Williams Syndrome, 7q11.23 Deletion, FISH
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Williams syndrome (WS) is a genetic disorder that occurs in 1/20,000 to 1/50,000 live births. Although WS is typically a sporadic disorder, familial cases have been reported.
WS is characterized by a variable combination of cardiovascular abnormalities, connective tissue abnormalities, distinct facial features, infantile hypercalcemia, mental retardation, and characteristic social interactions such as extreme friendliness and attention-deficit hyperactivity disorder.
Isolated congenital narrowing of the ascending aorta is common in WS patients and results in a separate syndrome called supravalvular aortic stenosis (SVAS).
WS is a contiguous gene deletion syndrome, caused by deletion of several genes on chromosome 7q. One gene that often is deleted in WS is the elastin gene, which causes SVAS and other cardiovascular disease in these patients. This association was described by Ewart et al (1993) who identified hemizygosity of the elastin gene in WS and SVAS.
The elastin gene, ELN, has been mapped to 7q11.23 (Williams syndrome chromosome region, and is reportedly hemizygous in up to 96% of patients with WS. The deletion of an elastin gene locus cannot be detected by conventional high-resolution chromosome analysis in the vast majority of cases due to the small size of this deletion. Nickerson et al used molecular methods to detect a deletion of the elastin gene in 91% (39/43) of WS patients.
Detecting deletions of the elastin gene at 7q11.23
Diagnosis of Williams syndrome, when used in combination with high-resolution chromosome studies and clinical evaluation
An interpretive report is provided.
The use of high-resolution chromosome studies and FISH for Williams syndrome chromosome region should diagnose about 96% of Williams syndrome patients and, at the same time, identify any other chromosome anomalies.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because this FISH test is not approved by the Food and Drug Administration it is important to confirm Williams syndrome (WS) by other established methods, such as clinical evaluation.
In up to 1% of patients, WS is caused by a gene mutation within or near the elastin gene. These mutations would not be detected by this FISH test. FISH testing involves a DNA probe that detects only large deletions including this entire gene and the DNA probe, small deletions or mutations may give normal results by FISH.
Patients with a deletion outside of the elastin gene could display normal development of connective tissue, including the heart, but have other features of WS.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Ewart AK, Morris CA, Atkinson D, et al: Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet 1993;5:11-16
2. Jalal SM, Crifasi PA, Karnes PS, Michels VV: Cytogenetic testing for Williams syndrome. Mayo Clin Proc 1996;71:67-68
3. Lowery MC, Morris CA, Ewart AK, et al: Strong correlation of elastin deletions, detected by FISH, with Williams syndrome, evaluation of 235 patients. Am J Hum Genet 1995;57:49-53
4. Morris CA, Demsey SA, Leonar CO, et al: Natural history of Williams syndrome. J Pediatr 1988;113:318-326
5. Olson TM, Michels VV, Lindor NM, et al: Autosomal dominant aortic stenosis: localization to chromosome 7. Hum Mol Genet 1993;2:869-873