Supposition: Navigators are descended from Jihad-era human stock which was probably fairly normal other than exhibiting an aptitude for higher mathematics and prescient abilities.
The question then is what are the sources of the physical deformities described for Navigators?
Because they come along relatively late in the game, when presumably the shielding on ships and orbital or deep space stations has reached a high level of development, I think we'd be pretty safe in ruling out higher exposure to cosmic radiation as a possible source. (Acceptable assumption?)
That leaves as sources:
(1) Normal (random) genetic mutations under conditions of non-natural, non-Darwinian selection, accumulating over a period of ten millennia.
(2) Aberrant ontogenesis due to low-gravity environments. (Non-genetic so not passed on, specific to individuals, but likely paralleled by many)
(3) Genetic mutations resulting from excessive ingestion of melange spice and overexposure to melange gas, in generations following the introduction of the spice to enhance prescience. I assume such mutations would be expressed as changes in the body of the individual in the same way as a cancer might be. (Acceptable?)
It is unclear whether Navigators can mate and produce viable offspring after they enter their final stages of (spice-induced) development. But even if they can, it is not certain that the mutations caused by the spice would be transmitted to offspring in the same way they manifest in the father. (Only mutations in germline/reproductive cells would be passed on.)
So ... that gives us heredity and growth environment and level of spice exposure as the determinants of an individual Navigator's ultimate physical form (with a possibility of some influence of the spice on heredity and the form of the next generation).
(How's this for a start?
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