Ordering
  • Test code: 02311
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Loeys-Dietz Syndrome Panel

Test description

This test is for individuals with a clinical diagnosis of Loeys-Dietz syndrome (LDS). The primary panel includes 4 genes that have been definitively associated with LDS and 2 genes that clinically overlap with LDS.

Individuals presenting with features of a connective tissue condition with vascular involvement may benefit from diagnostic genetic testing to confirm diagnosis, clarify risks, or inform management. Confirming a diagnosis of LDS is particularly important because individuals with LDS are at risk for aortic dissections at smaller aortic dimensions than individuals with other forms of connective tissue disorders, and the locations of aneurysms are more varied.

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Primary panel (6 genes)

FBN1 SMAD3 TGFB2 TGFB3 TGFBR1 TGFBR2

Alternative tests to consider

LDS can also be ordered as part of a broader panel to test for aortopathy disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate. This broader panel can be ordered at no additional charge.

LDS, thoracic aortic aneurysms and aortic dissections (TAAD), multiple self-healing squamous epithelioma, Marfan syndrome.

Clinical subtypes: LDS1, LDS2, LDS3, LDS4, LDS5.

Loeys-Dietz syndrome (LDS) is a connective tissue condition that typically involves the vascular, cutaneous, craniofacial, and skeletal systems. The primary vascular features associated with LDS include early-onset aneurysms (dilations) of the aorta and other arteries, as well as arterial tortuosity. Skeletal features can include cervical instability, scoliosis, joint laxity, clubfoot, and chest wall deformities. Many individuals with LDS also have craniofacial involvement that can include widely spaced eyes, a bifid uvula, and/or cleft palate.

The presentation of LDS can appear similar to Marfan syndrome. Marfan syndrome is a connective tissue disorder involving the cardiovascular, skeletal, pulmonary and ocular systems. Common features include tall stature, aortic aneurysm with risk of dissection, mitral valve prolapse, ectopia lentis, myopia, and retinal detachment. Other features may include scoliosis and chest wall deformities, pneumothorax, and dural ectasia. Marfan syndrome and other FBN1-related disorders demonstrate clinical variability, ranging from severe, multi-system features in the neonatal period to an isolated feature or mild symptoms at any age.

Approximately 80%-90% of individuals with characteristic features of LDS are expected to have a pathogenic variant identified in one of the genes on this panel. The majority of individuals with LDS will have a pathogenic variant identified in TGFBR2. However, a negative genetic test result does not rule out the possibility that an individual may have LDS.

Gene% of LDS cases attributed
TGFBR255-60%
TGFBR120-25%
SMAD35-10%
TGFB25-10%
TGFB31-5%

LDS is an autosomal dominant condition. However, approximately 75% of individuals with LDS have a de novo pathogenic variant that is not inherited from either parent.

The penetrance for LDS is not known. Clinical presentation can vary between individuals in the same family. Major lifetime risks associated with LDS include aortic dissection, cervical instability, rupture of the spleen or bowel, and uterine rupture during pregnancy in women with LDS.

The prevalence of LDS is currently unknown.

This test may be considered for individuals presenting with several characteristic features of LDS, including arterial tortuosity, aneurysms, hypertelorism (widely spaced eyes), and a bifid or broad uvula.

For links to published management guidelines, please refer to our Management guidelines page.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
FBN1 NM_000138.4
SMAD3 NM_005902.3
TGFB2 NM_003238.3
TGFB3 NM_003239.3
TGFBR1 NM_004612.2
TGFBR2 NM_003242.5