Meester-Loeys Syndrome

A number sign (#) is used with this entry because of evidence that Meester-Loeys syndrome (MRLS) is caused by mutation in the BGN gene (301870) on chromosome Xq28.

Clinical Features

Meester et al. (2017) studied 5 families in which affected males had early-onset aortic aneurysm and dissection, with the earliest occurrences at age 1 year and 15 years, respectively. The aneurysms involved the aortic root or more distal ascending aorta in all families. There was mild mitral or aortic insufficiency in some families. Cardiovascular phenotypes of carrier females ranged from unaffected to fatal aortic dissection. Affected individuals exhibited facial dysmorphism, including hypertelorism, proptosis, downslanting palpebral fissures, frontal bossing, and malar hypoplasia. Nonspecific connective tissue features included pectus deformities, joint hypermobility or contractures, and skin striae, as well as features of Loeys-Dietz syndrome (LDS; see 609192) such as bifid uvula and cervical spine instability. Other unusual features not typically seen in LDS or in Marfan syndrome (MFS; 154700) that were inconsistently observed in these patients included ventricular dilation on brain imaging, relative macrocephaly, hypertrichosis, and gingival hypertrophy, as well as evidence of skeletal dysplasia, including hip dislocation, platyspondyly, phalangeal dysplasia, and dysplastic epiphyses of the long bones. Meester et al. (2017) noted that histologic staining of aortic wall tissue from 2 of the probands showed low to normal collagen content and normal-appearing elastin fibers, in contrast to the increase in collagen content and fragmentation of elastic fibers that is typically observed in MFS and LDS.

Molecular Genetics

Meester et al. (2017) analyzed 368 extracellular matrix-related and TGFB (190180)-related genes in a cohort of 11 probands with molecularly unexplained MFS and identified 2 probands with mutations in the BGN gene (301870.0003 and 301870.0004). By sequencing BGN in 715 probands with thoracic aneurysm (see AAT1, 607086) who were negative for mutation in known AAT-associated genes, they identified 3 more probands with BGN mutations (see, e.g., 301870.0005 and 301870.0006). All of the mutations caused partial or total loss of function and segregated with disease in the 3 families for which DNA of other family members was available. Meester et al. (2017) concluded that BGN gene defects in humans cause a syndromic form of severe thoracic aortic aneurysm and dissection, the clinical features of which overlap with those of LDS and MFS patients.