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 four genes that have been definitively associated with LDS.

In addition to the primary panel, clinicians can also choose to include genes associated with connective tissue and aortopathy conditions that have strong clinical overlap with LDS, specifically TGFB3 and FBN1. If clinically indicated, these genes can be added onto the primary panel at no additional charge.

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 (Marfan syndrome), and the locations of aneurysms are more varied. Confirming a diagnosis of LDS through genetic testing can therefore prompt comprehensive imaging of the entire aorta and other arteries, enabling early and more aggressive surgical intervention of aneurysms as needed.

Order test

Primary panel (4 genes)


Add-on clinically-overlapping genes (2 genes)

The clinical presentation of LDS can overlap and be difficult to distinguish from other types of connective tissue conditions and aortopathies. Specifically, there is strong clinical overlap between LDS and the disorders caused by the TGFB3 and FBN1 genes. If clinically indicated, these genes can be added at no additional charge.


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.

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

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.

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

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

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, NM_001024847.2