Clinical Pathology: Genetic Testing

• The diagnosis of Smith-Magenis syndrome (SMS) is based on clinical findings and confirmed by detection of an interstitial deletion of chromosome 17p11.2 by fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), or chromosomal microarray analysis (CMA).

• All deletions associated with SMS include a deletion of the RAI1 gene located on chromosome 17p11.2. This syndrome is characterized by distinctive facial features that progress with age, developmental delay, cognitive impairment, and behavioral abnormalities. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping, and generalized lethargy. The majority of these individuals have a mild-to-moderate range of intellectual disability.

• Approximately 90% of the cases with deletion of chromosome 17p11.2 can be detected using a locus-specific probe for the RAI1 gene. Sequence analysis is used in 5% to 10% of the suspected SMS patients when FISH testing is negative for the 17p11.2 deletion.

• Chromosome paint probes are fluorescently labeled libraries of DNA sequences derived from flow-sorted chromosomes and spectral karyotyping (SKY) is a FISH method that allows visualization of all the human chromosomes, each in a different fluorescent color.

• Recently, aCGH or CMA has become the diagnostic test of choice for detecting microdeletion syndromes.

Smith ACM, Boyd K, Elsea SH, et al: Smith-Magenis syndrome.In: GeneReviews at GeneTests: Medical Genetics Information Resource (online database). Seattle, WA, 1997–2011. Available at Accessed January 28, 2012.

Tools of human molecular genetics.: In: Nussbaum RL, McInnes RR, Willard HF, eds. Thompson & Thompson Genetics in Medicine. 7th ed. Philadelphia: Saunders Elsevier, 2007:41–58.

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