Alternative titles; symbols
ORPHA: 99715;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q21.1 | MASS syndrome | 604308 | Autosomal dominant | 3 | FBN1 | 134797 |
A number sign (#) is used with this entry because of evidence that MASS syndrome is caused by heterozygous mutation in the gene encoding fibrillin (FBN1; 134797) on chromosome 15q21.
Glesby and Pyeritz (1989) pointed out that more than half of a large number of patients evaluated in the medical genetics clinic at Johns Hopkins for a possible heritable disorder of connective tissue could not be precisely classified. As a group, these patients showed many manifestations of the Marfan syndrome (MFS; 154700), including long limbs, deformity of the thoracic cage, striae atrophicae, mitral valve prolapse, and mild dilatation of the aortic root. Clinical clustering did not emerge when patients were stratified by mitral valve prolapse or aortic dilatation. The clinical phenotype of patients with mitral valve prolapse constituted a continuum, from Marfan syndrome at one extreme to isolated mitral valve prolapse due to myxomatous change of the valve leaflets (see 157700). In the absence of biochemical or DNA markers, the diagnosis of Marfan syndrome was impossible when a patient had mitral valve prolapse and mild aortic root dilatation but no ectopia lentis or family history of definite Marfan syndrome. Glesby and Pyeritz (1989) suggested that until subclassification based on genetic and biochemical indicators is possible, these patients should be considered as having an overlap heritable connective disorder. They further suggested the acronym 'MASS phenotype' to designate the involvement of the mitral valve, aorta, skeleton, and skin.
By applying the revised Ghent criteria (Loeys et al., 2010) to an established adult population of 180 patients diagnosed with Marfan syndrome, Radonic et al. (2011) diagnosed 4 with MASS syndrome. All 4 patients had a normal Z-score and an aortic root diameter of less than 2. Clinical features included wrist and thumb sign, hindfoot deformity, reduced upper segment/lower segment ratio and increased arm span/height ratio, pectus carinatum, mitral valve prolapse, dural ectasia, scoliosis, and striae. None of the patients had ectopia lentis.
Radonic et al. (2011) applied the revised Ghent criteria to an established adult population of 180 patients diagnosed with Marfan syndrome. In 164 patients (91%), the diagnosis held. Of the 16 patients in whom the diagnosis was rejected, 4 were diagnosed with MASS phenotype and 3 with ectopia lentis syndrome; in 9, no alternative diagnosis was established. The MFS diagnosis was rejected in 13 patients, including the 4 with MASS phenotype, because the aortic root Z-score was less than 2, and in 3 patients because less weight was given to dural ectasia.
Dietz et al. (1993) demonstrated that one basis for the MASS phenotype is a nonsense frameshift mutation in the FBN1 gene (134797.0012).
Dietz, H. C., McIntosh, I., Sakai, L. Y., Corson, G. M., Chalberg, S. C., Pyeritz, R. E., Francomano, C. A. Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome. Genomics 17: 468-475, 1993. [PubMed: 8406497] [Full Text: https://doi.org/10.1006/geno.1993.1349]
Glesby, M. J., Pyeritz, R. E. Association of mitral valve prolapse and systemic abnormalities of connective tissue: a phenotypic continuum. JAMA 262: 523-528, 1989. [PubMed: 2739055]
Loeys, B. L., Dietz, H. C., Braverman, A. C., Callewaert, B. L., De Backer, J., Devereux, R. B., Hilhorst-Hofstee, Y., Jondeau, G., Faivre, L., Milewicz, D. M., Pyeritz, R. E., Sponseller, P. D., Wordsworth, P., De Paepe, A. M. The revised Ghent nosology for the Marfan syndrome. J. Med. Genet. 47: 476-485, 2010. [PubMed: 20591885] [Full Text: https://doi.org/10.1136/jmg.2009.072785]
Radonic, T., de Witte, P., Groenink, M., de Bruin-Bon, R. A. C. M., Timmermans, J., Scholte, A. J. H., van den Berg, M. P., Baars, M. J. H., van Tintelen, J. P., Kempers, M., Zwinderman, A. H., Mulder, B. J. M. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome. Clin. Genet. 80: 346-353, 2011. [PubMed: 21332468] [Full Text: https://doi.org/10.1111/j.1399-0004.2011.01646.x]