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In particular, it is reported that cEDS patients may show delayed motor development with mild hypotonia, characteristic facial features, fatigue and muscle cramps, premature rupture of fetal membranes, cervical insufficiency during pregnancy, rectal prolapse in early childhood, mild scoliosis, and cardiac/blood vessel fragility including mitral/tricuspid valve prolapse, and aortic root dilatation

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[122] In 1890, James Buchanan Duke founded the American Tobacco Company (ATC) and put the machines into mass-productions, which led to a decline in chewing tobacco and pipe smoking use in the United States

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