X-Linked Intellectual Disability (XLID)
|Disorder||X-Linked Intellectual Disability (XLID)|
Intellectual disability (ID) is characterized by significant limitations in cognitive abilities and social/behavioral adaptive skills. It is estimated that 1-3% of the general population is affected with ID. Intellectual disability is one of the primary reasons for pediatric, neurologic, and genetic referrals.
|Indications||Males with intellectual disability (ID) who have normal chromosomes, microarray, and fragile X results and X-linked pattern family history
Males with ID in the presence or absence of other dysmorphic, neuromuscular, metabolic or behavioral phenotypes that distinguish the proband from unaffected males in the family
Females with a family history suggestive of an X-linked disorder and suspected to be carriers when no living males with ID are available to test
*For patients with a specific suspected XLID syndrome, individual gene sequencing should be considered first.*
Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.
|Detection||The current design of the XLID panel covers approximately 10% of coding genes found on the X chromosome. At present, genes that do no encode a protein product are not included in the panel. As new genes are implicated in XLID, updates will be made to the existing assay. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 25 basepairs of each intron/exon boundary for each gene. Promoter and 3’ untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations, but deletions in males should be readily apparent based on lack of amplification and sequence detection. Single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC provides high resolution testing for both X chromosome and whole genome applications. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures. This assay is expected to detect a mutation in approximately 25-30% of XLID patients.|
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.|
|Turnaround time||4 months|
|Prenatal testing||Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.|
|Cost||$5500 (includes clinical consultation and follow-up testing of appropriate family members)|
|Clinical Consultation||A distinguishing part of our service is a review of clinical information by GGC’s international team of XLID experts at no additional charge. Comments from the Intellectual Disabilities Evaluation and Advice System (IDEAS©) team will be included with the report and are expected to be particularly helpful in classifying variants of unknown clinical significance. To take advantage of this service, a one page phenotype information sheet must be completed and submitted along with the test requisition package.
Intellectual Disabilities Evaluation and Advice System (IDEAS©) Team
Roger E. Stevenson, M.D., Greenwood Genetic Center
R. Curtis Rogers, M.D., Greenwood Genetic Center
Alasdair Hunter, M.D., Greenwood Genetic Center Senior Scholar
John Graham, M.D., Cedar Sinai Medical Center
Giovanni Neri, M.D., Università of Cattolica del Sacro Cuore, Rome, Italy
Gillian Turner, M.D., Hunter Genetics, Newcastle, Australia
**The testing package also includes a copy of the reference book, Atlas of X-linked Intellectual Disability, by R.E. Stevenson, C.E. Schwartz, and R.C. Rogers (available Spring 2011)**
The Cytogenetics Lab provides high quality analysis for the detection of both constitutional chromosomal aberrations as well as abnormalities related to hematological malignancies