Connective Tissue Disease Panel

Ordering Information

Clinical Description

Heritable disorders of connective tissue are a clinically and genetically diverse group of conditions affecting the strength, elasticity, and integrity of skin, joints, blood vessels, and other connective tissue structures. Clinical features may include joint hypermobility, skin hyperextensibility and fragility, vascular fragility with risk of arterial aneurysm or dissection, ocular abnormalities such as lens dislocation, and skeletal findings including pectus deformities, scoliosis, and arachnodactyly.

The genes on this panel are associated with a range of disorders, including Ehlers-Danlos syndrome and its subtypes as classified by the 2017 International Classification of the Ehlers-Danlos Syndromes (1), Marfan syndrome, Loeys-Dietz syndrome and other TGF-β pathway-related aortopathies, cutis laxa, pseudoxanthoma elasticum, osteogenesis imperfecta, Stickler syndrome, arterial tortuosity syndrome, and related conditions.

The underlying disease mechanisms are diverse and include defects in structural extracellular matrix components such as collagen, elastin, and fibrillin; dysregulation of TGF-β signaling; impaired collagen processing or crosslinking; and lysosomal or metabolic dysfunction affecting connective tissue homeostasis. Inheritance may be autosomal dominant, autosomal recessive, or X-linked, depending on the specific gene and condition.

The genes on this panel were specifically selected for their established association with heritable connective tissue disorders. Identification of a pathogenic variant may establish a molecular diagnosis, inform prognosis and management (including surveillance for vascular or ocular complications) and facilitate genetic counseling for the patient and their family members.

Conditions covered by this panel include: Aortopathy and vascular: Marfan syndrome, Loeys-Dietz syndrome types 1 through 6, familial thoracic aortic aneurysm and aortic dissection, multisystemic smooth muscle dysfunction syndrome, arterial tortuosity syndrome, Shprintzen-Goldberg syndrome, Meester-Loeys syndrome Ehlers-Danlos syndromes: classic, classic-like 2, vascular, cardiac valvular, dermatosparaxis, kyphoscoliotic, musculocontractural, periodontal, spondylodysplastic, and spondylocheirodysplastic types, plus COL1A1-related and COL1A2-related EDS Bone and skeletal: osteogenesis imperfecta, Stickler syndrome, achondrogenesis type II, Kniest dysplasia, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, fibrodysplasia ossificans progressiva, and other skeletal dysplasias Skin and connective tissue: cutis laxa (multiple types), pseudoxanthoma elasticum, stiff skin syndrome, Buschke-Ollendorff syndrome Ocular: Weill-Marchesani syndrome, brittle cornea syndrome, isolated ectopia lentis, anterior segment dysgenesis Other: Menkes disease, classic homocystinuria, Birt-Hogg-Dube syndrome, polycystic kidney disease type 2, and additional conditions listed in the full test description

One or more genes on this panel are also associated with other conditions for which a predisposition to, or carrier status of, may be identified, including complement component C1s deficiency, demyelinating hereditary motor and sensory neuropathy, developmental and epileptic encephalopathy 93, distal spinal muscular atrophy type 3, familial spontaneous pneumothorax, neuronal intestinal pseudoobstruction, juvenile polyposis / hereditary hemorrhagic telangiectasia syndrome, age-related macular degeneration, nonsyndromic hearing loss, periventricular nodular heterotopia, pulmonary arterial hypertension, and spastic paraplegia type 9B. Note: This panel does not include TNXB. Hypermobile EDS (hEDS) currently has no established monogenic etiology and is not covered by this panel.

References Malfait F, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552. PMID: 28306229.