MULTIPLE EXOSTOSES
FISH ANALYSIS

The Kleberg Cytogenetics Laboratory offers a fluorescence in situ hybridization (FISH)-based assay for identifying the microdeletion on 8q24.1 associated with the multiple exostosis I locus and the microdeletion on 11p11.2 associated with the multiple exostosis II locus. Both conditions exhibit significant phenotypic variability and most likely represent contiguous gene deletion syndromes, with the deletion of 8q24.1 causing Langer-Giedion syndrome (LGS) and the deletion on 11p11.2 causing the Potocki-Shaffer mental retardation syndrome.

Clinical Features:

Individuals with hereditary multiple exostosis (HME) typically have cartilage-capped bony growths (exostoses) which may grow until skeletal maturity occurs. Bowing may appear in the forearms or lower legs and the knees are often affected. HME is an autosomal dominant disorder with highly variable clinical features. Individuals with multiple exostoses, unusual facial features and mental retardation may have Langer-Giedion syndrome (LGS). The features of the Potocki-Shaffer syndrome (PSS) include multiple exostoses, biparietal foramina, dysmorphic features and mental retardation.

Reasons for Referral:

FISH can be used to detect deletions in patients with a suspected diagnosis of HME and/or LGS or PSS. Prenatal diagnosis may be performed if an affected family member has been studied in our laboratory and shown to have a deletion detectable by FISH. Please call regarding all prenatal samples.

Testing Methodology:

FISH is the application of fluorescently labeled DNA molecules to metaphase chromosomes and interphase nuclei for the detection of chromosome abnormalities and alterations. It is a rapid, reliable and direct approach for identifying patients with microdeletions or microduplications. FISH analysis for multiple exostosis is performed on metaphase chromosomes. The absence of a hybridization signal indicates a deletion. This FISH-based assay utilizes a dual-probe system that detects the presence or absence of the EXT1 gene in 8q24.1 and the EXT2 gene in 11p11.2. Patients with isolated HME who are not deleted by FISH may have mutations in either EXT1 or EXT2 not detectable with this methodology.

Specimen Requirements:

Whole blood in sodium heparin (green-top) tubes:
Newborn (< 3 months): Minimum 0.5 -2.0 CC
Adult/Child: Minimum 3.0 -5.0 CC

Shipping and Handling:

All tubes must be labeled with the patient's testname and date of birth, and a completed requisition form must accompany each sample. If the laboratory is billing the patient's insurance, please enclose a copy of the insurance card. Ship specimens for overnight delivery at ambient temperature. Please notify the laboratory of incoming samples.

Turnaround Time:

7-10 days

CPT Codes and Prices:

Multiple Exostoses (includes Ext 1 & Ext 2): 88230, 88273, 88271x2, 88291, 88280
Multiple Exostoses 1: 88230, 88273, 88271, 88291
Multiple Exostoses 2 (Potocki/Shaffer): 88230, 88273, 88271, 88291

References:

1. Ahn, et al. (1995) Nat. Genet. 11: 137-143.
2. Potocki, et al. (1996) Am. J. Med. Genet. 62: 319-325.

Forms:

>> Cytogenetics Requisition
>> Prenatal Requisition

Test Codes:

Multiple Exostoses (includes Ext 1 & Ext 2): 8435
Multiple Exostoses 1: 8472
Multiple Exostoses 2 (Potocki/Shaffer): 8473