Division of Medical Genetics, Department of Genetics and Microbiology,
University Medical Centre, 1211 Geneva 4, Switzerland
Not so long ago medical genetics was perceived as a highly specialized
branch of medicine, of relatively little importance to the general public,
and many doctors considered training in genetics a luxury. Such attitudes
have largely changed today, with the recognition that many common disorders
have at least partial genetic origin, and with the rapid development of
powerful diagnostic tests for both chromosomal and single gene disorders.
Some knowledge of genetics is considered as essential today for any health
Some 2-3% of infants are born with congenital malformations, the majority
of which have at least a partially genetic basis. And if one considers the
causes of illness in persons up to the age of 25 years or so, at least 5%
of all individuals will suffer by adulthood from a malformation or disease
with a major genetic component. (Baird et al., 1988). Thus, the comprehension
and control of genetic disorders is, particularly with regard to the decline
in mortality and morbidity from infectious disease, a major public health
What is genetic counseling?
Genetic counseling may be described as the process through which individuals
affected by, or at risk for a problem which may be genetic or hereditary,
are informed of the consequences of the disorder, of the probability of
suffering from or of transmitting it to their offspring, and of the potential
means of treating or of avoiding the occurrence of the malformation or disease
in question. Genetic counseling in common disorders is often given by the
family doctor, the pediatrician or the obstetrician. However, with the recognition
that thousands of problems have a major hereditary component, counseling
is increasingly done in specialized centers which also provide the laboratory
diagnostic tools which we hear so much about in our era.
Four aspects are involved in giving genetic counseling:
- Arriving at a specific diagnosis: this is often the most
difficult, trying and time consuming part of the process, for the health
care professionals as well as for the family (who are understandably
more concerned with the care of their affected relative, than with the
specific name of his or her disorder). However, without a correct diagnosis,
counseling is at best incomplete and imprecise.
- Estimation of risks: to develop the disorder and/or to transmit
it to offspring.
- Practical aid: this includes, for example, recommending doctors
for specialized examinations or health care professionals for speech
or educational therapy. It often implies as well the coordination of
prenatal and other diagnostic tests.
- Supportive role: this aspect is at least as important as
the diagnostic question, for the great majority of genetic disorders
cannot be cured or even satisfactorily treated. Although the genetic
counselor cannot provide support for the family on a daily basis, he
or she should be able to orient them towards those health professionals
who can best serve them in this role. Accepting and learning to live
with a genetic diagnosis is particularly difficult when reproductive
options are involved, and feelings of " guilt " may touch several generations
and cause rifts in the family just at the time when solidarity is most
What types of disorders are genetic?
" Genetic " does not necessarily mean " hereditary ". The first term
implies simply that the genetic material, on a chromosomal or a gene level,
contains one or more mutations which are the cause of the disorder. Once
a mutation is present in a patient, particularly if it is constitutional
(and thus present in all cells), it can of course be transmitted and thus
becomes a hereditary disorder.
Genetic disorders are generally of four types:
- Chromosomal disorders: affect some 1/200 live-born children
(Robinson & Puck, 1967), and about 1/500 adults. Abnormalities of chromosome
number are rarely inherited, although affected individuals who
reproduce may transmit the extra chromosome to their offspring. Structural
abnormalities, such as translocations in which two chromosomes exchange
segments, may cause little or no effect in carriers, but predispose
to reproductive problems such as miscarriage and infertility.
- Monogenic (" Mendelian ") inheritance: is the result of mutations
in single genes, at specific gene " loci. " We have some 50-100,000
individual genes, for several thousand of which monogenic disease has
been described (McKusick, 1992). Some 1/300 individuals will suffer
from a monogenic disease manifesting within the first two decades (Baird
et al., 1988), but this figure may be as high as 1% if the lifetime
probability of manifesting a monogenic disorder is considered. Four
types of transmission are observed in monogenic disorders caused by
nuclear genes: autosomal dominant (one mutated gene of the pair
is sufficient to produce symptoms), autosomal recessive (the
two alleles must be abnormal to cause the phenotype) and X-linked,
which includes recessive (theoretically, only males suffer,
given that they are " hemizygous " for the X chromosome) and, less frequently,
X-linked dominant gene mutations (males more seriously affected
than females). A few genes, involved particularly in sex determination
and fertility, have been localized on the Y chromosome, the transmission
of which is only from a father to his XY offspring.
- Polygenic or " multifactorial ": although this causation
is not " as genetic " as are monogenic and chromosomal disorders, the
majority of malformations and of common familial disorders have this
type of cause. Polygenic implies that the association of several different
genes, each one slightly modified, is necessary to produce the disorder.
Multifactorial causation means that both genetic and non-genetic (environmental,
either pre- or postnatal) factors are associated to produce the pathology.
Some 5-10% of the population will suffer either from a malformation
or from a disease in which genetic factors are major.
- Mitochondrial disorders: In recent years a " new " type of
inheritance has been proven, that resulting from mutations in the mitochondrial
genome. Each cell contains hundreds or thousands of mitochondria, each
containing one or several circular chromosomes. These chromosomes can
be deleted or suffer other types of mutations which interfere with cellular
production of ATP, and thus of the energy vital for the cell/organ/organism;
the symptoms depend on the tissues involved and on the proportion of
mitochondria mutated, but involve first the central nervous system and
the muscle, due to their large energy demands (Morris, 1990; Wallace,
1993). The incidence of mitochondrial mutations in human disease is
still unknown. In many cases the mutation is " de novo " in an affected
individual, but hereditary transmission is purely maternal, since,
a fertilized egg’s mitochondria originate from the maternal germ cell
Who seeks genetic counseling?
In most genetics divisions patients can either come self-referred or
be recommended by a physician. Currently, genetics has not evolved to a
state of knowledge where couples come for " genetic screening " without
a specific family history or increased risk for a genetic disorder for another
reason. The day will probably come in the not too distant future when preconceptional
or prenatal screening can be offered to the general population for a panel
of different diseases. However, for the moment only several dozen of our
50,000-100,000 individual genes have been identified and their mutations
defined. Testing for any one of these requires both technical competence
and a considerable investment of time and money. The reasons for seeking
genetic counseling can be divided into the following six categories:
- The individual (often hoping to be a parent) suffers himself
form a genetic or potentially genetic disease. This may be a (relatively
unsevere) chromosomal disorder, a single gene condition (transmitted
in a dominant, recessive or X-linked manner), or a " multifactorial
" disorder, e.g. implying the combined effects of a genetic predisposition
and unfavorable environmental factors (for example, diabetes or epilepsy).
- A close relative has a genetic disease, and the individual
who consults is worried either about his/her own risk of developing
the disease, or the risk that his offspring will suffer from the disorder.
- The individual is at increased genetic risk for a specific genetic
disorder given his or her particular ethnic origin. Each population
has one or more genetic diseases, generally transmitted as autosomal
recessive traits, which are particularly frequent within it, e.g. cystic
fibrosis in white Europeans and sickle cell anemia in Africans and Mediterranean
populations. A similar situation may apply to couples who are consanguineous
(blood relatives), although there is no way of determining which specific
genes or diseases are implied, unless this is indicated by a positive
family history for a particular disorder.
- The individual or couple is having reproductive problems, e.g.
infertility, repeated miscarriage, etc. Such problems may have genetic,
particularly chromosomal causes. The individual may be initially referred
for a laboratory diagnostic test, with counseling differing markedly
depending on the result of the analyses.
- The couple has already born a child or fetus with a malformation
or genetic disorder. In this situation the specific diagnosis may
be known or not, and the risk of recurrence vary from less than 1% up
- The couple requests counseling, concerning prenatal diagnosis,
for such reasons as advanced parental ages,. Amniocentesis or choriocentesis
should be offered to women of 35 years and older, given their increased
risk of bearing a child with a chromosomal anomaly. Counseling sessions
for older parents, or for those requesting prenatal diagnosis because
of anxiety (close contact with a handicapped individual, for example)
are intended to provide information concerning the benefits and risks
inherent to prenatal diagnostic techniques.
In all these situations, genetic counseling should be, in so far as is
possible, impartial and nondirective. The goal is never to make a decision
for the couple, whose familial, social, moral and religious situation
is different from that of the counselor, but rather to provide them
with the objective information which will allow them to make their own informed
What information is sought in genetic counseling?
Unless a specific diagnosis has already been proven, the first
and foremost concern is to establish, if at all possible, the identity of
the disorder. If and when this is done, the geneticist must often review
the literature, as well as count on his own experience, in order to inform
consultants as precisely as possible of the etiology of the problem.
Of primary concern to the family is of course the natural history of
the genetic disease, which includes prognosis and discussion of potential
treatments and of practical guidelines in how to deal with these. Even
if not an initial concern for those seeking counseling concerning a child
recently born, the question of recurrence risks must be rapidly discussed,
as well as possibilities for prenatal diagnosis if such is desired
by the family. This in itself is often a difficult task, as necessary information
about a particular disorder or diagnostic technique may be sparse, and couples
may directly ask what the counselor for directive advice.
What does a genetics work-up involve?
From the geneticist’s point of view, and in order to more efficiently
counsel a given family, it is preferable to obtain and review medical documents
in advance, as well as to review recent literature on the problem to be
treated. Once a family arrives in the genetic clinic, the steps to be taken,
depending on whether the specific diagnosis is established, can be summarized
- Obtaining a detailed family history, which includes both
sides of the family even if counseling has been requested for a
dominant disorder affecting one parent. It is not rare that in taking
such a history, other antecedents are revealed which also merit
- A review of medical and/ or pregnancy histories is especially
important when the diagnosis is not yet established, but also helps
geneticists to learn more about etiologies and natural histories
of certain disorders.
- A physical examination, of the affected person, and sometimes
of other family members, is often needed.
- Medical and/or laboratory exams may be suggested. If
a diagnosis has not been established these often include chromosome
study, and may necessitate DNA analysis if the identity of the gene
suspected to be involved is known. Other frequent suggestions include
X-ray or ultrasound examinations, and various biochemical analyses.
Once the diagnosis is known, medical tests aimed at evaluating health
risks linked to the disorder may also be established.
- Genetic counseling can only be given at the end of this
The process of genetic counseling has changed dramatically over the past
25 years. Instead of being based on purely clinical findings, the identity
of many disorders can be proven because their genic or chromosomal basis
is known. The availability of an ever-increasing number of laboratory tests
allows more accurate diagnosis, and often gives the opportunity for pre-symptomatic
or prenatal diagnosis to family members who prefer to use it. However, it
must not be overlooked that the availability of such tests also poses psychological
and ethical questions which are difficult to resolve. A sub-speciality of
medical genetics has thus evolved which examines the individual’s and the
society’s means and ways of resolving such questions ( Wertz and Fletcher,
The training of individuals competent to give genetic counseling has
been formalized in a number of European countries, as was done in the United
States and Canada a number of years ago through their respective Boards
of Medical Genetics. Medical doctors with post-graduate training in medical
genetics depend heavily on cytogeneticists and molecular geneticists for
diagnosis, as well as, increasingly, on genetics " associates " (master’s
degree geneticists and nurse specialists) and Ph.D. medical geneticists
to help both with the initial work-up and with follow-up of families. As
genetics has become a bona fide speciality in itself, with training programs
developing for health professionals at various levels. Most training is
done in university medical genetics departments.
What services are offered by most university genetics
To provide both diagnostic, counseling and follow-up services, close
ties must be established with such hospital departments as pediatrics and
obstetrics and access to specialized diagnostic services and to medical
library facilities is essential. However, a number of services are best
offered within one unit:
- Clinical diagnosis and genetic counseling.
- Chromosomal analysis: both postnatal and prenatal diagnostics.
- DNA extraction and banking.
- DNA analysis.
- Prenatal diagnostic services.
Cited in the text
- Baird, P.A., Anderson T.W., Newcombe H.B., and Lowry RB (1988):
Am. J. Hum. Genet., 42:677-693.
- McKusick, V.A. (1992): In: Mendelian inheritance in man,
10th ed. The Johns Hopkins University Press, Baltimore.
- Morris, M.A. (1990): J. Clin. Neuro-Ophthal., 10:159-166.
- Robinson, A., and Puck, T. (1967): Am. J. Hum. Genet., 19:112-129.
- Wallace, D.C. (1993): TIG, 9:128-133.
- Wertz, D., and Fletcher, J.C. (1989): In: Ethics and human genetics:
a cross-cultural perspective. Springer-Verlag, Berlin.
- Gelehter, T.D., and Collins, F.S. (1990): In: Principles of medical
genetics. Williams & Wilkins, Baltimore.
- Harper, P.S. (1988): In: Practical genetic counseling. Wright,
- Thompson, M.W., McInnes, R.R., and Willard, H.F. (1990): In:
Genetics in medicine. W.B. Saunders Co., Philadelphia.
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Edited by Aldo Campana,