The causes of profound deafness in childhood : a study of 3,535 individuals with severe hearing loss present at birth or of childhood onset / George R. Fraser.

  • Fraser, George R. (George Robert)
Date:
[1976], ©1976
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Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: The causes of profound deafness in childhood : a study of 3,535 individuals with severe hearing loss present at birth or of childhood onset / George R. Fraser. Source: Wellcome Collection.

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    previous chapters are represented but are unidentifiable in the individual case. The optimal assignment of the cases in this group to etiological categories represents a statistical problem of some magnitude and Chapter XIV is largely concerned with an attempt to achieve this goal. The most striking conclusion which emerges from the attempt at a synthesis contained in Chapters XV and XVI concerns the pronounced heterogeneity of biological causation involving an entity which, from the educational, social, and even medical, point of view, is often regarded as relatively homogeneous. This is, of course, a common phenomenon in the fields of human biology and of human disease in general and is particularly pronounced in genetic nosology. Thus, each broad category of childhood handicap, whether it is deafness, mental subnormality, blindness, cerebral palsy, epilepsy, skeletal dystrophy, muscular dystrophy, or neurological defect, can be subdivided into a great number of entities and subentities, a substantial proportion of which are of simple genetic or Mendelian causation. In the field of deafness, this genetic subdivision cannot be carried very far because of the difficulty of accurate clinical investigation of the ear and because of our total ignorance of the underlying biochemical lesions. Thus, within the three main subgroups of autosomal recessive, autosomal dominant, and X-linked inheritance, only a few entities can be individually characterized on the basis of associated clinical features. Nevertheless, this will not always be the case, and it is to be expected that within the foreseeable future it will be possible to define each type of genetically determined deafness by other criteria, such as can be employed at present, for example, for defining galactosemia and phenylketonuria on biochemical grounds as two specific forms of mental subnormality. In such developments an important role will be played by those genetic syndromes which are defined at the clinical level. Thus, the coexistence with deafness of a specific defect of thyroxine synthesis, of a disorder of cardiac conduction, and of retinitis pigmentosa, in three distinct autosomal recessive syndromes, should afford clues to the nature of the biochemical pathways which are deranged as a result of the aberrant action of the mutant alleles which are responsible. That it does not do so at present may be attributable to the large lacunae which exist in our understanding of human metabolism, or possibly to a lack of application of inspired deductive reasoning to this problem. For example, if nothing were currently known of the biochemical basis of galactosemia, the existence of an autosomal recessive syndrome combining cirrhosis of the liver with lens defects might lead an astute observer to investigate galactose metabolism in affected persons. The possibility of further definition of genetically determined deafness by identifica tion of the gene loci involved, perhaps through linkage or biochemical data, will have considerable beneficial effects. These may be expected to be both therapeutic, in the same sense that a beginning has been made in mitigating the effects of inborn error of metabolism, such as phenylketonuria (and the suggestion [see page 150] that the cochlear damage in some forms at least of genetically determined deafness is not present at birth holds out some promise in this context), and preventive, in that problems of counseling will be simpler. Thus, in matings between persons with autosomal recessive deafness risk figures can be considerably refined, depending on whether the same or different gene loci are involved (see Chapter XVI), and improvements in heterozygote detection which will occur will improve the efficacy of counseling in other families also. The problem of the prophylaxis of primarily acquired deafness is far less complex and dependent only on advances in medical treatment and public health. Thus rubella embryopathy is largely preventable by vaccination programs, and improvements in the