More than half of all patients evaluated in our clinic for the possible diagnosis of a heritable disorder of connective tissue could not be classified in the current nosology, yet they had considerable clinical evidence of a systemic defect of the extracellular matrix. As a group, these patients share many manifestations of the Marfan syndrome 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 constitutes a continuum, from Marfan syndrome at one extreme to isolated mitral valve prolapse due to myxomatous proliferation of the valve leaflets. In the absence of biochemical or DNA markers, discerning whether a patient with mitral valve prolapse and mild aortic root dilatation (in the absence of ectopia lentis or a family history) has Marfan syndrome, or another heritable disorder of connective tissue, will continue to be a clinical challenge. Until subclassification based on refined clinical, genetic, and laboratory investigations is possible, the patients we describe are best seen as having an "overlap" heritable connective-tissue disorder. We suggest the acronym "MASS phenotype" to emphasize involvement of the mitral valve, aorta, skeleton, and skin.