Loeys-Dietz syndrome

Loeys–Dietz syndrome (LDS) is a rare, inherited genetic disorder that affects the body’s connective tissue. It is caused by mutations in certain genes and can lead to problems in the blood vessels, skeleton, skin, and other organs. It is a related disorder to Marfan syndrome.

What is Loeys-Dietz?

Loeys-Dietz syndrome (LDS) is a congenital and hereditary disorder of the connective tissue. In some respects it resembles Marfan syndrome, but there are also important differences. The word “syndrome” indicates that it is a collection of symptoms that occur together and specifically in this combination. All of these symptoms can be explained by a single underlying cause.
This genetic condition is caused by mutations (errors) the TGF-β signaling pathway. So far, six different genes have been identified in which various DNA mutations can occur that may cause LDS.

Discovery

Loeys–Dietz syndrome (LDS) was first identified in 2005 by geneticists prof. dr. Bart Loeys from Belgium and prof. dr. Hal (Harry) Dietz from the USA at Johns Hopkins University. They discovered that certain patients who were previously thought to have Marfan syndrome actually had a different genetic condition caused by mutations affecting the TGF-β signaling pathway.

Their research led to the recognition of LDS as a distinct connective tissue disorder with its own genetic causes and clinical features.

Prevalence / types

Relatively little is known about the prevalence of Loeys–Dietz syndrome (LDS). Prof. dr. Bart Loeys has indicated that LDS can be considered about 10 times rarer than Marfan syndrome. If the prevalence of Marfan syndrome is estimated at 1 in 5,000, the prevalence of LDS would be approximately 1 in 50,000.

So far, six different gene mutations associated with Loeys–Dietz syndrome have been identified. These involve the following genes and corresponding LDS types:

  • TGFBR1 (LDS1)
  • TGFBR2 (LDS2)
  • SMAD3 (LDS3)
  • TGFB2 (LDS4)
  • TGFB3 (LDS5)
  • SMAD2 (LDS6)

The symptoms often vary depending on the specific type of LDS.

Symptoms

Four key features strongly point toward a diagnosis of Loeys-Dietz syndrome (LDS). These characteristics are rarely found together in other connective tissue disorders. They include:

Aneurysms

Aneurysms (widening or dilation of arteries), typically detected through imaging techniques. These most commonly occur at the aortic root (the base of the main artery leaving the heart), but they can also develop in arteries throughout the body.

Arterial toruosity

Arterial tortuosity (twisted or spiral-shaped arteries), most often seen in the vessels of the neck and identified imaging.

Hypertelorism

Hypertelorism, meaning the eyes are set wider apart than usual.

Bifid / broad uvula

Bifid (split) or broad uvula, referring to the small piece of tissue hanging at the back of the throat.

LDS can present in many different ways, and no two individuals will have exactly the same set of symptoms. If you have concerns about specific health issues, it is important to consult a physician or a clinical geneticist.

Below is a more detailed overview of other symptoms reported in individuals diagnosed with Loeys-Dietz syndrome, organized by body system.

Craniofacial (head and face)

  • Malar hypoplasia (flat cheek bones)
  • Slight downward slant to the eyes
  • Craniosynostosis (early fusion of the skull bones)
  • Cleft palate (hole in the roof of the mouth)
  • Blue sclerae (blue tinge to the whites of the eyes)
  • Micrognathia (small chin) and/or retrognathia (receding chin)

Skeletal

  • Long fingers and toes
  • Contractures of the fingers
  • Clubfoot or skewfoot deformity
  • Scoliosis (s-like curvature of the spine)
  • Cervical-spine instability (instability in the vertebrae directly below the skull)
  • Pectus excavatum (chest wall deformity that causes the sternum and breast bone to grow inward) / Pectus carinatum (chest wall deformity that pushes the sternum and breast bone out)
  • Joint laxity
  • Osteoarthritis
  • Typically normal stature

Skin

  • Translucent skin
  • Soft or velvety skin
  • Easy bruising
  • Abnormal or wide scarring
  • Soft skin texture
  • Hernias

Cardiac

  • Congenital (existing at birth) heart defects, which can include patent ductus arteriosus (PDA), atrial or ventricular septal defect (ASD/VSD) and bicuspid aortic valve (BAV)

Ocular

  • Myopia (nearsighted)
  • Eye muscle disorders
  • Retinal detachment: The retina is the light-sensitive layer of tissue that lines the inside of the eye and sends visual messages through the optic nerve to the brain. When the retina detaches, it is lifted or pulled from its normal position. If not promptly treated, retinal detachment can cause permanent vision loss.

OTHER

  • Food or environmental allergies
  • Gastrointestinal inflammatory disease
  • Hollow organs such as intestine, uterus and spleen prone to rupture