Question: What is (are) Loeys-Dietz syndrome ?
Answer: Loeys-Dietz syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, and blood vessels. There are four types of Loeys-Dietz syndrome, labelled types I through IV, which are distinguished by their genetic cause. Regardless of the type, signs and symptoms of Loeys-Dietz syndrome can become apparent anytime in childhood or adulthood, and the severity is variable. Loeys-Dietz syndrome is characterized by enlargement of the aorta, which is the large blood vessel that distributes 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). People with Loeys-Dietz syndrome can also have aneurysms or dissections in arteries throughout the body and have arteries with abnormal twists and turns (arterial tortuosity). Individuals with Loeys-Dietz syndrome often have skeletal problems including premature fusion of the skull bones (craniosynostosis), an abnormal side-to-side curvature of the spine (scoliosis), either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum), an inward- and upward-turning foot (clubfoot), flat feet (pes planus), or elongated limbs with joint deformities called contractures that restrict the movement of certain joints. Degeneration of the discs that separate the bones of the spine (vertebrae), often affecting the neck, is a common finding. Some affected individuals have prominent joint inflammation (osteoarthritis) that commonly affects the knees and the joints of the hands, wrists, and spine. People with Loeys-Dietz syndrome may bruise easily and develop abnormal scars after wound healing. The skin is frequently described as translucent, often with stretch marks (striae) and visible underlying veins. Other characteristic features include widely spaced eyes (hypertelorism), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and an opening in the roof of the mouth (cleft palate). Individuals with Loeys-Dietz syndrome frequently develop immune system-related problems such as food allergies, asthma, or inflammatory disorders such as eczema or inflammatory bowel disease.
Source: GHR

Question: What are the genetic changes related to Loeys-Dietz syndrome ?
Answer: The four types of Loeys-Dietz syndrome are distinguished by their genetic cause: mutations in the TGFBR1 gene cause type I, mutations in the TGFBR2 gene cause type II, mutations in the SMAD3 gene cause type III, and mutations in the TGFB2 gene cause type IV. These four genes play a role in cell signaling that promotes growth and development of the body's tissues. This signaling pathway also helps with bone and blood vessel development and plays a part in the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells. Mutations in the TGFBR1, TGFBR2, TGFB2, and SMAD3 genes result in the production of proteins with little or no function. Even though these proteins have severely reduced function, cell signaling occurs at an even greater intensity than normal. Researchers speculate that the activity of proteins in this signaling pathway is increased to compensate for the protein whose function is reduced; however, the exact mechanism responsible for the increase in signaling is unclear. The overactive signaling pathway disrupts the development of connective tissue, the extracellular matrix, and various body systems, leading to the varied signs and symptoms of Loeys-Dietz syndrome.
Source: GHR