What are the other Names for this Condition? (Also known as/Synonyms)

• Aortic Aneurysm Syndrome, Loeys-Dietz type
• Furlong Syndrome
• Loeys-Dietz Aortic Aneurysm Syndrome

What is Loeys-Dietz Syndrome? (Definition/Background Information)

• Loeys-Dietz Syndrome is a connective tissue disorder that causes aortic aneurysms, widely spaced eyes (hypertelorism), cleft palate and/or split uvula (the little piece of flesh that hangs down in the back of the mouth) and twisting or spiraled arteries (arterial tortuosity)
• Other findings include craniosynostosis, extropia (eyes that turn outward), micrognathia, structural brain abnormalities, intellectual deficit, and congenital heart disease. Signs and symptoms vary among individuals. This condition is inherited in an autosomal dominant manner with variable clinical expression
• This condition is called Loeys-Dietz Syndrome type 1 when affected individuals have cleft palate, craniosynostosis, and/or hypertelorism. Individuals without these features are said to have Loeys-Dietz Syndrome type 2. The disease is caused by mutations in the TGFBR1, the TGFBR2, the SMAD3 or the TGFB2 genes
• It is important to have an early and adequate treatment for the heart problems because the chance for aortic dissection and other vascular problems may be high in some patients. Many specialists may be involved for the best management of the patient

(Source: Loeys-Dietz Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Loeys-Dietz Syndrome? (Age and Sex Distribution)

• Loeys-Dietz Syndrome is a rare congenital disorder, with an unknown prevalence 
• The presentation of symptoms may occur at birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Loeys-Dietz Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Loeys-Dietz Syndrome is an inherited condition
• Currently, no other risk factors have been clearly identified for the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Loeys-Dietz Syndrome? (Etiology)

Loeys-Dietz Syndrome may be caused by mutation(s) in several genes, and is classified into 5 types, on the basis of the gene involved:

• Loeys-Dietz Syndrome type I - caused by TGFBR1 gene mutations
• Loeys-Dietz Syndrome type II - TFFBR2 gene mutations cause this condition
• Loeys-Dietz Syndrome type III - caused by SMAD3 gene mutations
• Loeys-Dietz Syndrome type IV - caused by mutations in the TGFB2 gene
• Loeys-Dietz Syndrome type V - caused by mutations in the TGFB3 gene

In 75% of cases, the condition is not inherited, but develops as a de novo mutation in one of the causative genes. In cases that are classified as familial, the condition is inherited in an autosomal dominant manner.

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Loeys-Dietz Syndrome?

The signs and symptoms of Loeys-Dietz Syndrome may vary among affected individuals, and may include:

Very frequently present symptoms in 80-99% of the cases:

• Aortic aneurysm 
• Aortic dissection 
• Arterial dissection 
• Arterial tortuosity 
• High palate
• Patent ductus arteriosus 
• Pes planus
• Uterine rupture

Frequently present symptoms in 30-79% of the cases:

• Arachnodactyly
• Atypical scarring of skin
• Bifid uvula 
• Blue sclerae 
• Camptodactyly of finger 
• Craniosynostosis 
• Hypertelorism
• Malar flattening
• Micrognathia 
• Oral cleft
• Scoliosis 
• Striae distensae
• Tall stature

Occasionally present symptoms in 5-29% of the cases:

• Bruising susceptibility
• Cardiac arrest 
• Joint dislocation
• Joint hyperflexibility 
• Pectus carinatum
• Pectus excavatum
• Thin skin

(Source: Loeys-Dietz Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Loeys-Dietz Syndrome Diagnosed?

Loeys-Dietz Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm specific causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Loeys-Dietz Syndrome?

The complications of Loeys-Dietz Syndrome may include:

• Severe scarring after wound healing
• Osteoarthritis and resultant severe pain 
• Crowding or organs in the chest cavity due to scoliosis, leading to under-developed lungs and heart tissue
• Spontaneous pneumothorax (collapse of lungs)
• Abnormal heart function and risk of cardiac failure

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Loeys-Dietz Syndrome Treated?

There is no cure for Loeys-Dietz Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Loeys-Dietz Syndrome be Prevented?

Currently, Loeys-Dietz Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Loeys-Dietz Syndrome? (Outcomes/Resolutions)

• The prognosis of Loeys-Dietz Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Loeys-Dietz Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/