Smith-Magenis/Potocki-Lupski Syndromes, 17p11.2 Deletion/Duplication, FISH
Aids in the diagnosis of 17p11.2 deletion (Smith-Magenis) and 17p11.2 duplication (Potocki-Lupski) syndromes, in conjunction with CMS / Chromosome Analysis, for Congenital Disorders, Blood
Detecting cryptic translocations involving 17p11.2, including the RAI1 critical region, that are not demonstrated by conventional chromosome studies
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Smith-Magenis syndrome is associated with a deletion of the proximal short arm of chromosome 17, including the critical RAI1 gene region. Although the phenotype is variable, the syndrome can be suspected in patients with failure to thrive, brachycephaly (short head), prominent forehead, microcephaly (small head), flat and broad midface, broad nasal bridge, strabismus, myopia, malformed ears, high and cleft palate, prognathism (protruding mandible), short and broad hands and feet, scoliosis (laterally curved spine), and cryptorchidism (undescended testes). Unusual features of the syndrome include specific self-destructive behavior, including insertion of foreign objects into bodily orifices, pulling out fingernails and toenails, and sleep abnormalities (especially disturbed rapid eye movement sleep). Mental retardation is variable but usually severe with seizures and hyperactivity.
Patients with duplications of this region (Potocki-Lupski syndrome) tend to have a milder but overlapping phenotype.
FISH studies are highly specific and do not exclude other chromosome abnormalities. For this reason, we recommend that patients suspected of having Smith-Magenis or Potocki-Lupski syndromes also have conventional chromosome studies (CMS / Chromosome Analysis, for Congenital Disorders, Blood) performed to rule out other chromosome abnormalities or translocations.
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.
Any individual with a normal signal pattern (2 signals for RAI1) in each metaphase is considered negative for a deletion or duplication in the region tested by this probe.
Any patient with a FISH signal pattern indicating loss of the RAI1 critical region will be reported as having a deletion of the regions tested by this probe. This is consistent with a diagnosis of 17p11.2 deletion (Smith-Magenis) syndrome.
Any patient with a FISH signal pattern indicating additional critical region signals will be reported as having a duplication of the regions tested by this probe. This is consistent with a diagnosis of 17p11.2 duplication (Potocki-Lupski) syndrome.
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 FDA, it is important to confirm 17p11.2 deletion/duplication (Smith-Magenis/Potocki-Lupski) syndrome diagnoses by other established methods, such as clinical history or physical examination.
FISH analysis was performed on a series of 50 peripheral blood samples and results were compared to previous chromosomes, FISH (using the SMS probe from Abbott Molecular), and aCGH studies. The SMS probe previously used does not include the RAI1 critical region. Using a laboratory-developed probe for the Smith-Magenis/Potocki-Lupski syndromes at 17p11.2, which includes the RAI1 critical region, FISH analysis confirmed deletion of the critical region in 13 patients previously known to have a phenotype consistent with Smith-Magenis syndrome and deletion of 17p11.2. Duplication of the critical region was confirmed in 2 patients known to have a phenotype consistent with Potocki-Lupski syndrome and 17p11.2 duplication. No deletions or duplications of the RAI1 critical region were identified in 35 patient specimens previously shown to be normal by karyotype or FISH analysis.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Van Dyke DL, Wiktor A: Chapter 26: Clinical cytogenetics. In Laboratory Medicine. Second edition. Edited by K McClatchey. Baltimore, Williams and Wilkins, 2002
2. Juyal RC, Greenberg F, Mengden GA, et al: Smith-Magenis syndrome deletion: a case with equivocal cytogenetic findings resolved by fluorescence in situ hybridization. Am J Med Genet 1995;58:286-291
3. Potocki L, Chen KS, Park SS, et al: Molecular mechanism for duplication 17p11.2-the homologous recombination reciprocal of the Smith-Magenis microdeletion. Nat Genet 2000;24:84-87
4. Vlangos CN, Wilson M, Blancato J, et al: Diagnostic FISH probes for del(17)(p11.2p11.2) associated with Smith-Magenis syndromes should contain the RAI1 gene. Am J Med Genet 2005;132A:278-282
5. Elsea SH, Girirajan S: Smith-Magenis Syndrome. Eur J Hum Genet 2008;16:412-421