expect and may help them identify useful support and advocacy resources.