Our laboratory is excited to announce the newly redesigned next generation sequencing Skeletal Dysplasia Testing Panel. In a continuing effort to provide prenatal patients with early genetic testing options, we have developed this panel as an option for pregnancies with an increased nuchal translucency in the first trimester and/or ultrasound findings suggestive of a skeletal dysplasia detected during the first or second trimester.
The Skeletal Dysplasia Testing Panel uses next generation sequencing, with confirmation by Sanger sequencing, to test for 463 mutations in eight genes known to be associated with prenatal and/or perinatal onset skeletal dysplasias. A summary of the genes tested and the conditions associated with mutations in each gene is included below. It is difficult to calculate a specific detection rate for each condition included in a targeted panel of this kind; however, the proportion of reported disease-causing mutations for each gene tested is as high as 99%, depending on the gene and condition. The sensitivity of this technology is >99%, with an analytic specificity of >93%.
Summary of the mutations included in the Skeletal Dysplasia Testing Panel:
The Skeletal Dysplasia Testing Panel may also be used in conjunction with the next generation sequencing Noonan Syndrome Testing Panel for fetuses with increased nuchal translucency and normal karyotype. A number of studies have recently reported an association between increased nuchal translucency measurements and skeletal dysplasias, however we know it can be quite difficult to make a specific diagnosis based on ultrasound findings alone, especially early in the pregnancy. The Skeletal Dysplasia Testing Panel was designed to assist providers in making a differential diagnosis prenatally in order to provide patients with a more comprehensive prognosis and an accurate recurrence risk calculation.
Billing Items:
All samples must include patient clinical information relevant to the testing being ordered. This information helps us to work with the patient's insurance provider when securing coverage. We also request a copy (front and back) of their insurance card if the patient is going through private insurance. In addition, we are now offering an institutional billing option as well as discounted patient pricing. For more information please contact our office.
CPT Codes:
Skeletal Dysplasia Panel: 81404x2, 81405x3, 81406x2, 81407x1
Maternal cell contamination studies: 81265, 81266 (if twins)
Specimen and Shipping Requirements:
For our next-generation sequencing testing panels, we are able to accept:
- Direct chorionic villi: 15-20mg
- 2 T-25 flasks of confluent fetal cells
- Extracted DNA: 3 micrograms in a minimum of 50 uL
Maternal cell contamination studies are also required prior to all next-generation sequencing tests; therefore a maternal blood sample is also required.
Unfortunately, we are unable to perform testing on direct amniotic fluid samples at this time, due to low concentration of DNA present in these samples.
Additional specimen must be held for back-up culture at another facility.
Please note: If the sample volume is less than requested, tissue culture will be required. This will delay the processing of genetic testing and no guarantees can be made if the sample fails to grow in culture. We will notify the referring physician/counselor/laboratory if the sample is inadequate.
Shipping Requirements
Ship overnight at ambient temperature to arrive Monday-Friday. A completed requisition form, billing form, and consent form must be included with the sample. Shipping costs are the responsibility of the sender.
Ship to: Insight Medical Genetics, 680 N. Lake Shore Drive, Suite 1230, Chicago, IL 60611 Telephone number: 312-981-4400
Turnaround Time: Approximately up to 3 weeks.
References
Bilardo CM, Timmerman E, Pajkrt E, and van Maarle M. (2010) Increased nuchal translucency in euploid fetuses- what should we be telling the parents? Prenatal Diagnosis 30: 93-102.
Chard R. (2010) Genetic Syndromes Associated with Increased NT Measurements: Skeletal Dysplasias. The NT Examiner Summer 2010 Edition.
Khalil A, Pajkrt E, Chitty LS. (2011) Early prenatal diagnosis of skeletal anomalies. Prenatal Diagnosis 31:115-124.
Ngo C, Viot G, Aubry MC, Tsatsaris V, Grange G, Cabrol D, and Pannier E. (2007) First-trimester ultrasound diagnosis of skeletal dysplasia associated with increased nuchal translucency thickness. Ultrasound in Obstetrics and Gynecology 30:221-0226.
Schramm T, Gloning KP, Minderer S, Daumer-Hass C, Hortnagel K, Nerlich A, and Tutschek B. (2009) Prenatal sonographic diagnosis of skeletal dysplasias. Ultrasound in Obstetrics and Gynecology 34:160-170.
Souka AP, Kaisen berg CS, Hyett JA, Sonek JD, and Nicolaides KH. (2005) Increased nuchal translucency with normal karyotype. American Journal of Obstetrics and Gynecology 192: 1005-21.
Souka AP, Krampl E, Bakalis S, Health V, and Nicolaides KH. (2001) Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester. Ultrasound in Obstetrics and Gynecology 18:9-17.
Tonni G, et al. (2005) First-trimester Increased Nuchal Translucency Associated with Fetal Achondroplasia. American Journal of Perinatology 22(3)145-148.
Witters I, Moerman P, Fryns JP. (2008) Skeletal dysplasias: 38 prenatal cases. Journal of Genetic Counseling 19(3):267-75.