This is an inherited condition of the connective tissues which are responsible for connecting different structures of the body. The syndrome affects the skin, heart, bones, blood vessels and other organs. There are five types of Loeys-Dietz syndrome that are based on their genetic cause. The severity of this condition is variable and can occur among individuals anytime from childhood through adulthood.
Causes
Loeys-Dietz syndrome develops as the result of a genetic mutation. The five different types of this syndrome is characterized by their genetic cause: mutation in TGFBR1 causes type 1, TGFBR2 causes type II, SMAD3 causes type III, TGFB2 type IV and TGFB3 genetic mutation causes type V. All these genes are essential for the cell signaling pathway known as transforming growth factor beta pathway which is important for the normal process of growth and development. The genetic mutation of any one of these genes can affect the normal growth and development of the body’s connective tissue resulting in the symptoms associated with this condition.
Symptoms
As this is a disorder of the connective tissue, the features of this condition can develop throughout the body including the heart, skin, internal organs, bones, blood vessels and the joints. One of the features of Loeys-Dietz syndrome is the enlarged aorta; the large blood vessel responsible for the transportation of blood from the heart to other parts of the body. Among individuals with this condition, the aorta can weaken and stretch causing an aneurysm or aortic dissection which is a sudden tear of the aorta wall. Other features include congenital heart defects such as patent ductus arteriosus, atrial septal defect and arteries that twist (arterial tortuosity). They can also exhibit cleft palate, malformation or the instability of the spinal bones, widely spaced eyes (hypertelorism), club foot, osteoporosis, easy bruising and translucent skin. Additional features can include rupture of the spleen or the bowel, gastrointestinal problems such as difficulty with absorbing food and chronic diarrhea.
Diagnosis
As this is a recently identified disorder, a medical geneticist is most likely to recognize this condition. The diagnosis is based on the family history of the individual, a physical examination and identification of the features associated with this syndrome. Some of the diagnostic tests include imaging studies of the head, skeleton and the blood vessels. An echocardiogram, an angiogram or a CT scan may be necessary to detect the features. The molecular genetic testing can also help detect the mutation that is responsible for causing this condition.
Treatment
As the severity of this condition varies among the affected cases, the treatment also differs. The pressure on the aorta can be controlled with medications, rarely surgery for cervical spine fusion is required and an orthopedic surgery for foot deformities or hip dislocation. The vascular surgery is often recommended as a preventive method for the rapidly enlarging aorta or artery and those with a severe inflammatory disease of the intestines may require medications or feeding tubes. These affected individuals are also recommended to have continuous monitoring of the aorta with annual echocardiograms to detect and monitor the development of an aneurysm and dissections (tearing).
References
http://www.loeysdietz.org/en/medical-information/treatment-options
http://www.loeysdietz.org/images/LDS_Facts-1.pdf
https://www.marfan.org/resource/fact-sheet/loeys-dietz-syndrome#.WNunEdKGPIU
https://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome#genes
