Loeys-Dietz Syndrome Explained

Loeys-Dietz syndrome is a genetic disorder of the body’s connective tissue. It has some features in common with Marfan syndrome, but it also has some important differences.

People with Loeys-Dietz syndrome features need to see a doctor who knows about the condition to decide if they have the disorder; often this will be a medical geneticist.

It is very important that people with Loeys-Dietz syndrome get an early and correct diagnosis so they can get the right treatment.

What causes Loeys-Dietz syndrome?

Loeys-Dietz syndrome is caused by a genetic mutation of either one of the two genes that tell the body how to make proteins, including the proteins in connective tissue.

These genes are called transforming growth factor beta-receptor 1 (TGFβR1) and transforming growth factor beta-receptor 2 (TGFβR2).

When either of these genes has a mutation, growth and development of the body’s connective tissue and other body systems is disrupted, leading to the signs and symptoms of Loeys-Dietz syndrome.

What are the key features of Loeys-Dietz syndrome?

Because connective tissue is found throughout the body, Loeys-Dietz syndrome features can occur throughout the body, too, including the heart, blood vessels, bones, joints, skin, and internal organs such as the intestines, spleen, and uterus.

One of the key features of Loeys-Dietz syndrome is an enlargement of the aorta, the large blood vessel that carries blood from the heart to the rest of the body.

The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection).

This is a life-threatening complication that can occur without warning. In Loeys-Dietz syndrome, aneurysms and dissections also can occur in arteries other than the aorta.


Typ­i­cal signs and symp­toms of Loeys-Di­etz syn­drome may in­clude:

  • Aor­tic and ar­te­r­i­al tor­tu­os­i­ty (spi­raled or twist­ed ar­ter­ies)
  • En­larged or bulging aor­ta (aor­tic aneurysm), which may evolve to aor­tic rup­ture or dis­sec­tion (a tear in the ves­sel wall)
  • Aneurysms in ar­ter­ies oth­er than the aor­ta
  • Risk of blood clots at the site of the aneurysm
  • Preg­nan­cy-re­lat­ed com­pli­ca­tions in­clud­ing death and uter­ine rup­ture
  • Skele­tal ab­nor­mal­i­ties such as pre­ma­ture fu­sion of skull bones (cran­iosyn­os­to­sis), a curved spine (sco­l­io­sis), chest mal­for­ma­tions, an in­ward- and up­ward-turn­ing foot (club­foot), elon­gat­ed limbs with joint de­fects that re­strict move­ment, and poor min­er­al­iza­tion of the bones (os­teo­poro­sis), mak­ing the bones weak­er
  • Easy bruis­ing and ab­nor­mal or wide scar­ring
  • Joint pain (os­teoarthri­tis)
  • Wide­ly spaced eyes
  • A bi­fid uvu­la (a piece of con­nec­tive tis­sue that hangs from the back of the mouth and plays a role in ar­tic­u­la­tion)
  • A cleft palate (an open­ing in the palate)
  • Skin ab­nor­mal­i­ties; the skin may be­come translu­cent, leav­ing the un­der­ly­ing veins vis­i­ble

De­pend­ing on the type of Loeys-Di­etz syn­drome, some symp­toms may be ab­sent or vary in sever­i­ty.

In cas­es where an aor­tic dis­sec­tion or rup­ture oc­curs, typ­i­cal signs are a sud­den, se­vere chest pain, a short­ness of breath, sud­den dif­fi­cul­ty speak­ing, re­duced vi­sion, and loss of con­scious­ness.

Rup­tures will pro­duce life-threat­en­ing in­ter­nal bleed­ing and re­quire im­me­di­ate med­ical in­ter­ven­tion.


Most tho­racic aneurysms are asymp­tomatic and are typ­i­cal­ly de­tect­ed when the chest is im­aged for un­re­lat­ed rea­sons (typ­i­cal­ly via chest x-rays, CT (com­put­er­ized to­mog­ra­phy) scans, MRI (mag­net­ic res­o­nance imag­ing), echocar­dio­gram, etc.).

Cur­rent­ly, a di­ag­no­sis of Loeys-Di­etz syn­drome is usu­al­ly based on fam­i­ly his­to­ry and the pres­ence of typ­i­cal phys­i­cal fea­tures.

If there is sus­pi­cion of Loeys-Di­etz syn­drome, imag­ing is per­formed to iden­ti­fy and eval­u­ate any aor­tic aneurysms.

A ge­net­ic test can iden­ti­fy the ex­act un­der­ly­ing ge­net­ic de­fect, which can pro­vide con­fir­ma­tion of the di­ag­no­sis and pre­dic­tion of clin­i­cal out­comes.

Since the aneurysms tend to rup­ture when pa­tients with Loeys-Di­etz syn­drome are young, ear­ly and ac­cu­rate di­ag­no­sis is cru­cial.


Sur­gi­cal and clin­i­cal meth­ods for man­age­ment of the com­pli­ca­tions of Loeys-Di­etz syn­drome are are rapid­ly be­ing de­vel­oped.

Cur­rent­ly, man­age­ment of aneurysms is fo­cused on pre­ven­tion and con­sists of reg­u­lar­ly mon­i­tor­ing the size of the aneurysm, con­trol­ling blood pres­sure, and treat­ing any car­dio­vas­cu­lar risk fac­tors.

Reg­u­lar fol­low-ups are used to fol­low the pro­gres­sion of any aor­tic di­la­tions, typ­i­cal­ly us­ing imag­ing tech­niques like CT or MRI scans.

Sur­gi­cal re­pair of the aneurysm be­fore a rup­ture or dis­sec­tion presents is gen­er­al­ly suc­cess­ful and can great­ly en­hance the pa­tient’s out­come.

Pa­tients can al­so ben­e­fit from treat­ments that low­er the heart rate and blood pres­sure, such as be­ta-block­ers, an­giotensin II re­cep­tor block­ers (an­giotensin II nar­rows your blood ves­sels), or cho­les­terol-low­er­ing drugs.

These re­lieve the pres­sure the blood flow places on the aor­tic wall.

Skele­tal com­pli­ca­tions may re­quire treat­ment through or­tho­pe­dic surgery or oth­er in­ter­ven­tions such as brac­ing or har­ness­es.

Pre­lim­i­nary ex­per­i­ments in mouse mod­els have shown promis­ing re­sults for med­ica­tion that an­tag­o­nizes TGF ß, the growth fac­tor that is cen­tral to the patho­gen­e­sis of Loeys-Di­etz syn­drome.

How­ev­er, this ap­proach still re­quires val­i­da­tion in ad­di­tion­al an­i­mal mod­els and clin­i­cal tri­als.


The mean life ex­pectan­cy of pa­tients with Loeys–Di­etz syn­drome is 37 years, which is quite low com­pared to re­lat­ed con­nec­tive tis­sue dis­or­ders.

The re­duced life ex­pectan­cy is due to the fact that aor­tic dis­sec­tions oc­cur at small­er di­am­e­ters (from 40 mm) and at a younger age (26.7 years) in Loeys-Di­etz syn­drome pa­tients.

It is ex­pect­ed that the out­look for af­fect­ed in­di­vid­u­als will con­tin­ue to im­prove as more is learned about the dis­or­der and a di­ag­no­sis can be made at an ear­li­er age.

When an aor­tic aneurysm is de­tect­ed ear­ly and treat­ed prompt­ly, the chance of sur­vival great­ly im­proves.

Iden­ti­fi­ca­tion of the ex­act ge­net­ic de­fect can dis­tin­guish be­tween Loeys–Di­etz and re­lat­ed con­di­tions, and en­ables in­di­vid­u­al­ized coun­sel­ing and pre­ven­tive dis­ease man­age­ment.

Source & More Info: marfan.org and results.gentlelabs.com



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