What is Connective Tissue?

Human connective tissue cells at 500x magnification (500 times larger than their real size)

Loeys-Dietz syndrome (LDS) is a genetic disorder that affects the body’s connective tissue.

What is Connective Tissue?

Connective tissue serves to connect, support, and help bind other tissues in the body.

Different types of connective tissue include fat-storing (adipose) cells, bone cells, red and white blood cells, as well as the loose meshwork of cells and fibers underlying skin layers. Elements of connective tissue are found throughout all organs of the body. 

Collagen and elastin are two proteins that make up connective tissue. Collagen is the main structural component of connective tissue and is found in blood vessels, bone, cartilage, cornea, skin, ligaments, and tendons. Elastin is a flexible protein that helps connective tissue to stretch and recoil and is found in ligaments, skin, and arteries.

There are two categories of connective tissue, loose connective tissue and dense connective tissue. Loose connective tissue is found in most organs and is rich in proteoglycans (proteins with long sugar side chains), but lower in collagen fibers. Dense connective tissue is found in artery walls, skin layers, tendons, and bones and includes more collagen fibers than loose connective tissue.

Connective Tissue Disorders

A connective tissue disorder affects the body’s connective tissue.

More than 200 disorders have been identified and causality and symptoms vary according to the different disorders.

Examples of connective tissue disorders that may affect the aorta are:

  • Loeys-Dietz syndrome (LDS)
  • Marfan syndrome (MFS)
  • Vascular Ehlers-Danlos syndrome (vEDS)
  • Shprintzen-Goldberg syndrome (SGS)
  • Meester-Loeys syndrome (MRLS)

Other connective tissue disorders include autoimmune disorders (when the immune system attacks healthy parts of the body) such as dermatomyositis, rheumatoid arthritis, scleroderma, Sjögren’s syndrome, systemic lupus erythematosus, and vasculitis.

Loeys-Dietz Syndrome and Similar Conditions

Marfan Syndrome vs. Loeys-Dietz Syndrome

Marfan syndrome (MFS) is caused by a mutation (change) in the fibrillin-1 (FBN1) gene, which is responsible for the strength and flexibility of connective tissue. On the other hand, Loeys-Dietz syndrome (LDS) is caused by a mutation in the SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, or TGFBR2 genes. These genes play a role in the TGF beta pathway, a series of molecular actions and interactions involved in the body’s development, growth, immune function, and tissue maintenance.


Distinguishing (unique) features of MFS include dolichostenomelia (prominently long limbs) and ectopia lentis (dislocation of the lens of the eye). However, some studies have reported ectopia lentis in LDS patients. 


Distinguishing manifestations of LDS include hypertelorism (widely-spaced eyes), arterial aneurysms that are widespread (found in the aorta and other arteries), arterial tortuosity (lengthened and twisted arteries), cleft palate (opening/gap in the roof of the mouth), and bifid (split) or broad uvula. Individuals with LDS are also more likely than those with MFS to have a translucent quality to their skin, abnormal scarring, hernias, poor wound healing, cervical spine instability, craniosynostosis (early joining of a baby’s skull), joint contractures and birth defects such as clubfoot and heart defects. LDS also has a greater incidence of pregnancy-related complications and aneurysms are more likely to dissect (burst) at a smaller size and younger patient age than in MFS. 


Individuals with LDS and MFS may share features such as aortic aneurysm and dissection, scoliosis, anterior chest deformity, pes planus (flat foot), dural ectasia (widening of dural sac), and spontaneous pneumothorax (collapsed lung).

Vascular Ehlers-Danlos Syndrome vs. Loeys-Dietz Syndrome

Vascular Ehlers-Danlos syndrome (vEDS) is caused by a mutation in the COL3A1 gene, which is responsible for collagen production. Individuals who exhibit vEDS-like symptoms but have a negative test result should be evaluated for Loeys-Dietz syndrome (LDS)


LDS patients may exhibit hypertelorism (widely-spaced eyes) and bifid (split) or broad uvula, unlike patients with vEDS.


LDS and vEDS both include skin-related findings such as easy bruising, soft or velvety skin texture, wide scarring, and translucent skin. Other shared features include clubfoot, joint hypermobility, a relatively high incidence of arterial aneurysms and some cases of sudden organ rupture. 

Shprintzen-Goldberg Syndrome vs. Loeys-Dietz Syndrome

Shprintzen-Goldberg syndrome (SGS) is caused by a mutation in the SKI gene, which is responsible for controlling the activity of the TGF beta pathway. 


Most individuals with SGS do not show a progressive or severe aneurysm formation and are more likely to show developmental delay than individuals with Loeys-Dietz syndrome (LDS).


Individuals with LDS and SGS may have similar features such as craniosynostosis (early joining of a baby’s skull), pectus anomalies, and scoliosis. 

Meester-Loeys Syndrome vs. Loeys-Dietz Syndrome

Meester-Loeys syndrome (MRLS) or BGN-Associated Aortic Aneurysm syndrome is caused by a mutation in the BGN gene, which is responsible for producing a protein (biglycan) that forms part of the skin and other connective tissues. 


Individuals with MRLS may exhibit ventricular dilation, large head circumference, excessive hair growth, gum enlargement, and lower collagen content, unlike people with Loeys-Dietz syndrome (LDS).


Shared manifestations of MRLS and LDS include hypertelorism (widely-spaced eyes), bifid (split) uvula, chest deformities, joint hypermobility, and early-onset aortic root dilation and dissection. 

Differential Diagnosis

LDS is a distinct disorder.

LDS was first described in 2005. At the time, medical professionals and researchers realized that while LDS shares some features with other connective tissue disorders, it is a distinct disorder as there are a variety of manifestations that set LDS apart.

Today, when medical professionals meet patients with connective tissue disorders, they may use a process called a differential diagnosis to compare conditions with similar features and determine which one is producing their patient’s symptoms.

The final identification of a patient’s condition based on their signs, symptoms, and laboratory findings is known as a clinical diagnosis.


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