Counseling in medical genetics / Sheldon Reed.

  • Sheldon Clark Reed
Date:
[1980]
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Counseling in medical genetics / Sheldon Reed. Source: Wellcome Collection.

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    30 / Diagnosis and Genetic Heterogeneity Dihydropteridine Reductase Deficiency Mistaken diagnoses are not a relic of the past but continue into the present. The article by Kaufman et al [1975] is an interesting account of a case of dihydroperi- dine reductase deficiency that was misdiagnosed as classical phenylketonuria. This error had severe medical consequences, though the genetic counseling risk would have been the same (25%). The parents of the patient were first cousins. The diagnosis of a trait may be easy in some cases even though there may be great variation in expression of the trait from patient to patient. Such variability will often be due to genetic modifiers and environmental differences. The constellation of small genetic and environmental modifiers must be enormous. One can hope, at best, to identify some of the major factors involved. Tlie severity of a particular trait may vary from one group of family members to another. One kinsliip may have early onset of a trait wliile in another kinship the affected members will display a late onset. Difficulties With Down Syndrome There may be problems with traits where the diagnosis is uncomplicated, as with the Down syndrome. Here, one of the parents could be a chromosomal mosaic for the trait with an increased risk of a repetition of the trait in a subsequent child. One of the parents could be a carrier of a chromosomal translocation with a sub¬ stantially increased risk, about 10%, of a repetition. The most usual case would be that the Down child resulted from chromosomal nondisjunction, with only a small risk in the neighborhood of 1% of a repetition of the syndrome in a sibhng. The problem of obtaining a correct diagnosis is thus a difficult one from many points of view, and the genetic counselor should not shirk his duty to search out the speciaUst who can provide the best diagnostic service in order that the genetic counseling be based upon scientific fact and not fancy. The diagnosis and genetic heterogeneity may be related to each other in a practical way. For instance, the same bony alterations are found in autosomal recessive Hurler syndrome as in the X-linked Hunter syndrome. However, if corneal clouding is present, we have Hurler but not Hunter. Other diagnostic differ¬ ences give a clear distinction between the two superficially similar appearing syndromes. Genetic counseling will be different for an autosomal compared with an X-linked trait, so the correct diagnosis resolves the genetic heterogeneity very nicely. Dr. Huntington recognized head bobbers in one of his Huntington's chorea families as different from the behavior in his other choreic families. Probably there was more than one dominant mutation for the trait among his families; these dominant mutations may have occurred independently in different founding fathers. I am unaware of any Huntington disease cases where any Mendehan mechanism other than dominance was present. Consequently, genetic counseling can be done with some confidence that a Mendelian dominant gene is involved.
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