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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    are among the most ubiquitous in human populations. As a result, such cases were ascertained in all the groups of the present survey. A definitive diagnosis that deafness is due to an allele potentially capable of giving rise to one of these conditions is often impossible because of variable expressivity and reduced penetrance, concepts discussed in footnote 13. Thus, deaf persons carrying such alleles may often not show any of the associated pigmentary or morphological anomalies, and the true situation may be revealed by the presence of these anomalies in their affected relatives, whether hearing or deaf. There are several reasons, however, why even such evidence may not be available. The index case may represent a fresh mutation, associated anomalies in relatives may be missed, especially when the family investigation cannot be accompanied by personal examination of all members, and even when there are several affected relatives who are deaf, the variability of expressivity of the allele may be such that none manifest the associated features. Thus in the discussion of ascertained cases which follows it must be clearly borne in mind that misdiagnoses may occur in both directions. On the one hand, as explained above, the presence of one of the alleles potentially capable of giving rise to these syndromes may not be recognized; on the other hand, such a syndrome may be falsely diagnosed on the basis of anomalies which are present fortuitously in the index case or in his relatives, whether hearing or deaf. 20 Brief clinical details follow concerning each case ascertained in whom the presence of an allele capable of causing dominant deafness with pigmentary anomalies is suspected. 21 It should be emphasized that these descriptions are based on family studies which are incomplete in the sense that only a proportion of relatives were visited, the main object being to establish the diagnosis in the index case rather than to identify the presence of the alleles concerned and to define their range of manifestation in all the members of the family. In many cases, reliance had to be placed on questionnaire information, correspon dence, and inspection of photographs. Thus, lack of mention of a specific close relative in the brief case reports which follow indicates that he was not profoundly deaf, but cannot be taken to be equivalent to the presence of normal hearing and the absence of the pigmentary and morphological anomalies associated with these auditory-pigmentary syndromes. Probable cases in the school study in the British Isles 1. Female. Both parents are deaf. She has a brother with normal hearing. She has uni lateral partial heterochromia with one blue iris and a segment of gray in the other, otherwise blue, iris. The blue segments of the irides show a hypoplastic stroma. Her father has a prominent white streak of hair. 2. Female. She has 2 sisters and a brother with normal hearing. Her mother has a mild unilateral loss of hearing. The patient has blue irides with a hypoplastic stroma. Her fundi are hypopigmented and she has marked lateral dystopia of the medial canthi, as has her mother who, in addition, has hair which began to go white in streaks at eighteen years of age and subsequently became extremely white. One of the patient's sisters has dystopia of the medial canthi as has 1 of 3 daughters of this sister. 3. Male. His sister, mother, and maternal uncle are partially deaf and his maternal grandmother is unilaterally deaf. All these relatives have lateral dystopia of the 20 For instance, heterochromia of the irides and white forelock undoubtedly occur in many cases entirely independently of this group of auditory-pigmentary anomalies. 21 Where the diagnosis of an auditory-pigmentary syndrome is certain, or where the index of suspicion is high, cases are defined as probable, whereas, when there is a substantial element of uncertainty, they appear as possible cases.