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The hallmark of all the hereditary metabolic diseases is psychosensorimotor regression However, those that have their onset in the rst year of life pose extraordinary problems in neurologic diagnosis If the onset is in the rst postnatal months, before the infant has had time to develop the normal complex repertoire of behavior, the rst signs of disease may take the form of subtle delays in maturation rather than of psychomotor regression Departures from normalcy include a lack of interest in the surroundings, a lack of visual engagement, poor head control, an inability to sit up at the usual time, poor hand-eye coordination, and persistence of infantile automatisms.

whom one of each pair is known to have MS In the most extensive of these studies (Ebers et al), the diagnosis was veri ed in 12 of 35 pairs of monozygotic twins (34 percent) and in only 2 of 49 pairs of dizygotic twins (4 percent) Furthermore, in two additional sets of monozygotic twins who were clinically normal, lesions were detected by MRI The concordance rate in dizygotic pairs is similar to that in nontwin siblings Despite these provocative ndings, no consistent pattern of mendelian inheritance has emerged (Of course, one must not assume that all diseases with an increased familial incidence are hereditary in that instances of the same condition in several members of a family may simply re ect an exposure to a common environmental agent Paralytic poliomyelitis, for example, was about eight times more common in immediate family members than in the population at large.

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Once again, calling a subroutine starts with the subroutine s name (here, Power), followed by its argument in parentheses (here, one argument because this subroutine was declared as having one parameter). If you ran the program in debug mode and clicked the form, the value 25 would be displayed in the Output window. The statement Power(5) has the effect of assigning the value 5 to the parameter num in Power. Therefore, the statement in Power

) Nonetheless, further evidence of a genetic factor in the causation of MS is the nding that certain histocompatibility locus antigens (HLAs) are more frequent in patients with MS than in control subjects The strongest association is with the DR locus on the sixth chromosome Other HLA haplotypes that are overrepresented in MS (HLA-DR2 and, to a lesser extent, -DR3, -B7, and -A3) are thought to be markers for an MS susceptibility gene possibly an immune response gene The presence of one of these markers increases the risk that an individual will develop MS by a factor of 3 to 5 These antigens may indeed prove to be related to the frequency of the disease, but their presence is not invariable and their exact role is far from clear (see Compston).

The low conjugal incidence of MS, on the other hand, indicates that any common exposure to an inciting infection or environmental agent must occur early in life In order to test this hypothesis, Schapira and coworkers determined the periods of common exposure (common habitation periods) in members of families with two or more cases From this they calculated the mean common exposure to have happened before 14 years of age, with a latency of about 21 years gures that are in general agreement with those derived from the migration studies quoted above The incidence of MS is two or three times higher in women than in men, but the signi cance of this fact is unclear, the best current explanation being that women are generally more susceptible to immune and in ammatory conditions The incidence in children is very low; only 03 to 0.

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4 percent of all cases appear during the rst decade In an analysis of three childhood-onset cases, Hauser and colleagues found no phenotypic differences between childhood and adult cases Beyond childhood, the risk of rst developing symptoms of the disease rises steeply with age, reaching a peak at about 30 years, remaining high in the fourth decade, then falling off sharply and becoming low in the sixth decade It has been pointed out that MS has a unimodal age-speci c onset curve, similar to the age-speci c onset curves of many infectious and connective tissue diseases About two-thirds of cases of MS have their onset between 20 and 40 years of age Of the remainder, most cases begin before the age of 20; in a smaller number, the disease appears to develop in late adult life (late fties and sixties).

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