Loeys-Dietz Syndrome: What Is It And What is Known About Its Genetic Causes?

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What Is Loeys-Dietz Syndrome?

Loeys-Dietz Syndrome (LDS) is an inherited disorder that was first described in 2005 by Drs. Bart Loeys and Harry Dietz of Johns Hopkins School of Medicine. LDS affects connective tissue and causes its sufferers to experience one or more of several symptoms and growth and developmental defects, many of which are typically severe. These symptoms and defects include but are not limited to:

  • Craniofacial defects. Typical defects of this kind include, for example, widely spaced eyes (a condition known as hypertelorism), an abnormally broad or divided uvula (which is the small, fleshy piece of tissue that hangs in the back of the throat above the tongue), and cleft palate (a developmental defect that affects the upper lip and roof of the mouth)
  • Blood vessel abnormalities. Defects of this variety include, for example, blood vessels that are abnormally twisted and overly winding (this is especially seen in the blood vessels of the neck), enlarged blood vessels (particularly, the aorta), and blood vessels that are prone to tearing and aneurysm (rupture).
  • Skin problems. Commonly seen defects of this kind include, for example, abnormally soft skin, thin skin, skin that easily bleeds, and skin that is prone to scarring.

Less frequently seen abnormalities include food allergies, problems that affect the digestive system, clubfoot, flat feet, scoliosis and other spinal defects, and recurring migraine headaches.

The incidence of LDS in the world’s population is unknown. Further, it is not known whether LDS is more prevalent in any particular racial group or groups than any others. However, molecular geneticists are currently investigating these issues, so answers may come soon.

What Is Known About The Genetics of Loeys-Dietz Syndrome?

There are two genes that are known to be associated with LDS. These genes are designated TFGRB1 and TFGRB2 and they encode the proteins transforming growth factor-beta receptor 1 and transforming growth factor-beta receptor 2, respectively. These proteins are involved in a cellular process known as signal transduction, in which these proteins send signals within cells that are needed for proper growth and development.

LDS is an autosomal dominant genetic disorder, which means a person having one or more mutations in even only one of her two TFGRB1 or two TFGRB2 genes likely will suffer the symptoms and defects of LDS. Mutation of either of these genes will detrimentally affect the protein that they encode, which means that the protein will be suboptimal or entirely ineffective in its role in the cellular signal transduction process. Aberrations to that process affect the cell’s ability to participate in normal growth and development events, which causes these events to go awry in LDS sufferers and leads to the symptoms and defects described above.

A Final Word About Loeys-Dietz Syndrome

As mentioned, the symptoms and defects of LDS are numerous and many are severe. There is no simple, straightforward therapeutic option for adequately treating LDS patients. Instead, proper care of these patients is on-going and complex and involves the services of a diverse medical team of specialists, which is typically comprised of a cardiologist, orthopedist, cardiothoracic surgeon, medical geneticist, and genetic counselor, among any other professionals who may be necessary to treat a particular patient. It is hoped that further study of LDS and its genetics will enable the development of improved treatment options.


B.L. Loeys and H.C. Dietz, Loeys-Dietz Syndrome, Gene Reviews, University of Washington: https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=loeys-dietz

Genetics Home Reference, National Institutes of Health, TGFBR2: https://ghr.nlm.nih.gov/gene/TGFBR2

Johns Hopkins Medicine, Johns Hopkins Heart and Vascular Institute, L_oeys-Dietz Syndrome_: https://www.hopkinsmedicine.org/heart_vascular_institute/conditions_treatments/conditions/loeys_dietz.html

Loeys-Dietz Syndrome Foundation, Medical Information: https://www.loeysdietz.org/medical.php