Medical Professional Publications

When Genetic Testing Reveals Surprising Results

Case Studies Highlight the Power of Testing and the Dichotomy of Unexpected Diagnosis

Genetic testing can help physicians understand and clarify why patients have particular symptoms, but what if testing reveals an unanticipated and life-threatening condition? A case series from Nationwide Children’s emphasizes this possibility, as genetic testing in three patients unexpectedly revealed that each child had a deletion within the gene associated with Duchenne and Becker muscular dystrophies. The deletions were detected by a method known as array comparative genomic hybridization (aCGH or microarray).

Array CGH has become the standard of care to evaluate patients for genomic imbalance.  With a greater sensitivity than traditional chromosome analysis, as well as a rapid turnaround time, aCGH serves as a clinically useful tool in assisting with genetic diagnoses.  Microarray testing may be useful when a patient presents with nonspecific findings which are not easily attributable to a specific genetic syndrome, such as developmental delay or dysmorphic features.

“When clinicians order microarray, they are most often searching for genetic clues to explain their current clinical findings,” said Julie Gastier-Foster, PhD, director of the Cytogenetics/Molecular Genetics Laboratory at Nationwide Children’s.  “The challenge with microarray results is when the findings suggest a risk for a disease for which they are showing no outward sign.”

Such was the case for three patients, as described in the case series in the American Journal of Medical Genetics.  Three unrelated patients were referred for microarray analysis to the Cytogenetics/Molecular Genetics Laboratory at Nationwide Children’s because each had non-specific physical attributes including delays, unusual facial features and low muscle tone.  Testing unexpectedly revealed that each child had a deletion within the dystrophin gene.  Mutations of the dystrophin gene are associated with a group of diseases known as the dystrophinopathies.  Included within this group are Duchenne and Becker Muscular Dystrophies and X-linked dilated cardiomyopathy. No patient was suspected of manifesting symptoms consistent with a dystrophinopathy at the time of testing, and such symptoms may not be readily apparent for several years. 

The implications of detecting a dystrophin gene deletion are certain to be life-changing for the patient and family. “In cases such as these, having a diagnosis prior to the manifestation of the full phenotype is certain to impact clinical care,” said Dr. Gastier-Foster.  While there is no cure at present for a dystrophinopathy, early detection may enable the patient to receive more proactive treatment and may allow for early medical intervention in at-risk family members, including access to counseling and carrier testing.

“As microarray testing continues to be the assay of choice in patients with common but nonspecific symptoms, we are certain to continue to detect unexpected findings among patients,” said Dr. Gastier-Foster.  “As this technology becomes more sensitive, clinicians may find it more time consuming and challenging to counsel families about the potential outcomes prior to testing.”

Cottrell CE, Prior TW, Pyatt R, Astbury C, Reshmi S, Bartholomew D, Atkin J, Manickam K, Thrush DL, Pastore M, Mendell J, Tsao CY, Al-Dahhak R, Newmeyer A, Gastier-Foster JM. Unexpected detection of dystrophin gene deletions by array comparative genomic hybridization. Am J Med Genet A. 2010 Sep;152A(9):2301-7.

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