Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Marfan Syndrome Type 2 (MFS2) [Q87.4]

OMIM numbers: 154705, 190181 (TGFBR1), 190182 (TGFBR2)

Dr. rer. nat. Karin Mayer, Dr. med. Imma Rost

Scientific Background

MFS2 originally described a phenotype which, similar to the classic Marfan syndrome, is characterized by skeletal abnormalities (macrosomia, arachnodactyly, pectus excavatum) and cardiovascular signs (mitral valve prolapse, dilated aortic root, aortic aneurysm); however, it does not display ocular manifestations, especially no lens luxation. The phenotype of MFS2 overlaps with the classic MFS and shares major similarities with the Loes-Dietz syndrome (LDS). Considering the clinical and molecular genetic definition of LDS in 2005, referring to MFS2 as its own entity has become questionable.

Already in 1993, a second gene location for the Marfan syndrome was localized on chromosome 3p25-p24.2 in a family displaying classical signs and symptoms of the MASS phenotype but no visual signs and symptoms; it was termed MFS2. In 2004, a translocation with the breaking point in 3p24.1 in the TGFBR2 gene was identified in another patient with MFS2. In 2004, a TGFBR2 mutation was also found in the MFS2 family described in 1993. So that for the first time, mutations in the TGFBR2 gene have been associated with MFS2. Just like LDS, MFS2 is caused by mutations in the TGFBR1 and TGFBR2 gene. Until now, mutations in TGFBR1 and TGFBR2 have been identified in 5-25% of all patients with Marfan-like signs and symptoms, MFS2 or incomplete Marfan signs and symptoms and no mutations in the FBN1 gene.