For confirmation of symptoms and the clinical diagnosis related to Aortic aneurysm, familial thoracic 3 (AAT3); Loeys-Dietz syndrome, type 1B (LDS1B) TGFBR2; Marfan syndrome, type II (MFS2).
Aortic aneurysm, familial thoracic 3 (AAT3). AAT5 and AAT3 have been linked to mutations in the transforming growth factor Beta receptor type I and II genes (TGFBR1 and TGFBR2). Patients may have aneurysms of the aorta and other arteries. TGFBR2 mutations are currently estimated to be responsible for 5% of familial thoracic aortic aneurysms and dissections (TAAD).
Loeys-Dietz syndrome (LDS) is a recently described syndrome caused by mutations in one of two genes, TGFBR1 (Type 1A) or TGFBR2 (Type 1B). The reported phenotype is highly variable and overlaps considerably with Ehlers-Danlos syndrome IV or Marfan syndrome, type 2. A high percentage of patients have aortic root aneurysm or other arterial aneurysms. Some have cardiac abnormalities including patent ductus or atrial septal defects. Many display arterial tortuosity. Skeletal defects may include hypertelorism, pectus defects, joint laxity, craniosynostosis, arachnodactyly, scoliosis, talipes equinovarus, camptodactyly and malar hypoplasia. Some have dural ectasia. Additional features may include uterine, spleen or bowel rupture, thin, translucent, hyperextensible or velvety skin with atrophic scars and easy bruising. Blue sclera and a bifid uvula have also been observed.
Marfan syndrome, type I and type II are autosomal dominantly inherited disorders potentially affecting numerous organ sites. These include: the bones, eyes, lungs, skin, CNS and cardiovascular system. The most serious consequence of Marfan syndrome is due to the progressive dilatation of the aortic root and the consequent potential for dissection. MFS1 is caused by mutations in the FBN1 gene. This gene codes for fibrillin 1, a component of microfibrils. Microfibrils are found in both elastic and non-elastic tissues. Over 1000 different FBN1 mutations have been identified in Marfan syndrome, type I. Most mutations are single nucleotide substitutions or small insertions and deletions. Large FBN1 gene deletions are estimated to represent 2% of the mutations. MFS2 is caused by mutations in the gene coding for TGF-Beta receptor 2 (TGFBR2).
Published estimates of test sensitivity for genes linked to certain disorders can be very inaccurate, and that it is difficult to predict the probability of detecting a mutation in any single gene for one individual. The following factors contribute to this challenge: Many disorders have overlapping phenotypes; some disorders are linked to mutations in more than one gene; in some instances genes remain to be linked to specific disorders; for most disorders, proper diagnosis requires that clinical findings are considered along with genetic findings.