ABSTRACT
The clinical practice of neurogenetics is complex, challenging, and rewarding. Several guidelines will be helpful. This chapter will briefly focus on eight aspects of clinical neurogenetics, namely, (i) Factors suggesting the presence of a genetic disease, (ii) Neurogenetic diseases that may be ‘‘hiding’’ in nonspecific categories, (iii) The importance of family history, (iv) The assessment of sporadic cases, (v) Genetic counseling, (vi) Genetic testing, (vii) Available information resources, and (viii) An integrated clinical neurogenetic strategy. [A discussion of this approach has appeared previously in Ref. (1).]
FACTORS SUGGESTING A NEUROGENETIC DISORDER
Table 1 highlights several of the clues indicating an increased probability that a patient may have a neurogenetic disorder. First and foremost is the presence of a positive family history. By nature, genetic diseases are usually inherited (although there are exceptions), and thus it is common to identify other affected family members. This is true of all patterns of inheritance including autosomal dominant, autosomal recessive, X-linked, and mitochondrial. Therefore, a positive family history of at least two similarly affected individuals is a compelling sign of a genetic disorder. However, there are two major exceptions to finding a positive family history. The first is that isolated or sporadic cases without a positive family history can still be genetic. The various explanations for sporadic cases are discussed later in
this chapter. The second exception is that not all familial disorders are genetic. In other words, family members sharing the same environment may be affected with the same nongenetic acquired disease. For example, common exposure to infectious or toxic agents may produce a positive family history of a disorder (such as neuropathy or ataxia), which is not genetic. Thus, although a positive family history is a strong sign of a genetic disease, all familial disorders are not always genetic and all genetic disorders are not always familial.
