Young: Medical Genetics 
Multiple Choice QuestionsYoung: Medical Genetics
Example 1
Parents are referred to the genetics clinic following the discovery that their three year old son shows evidence of significant developmental delay (see pages 254-257 for how this should be investigated).
Step 1 – the nuclear family
The parents are asked about other children and pregnancies. The mother (women nearly always know more about family history than men – sometimes they even know more about their partner’s family history then he does!) indicates that she and her partner have 3 children, two daughters and one son.
Step 2 – the parents’ nuclear families
Next information is sought about each of the parents, beginning with their siblings and their own parents, i.e. the proband’s grandparents. The boy’s father indicates that he has one brother and one sister. His brother has no children. His sister has two sons. Both of his parents are alive and well. The boy’s mother states that she also has one brother and one sister. Her sister is well and has one son and one daughter, but her brother has significant learning difficulties and lives at home with her parents who are both well.
Step 3 – the extended family
Information about more distant family members is often limited but it is well worth exploring this as far as possible to try to ensure that all relevant information is obtained. In this family it emerges that the proband’s maternal grandmother had a brother who was ‘slow’ and who died in late childhood as a result of pneumonia. This boy had never attended school and did not start talking until the age of 6 years.
Step 4 – any other information
Finally it is important to check about other relevant family details. This should include an enquiry about possible consanguinity, particularly involving the parents of the proband, and whether there is any other family history of note. In this example the parents were sure that they were not close relatives and, apart from a history of adult onset diabetes in the father’s family, they were not aware of any other problems which might have a genetic basis.
Comment – in this situation the construction of a family tree has revealed a significant history of learning problems in the mother’s side of the family. All three of the affected boys are related through the maternal line with no intervening unaffected males. This points strongly to X-linked recessive inheritance, which would prompt investigation for one of the many X-linked causes of mental retardation (page 256). This conclusion would also have implications for the affected boy’s sisters when they grow up and for their female first cousin, the daughter of their maternal aunt. The probability that this first cousin would be a carrier of this X-linked condition can be calculated using Bayes theorem to be 1 in 6. (This is explained on pages 251-253).
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