|
The management of genetic
disease can be divided into prevention and treatment. In the area
of prevention, major strides have been achieved through the processes
of genetic counselling, prenatal diagnosis, and genetic screening.
There have also been major advances in the treatment of genetic
disorders, although cures-in the sense of replacing defective
genes within the germ
line-have yet to be achieved. As described earlier, identification
of environmental mutagens
and prevention of exposure to them should become an effective
measure in preventing genetic disease.
Genetic counselling
represents the
most
direct medical application of the advances in our understanding
of basic genetic mechanisms. The counselling usually stems from
an inquiry about whether a given disease is likely to recur in
a family. Its chief purpose, therefore, is to help people make
responsible and informed decisions concerning reproduction and
to understand their options. Another aim is the early diagnosis
and management of genetic disorders.
Most couples
who present themselves for preconceptional counselling fall into
two categories: those who have had a child with genetically based
congenital
malformations or developmental delays, and those who have one
or more relatives with a disease they think might be inherited.
The counsellor must determine the diagnosis in the affected person
(the propositus) with the most meticulous accuracy, so as to rule
out a genocopy or phenocopy.
A careful family history permits construction of a pedigree that
may illuminate the nature of the inheritance (if any), may affect
the calculation of risk figures, and may bring to light other
genetic influences. The counsellor, usually a physician with special
training in medical genetics, must then decide whether the disease
in question has a strong genetic component and, if so, whether
the heredity is single-gene, chromosomal, or multifactorial.
In the case
of single-gene inheritance, the disease may be passed on as an
autosomal recessive, an autosomal dominant, or a sex-linked recessive.
If the prospective parents already have a child with an autosomal
recessively inherited disease, they are by definition carriers,
and there is a 25 percent risk that each future child will be
affected. If one of the parents has an autosomal dominantly inherited
disease, there is a 50 percent risk that each future child will
be affected. If, however, the couple has borne a child with an
autosomal dominantly inherited disease but neither parent carries
the gene, the presumption is that a spontaneous mutation has occurred
and that there is not an increased risk for recurrence of the
disease in future children. If the pedigree or carrier testing
suggests that the mother carries a gene for a sex-linked disease,
there is a 50 percent chance that each son will be affected.
Counselling
for chromosomal inheritance most
frequently
involves an inquiring couple (consultands) who have had a child
with Down syndrome showing the usual trisomy
21 chromosome constitution. An empirically determined risk for
recurrence of 2 percent is given, unless other predisposing factors
are present.
Most of the
common hereditary birth defects are multifactorial. If the consultands
have had one affected child, the empirical risk for each future
child is about 3 percent. If they have borne two affected children,
the chance of recurrence rises to about 10 percent.
After determining
the nature of the heredity, the counsellor discusses with the
consultand the odds and the stakes, the odds being the statistical
risk of recurrence, and the stakes being a consideration in detail
of the burden both to a future child and to the family if the
particular disease should occur.
The counsellor
then presents to the consultands various options for their consideration.
Depending on the nature of the inheritance, these options may
include any of the following choices.
- Accept
the risk and take a chance that the future baby will be unaffected
or, if affected, will be amenable to therapy.
- Utilize
sperm from a stranger for artificial insemination. This option
is a good genetic solution only if the husband has a dominantly
inherited trait or if both parents are carriers of a rare recessively
inherited trait.
- Employ
intrauterine
diagnosis with selective abortion of affected fetuses if the
condition is one that can be diagnosed by this method (see below).
- Decide
against reproduction because the risk is unacceptable; possibly
adopt a baby instead.
Counselling
in general is "nondirective." The counsellor's function is to
help the couple make an informed decision about reproduction and
then to support that decision. One other opportunity the counsellor
has is to identify those relatives of the propositus who are unaware
or misinformed of their risks of having affected offspring.
Rick
Weiss
|