Advances in Genetic Testing Improve Diagnoses of Rare Conditions

By Joshua Baker, Merlene Peter and Vera Shively

In 1990, Samantha was first seen in the Division of Genetics, Birth Defects and Metabolism at Children's Memorial Hospital. She was not meeting the developmental milestones for children her age, and recently had a prolonged stay in the hospital. Was a genetic disorder the root cause of these problems? Her parents "wanted answers, to help with treatment for her, for planning her future and to see if her brother needed testing”. Unfortunately, a genetic diagnosis was not identified at the time. Flash forward 30 years, Children's Memorial is now Lurie Children's and Samantha received a long-awaited genetic diagnosis.

Genetic Testing Then and Now

When Samantha was seen in 1990, the genetic testing available to patients was quite limited. The practice of genetics relied heavily on clinical diagnosis of classically described syndromes. Diagnosing genetic conditions was limited by our knowledge of genes that cause health conditions and the technology to analyze genes. This unfortunately left many patients without a name for their condition or explanation for their medical concerns. A critical technology that would eventually lead to many of the advances in genetic testing seen today, polymerase chain reaction (PCR), was invented in 1983. However, in the 1990's PCR was used mostly to determine relationships, such as in paternity testing.

Today's genetic testing toolkit has greatly expanded and includes:

• Chromosomal microarray (CMA), sometimes called a molecular karyotype. It can identify much smaller changes in a chromosome than karyotypes of the 1990's. For example, CMA testing can detect extra (insertions) and missing (deletions) pieces of DNA across the entire genome. For example, Prader-Willi, DiGeorge, Williams and Angelman syndromes may be identified by CMA.
• Single gene testing looks for changes in one gene. This type of testing is done when a patient's symptoms are consistent with a monogenic, or single gene, condition. Examples include sickle cell disease or Marfan syndrome.
• Panel testing looks for changes in many genes in one test. Testing panels often cover categories of different types of medical concerns. Examples include genetic testing panels for epilepsy, hearing impairment and low muscle tone.
• Large-scale genetic testing analyzes the bulk of a person's DNA looking for variations that were not identified in other testing. This includes whole exome and whole genome sequencing.

Benefits of a Genetic Diagnosis

A genetic diagnosis may lead to improved management of symptoms, and the coordination and planning of care. In some cases, a genetic diagnosis may lead to testing of other family members. Patients and families united by having the same condition can organize, support one another and advocate for their affected family members. For school age children, a diagnosis may provide direction for accommodations to support their education, including the design of an Individualized Educational Program (IEP).

Genetics at Lurie Children’s

The Division of Genetics, Birth Defects and Metabolism provides care for patients with genetic and congenital disorders. Consultations with a multispecialty healthcare team, genetic screening and diagnostic testing, genetic counseling, and nutrition services for metabolic disorders are available for patients and their families. It is an exciting time in the field of genetics, with advancements leading to improved diagnosis and treatment options. The Genetics team at Lurie Children’s stays current in the latest developments, including involvement in clinical research trials to study potential new therapies for numerous genetic disorders.

More Information and Definitions

• Centers for Disease Control and Prevention (CDC) Genomics and Precision Health
• Different Types of Genetic Tests - MedlinePlus
• Gene: Long string of DNA with instructions for making a specific protein product that a living organism needs to grow and function
• Chromosome: Structures that hold many tightly packaged genes
• Genome: A complete set of an organism's DNA
• Exome: About 1 to 2% of the of the genome that codes for protein products.