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GENETICS IN NEUROLOGY

JAMA. 1967;199(4):270. doi:10.1001/jama.1967.03120040080016.
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The heredodegenerative diseases of the nervous system remain a confusing group of disorders, lacking an adequate system of classification. The rarity of many forms makes comprehensive study difficult. Overlapping clinical features in some families with disorders such as Charcot-Marie-Tooth disease, spastic paraplegia, and hereditary ataxia have produced additional confusion and have led to the frequent suggestion that such disorders fall on a continuum and are the result of a single genetic defect. Unfortunately, no laboratory methods are available to detect heterogeneity in families clinically and genetically indistinguishable.

However, genetic analysis can make useful nosological contributions in certain clinically homogeneous disorders. No unitary biochemical defect has been found with more than one mode of inheritance. Therefore, clinically indistinguishable families with alternate modes of inheritance must ipso facto be heterogeneous in pathogenesis. For example, there must be at least three types of spastic paraplegia, Charcot-Marie-Tooth disease, and muscular dystrophy, since each may

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