Test ID: FSMS
Smith-Magenis/Potocki-Lupski Syndromes, 17p11.2 Deletion/Duplication, FISH
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Aids in the diagnosis of 17p11.2 deletion (Smith-Magenis) and 17p11.2 duplication (Potocki-Lupski) syndromes, in conjunction with CMS/8696 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
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Fluorescence In Situ Hybridization (FISH)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
17p Duplication
17p11.2
17p11.2 Duplication
Potocki
Potocki-Lupski
RAI1
Smith-Magenis Syndrome
SMS
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.
Forms:
1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
2. If not ordering electronically, submit a Cytogenetics/AFP Congenital Disorders Request Form (Supply T238) with the specimen.
Advise Express Mail or equivalent if not on courier service.
Submit only 1 of the following specimens:
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20-25 mL
Collection Instructions:
1. Optimal timing for specimen collection is during 14 to 18 weeks of gestation, but specimens collected at other weeks of gestation are also accepted. Provide gestational age at the time of amniocentesis.
2. Discard the first 2 mL of amniotic fluid.
Additional Information:
1. Place the tubes in a Styrofoam container (Supply T329).
2. Fill remaining space with packing material.
3. Unavoidably, about 1% to 2% of mailed-in specimens are not viable.
4. Bloody specimens are undesirable.
5. If the specimen does not grow in culture, you will be notified within 7 days of receipt.
6. Results will be reported and also telephoned or faxed, if requested.
Specimen Type: Autopsy
Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline
Specimen Volume: 4-mm diameter
Collection Instructions:
1. Wash biopsy site with an antiseptic soap.
2. Thoroughly rinse area with sterile water.
3. Do not use alcohol or iodine preparations.
4. Biopsy specimens are best taken by punch biopsy to include full thickness of dermis.
Specimen Type: Blood
Container/Tube: Green top (sodium heparin)
Specimen Volume: 5 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Other anticoagulants are not recommended and are harmful to the viability of the cells.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20-25 mg
Collection Instructions:
1. Collect specimen by the transabdominal or transcervical method.
2. Transfer chorionic villi to a Petri dish containing transport medium (Supply T095).
3. Using a stereomicroscope and sterile forceps, assess the quality and quantity of the villi and remove any blood clots and maternal decidua.
Specimen Type: Fixed cell pellet
Container/Tube: Sterile container with a 3:1 fixative (methanol:glacial acetic acid)
Specimen Volume: Entire specimen
Specimen Type: Products of conception or stillbirth
Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline
Specimen Volume: 1 cm(3) of placenta (including 20 mg of chorionic villi) and a 1-cm(3) biopsy specimen of muscle/fascia from the thigh
Collection Instructions: If a fetus cannot be specifically identified, collect villus material or tissue that appears to be of fetal origin.
Additional Information: Do not send entire fetus.
Forms: Final Disposition of Fetal/Stillborn Remains (if fetal specimen is sent) in Special Instructions
Specimen Type: Skin biopsy
Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline
Specimen Volume: 4-mm diameter
Collection Instructions:
1. Wash biopsy site with an antiseptic soap.
2. Thoroughly rinse area with sterile water.
3. Do not use alcohol or iodine preparations.
4. A local anesthetic may be used.
5. Biopsy specimens are best taken by punch biopsy to include full thickness of dermis.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | Clotted blood |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Refrigerated | ||
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/8696 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.
Interpretation Provides information to assist in interpretation of the test results
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.
Supportive Data
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: Clinical cytogenetics. In Laboratory Medicine. 2nd edition. Edited by K McClatchey. Baltimore, Williams & Wilkins, 2002, Chapter 26
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
Method Description Describes how the test is performed and provides a method-specific reference
Identification of deletions or duplications of 17p11.2 associated with Smith-Magenis/Potocki-Lupski syndromes is based on FISH analysis of the critical RAI1 region (RAI1)on the short arm of chromosome 17 (17p11.2). Metaphase cells are examined for the presence of 2 critical region loci at 17p11.2 (orange signal) and the control probe (47G8) at 17q21.1 (green signal). In metaphase cells with a deletion, the abnormal (deleted) chromosome 17 will exhibit only a control probe signal, while signals for both the critical region and control probes will be present on the normal chromosome 17 homolog. If metaphase analysis is normal, 200 interphase nuclei are scored for the presence of 3 orange signals, which is consistent with duplication (RP11-1149K20).(Crifasi PA, Michels VV, Driscoll DJ, et al: DNA fluorescent probes for diagnosis of velocardiofacial and related syndromes. Mayo Clin Proc 1995;70[12]:1148-1153)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
88271 x 2-DNA probe, each
88273-Chromosomal in situ hybridization
88291-Interpretation and report
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 23231 | Specimen | 31208-2 |
| 23232 | Specimen ID | N/A |
| CG209 | Source | N/A |
| 23234 | Order Date | N/A |
| CG211 | Reason For Referral | 42349-1 |
| 23236 | Method | In Process |
| 23237 | Result | In Process |
| 23238 | Interpretation | 69965-2 |
| 23239 | Amendment | In Process |
| 23240 | Consultant | N/A |
| 23241 | Released Date | N/A |
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