Personal Practice

Amita Pandey

From the Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, India.

e-mail:shubha@sgpgi.ac.in

Because of rapid advances in molecular genetics over the last few decades, there is a tremendous increase in the knowledge about genetic diseases. This information is finding applications in clinical management of diseases in the form of genetic counseling, carrier detection, presymptomatic and prenatal diagnosis. With better control of infectious and nutritional diseases, genetic diseases have lately emerged as a significant cause of morbidity and mortality(1). As most of the genetic diseases present early in life, it is of utmost importance for pediatricians to realize the importance of genetic counseling in the management of children with genetic disorders and to develop the necessary expertise.

Definition of Genetic Counseling

The American Society of Human Genetics defines(2) genetic counseling as a communicative process which deals with the human problems associated with the occurrence or risk of recurrence of a genetic disorder in a family. This process involves an attempt by one or more appropriately trained persons to help the indiviudal or family to: (i) Comprehend the medical facts including the diagnosis, probable course of disorder and the available management; (ii) Appreciate the way heredity contri-butes to the disorder and the risk of recurrence in relatives; (iii) Understand the alternatives for dealing with the risk of recurrence; and (iv) Choose the course of action which seems to them appropriate in view of this risk, their family goals, ethical and religious standards and to act in accordance with that decision to make the best possible adjustment to the dis-order in an affected family member and/or to the risk of recurrence of that disorder.

The person who seeks genetic counseling is called the consultand or counsellee and the one who gives it is the counsellor. In addition to medical specialists, trained persons with various backgrounds like nursing, social work education and psychology can function as genetic counsellors.

From the definition, it is clear that the objective of genetic counseling is to make the individual or the family to understand the scientific information about the disease, thus helping them to cope with the problem of genetic disorder and to reach a reproductive decision.

Indications for Genetic Counseling

The common indications for genetic counseling in clinical practice are as follows:

1. Presence of congenital malformation(s) in a child or stillbirth or in a fetus.
2. Mental retardation with or without mal-formations or dysmorphism.

3. Skeletal dysplasia-Disporportionate short stature.
5. Neurodegenerative diseases, e.g., ataxias, leukodystrophy.
6. Myopathy.

7. Known genetic diseases, e.g., thalas-semias, Wilson disease, hemophilia, mucopolysaccharidosis.
8. Down syndrome and other chromosomal disorders.
9. Relatives of a person with chromosomal translocation.
10. Consanguineous marriage.
11. Advanced maternal age.
12. Exposure to known or suspected teratogen during pregnancy.
13. Any disease if it appears familial.
14. Any unusual disease of skin, eyes, bones, or unusual facial features.
15. Deafness.
16. Familial cancers or cancer prone disease.
17. Ambiguous genitalia or abnormalities of sexual development.

Steps in Genetic Counseling

Genetic counseling is a multistep process and involves clinical expertise similar to any other medical speciality. The steps are history taking, pedigree construction, examination, diagnosis, counseling and follow up. A standard medical history is required for the proband (affected individual who draws attention to the family) and for other affected persons in the family.

Pedigree

Next the pedigree (at least 3 generations) is constructed using standardized set of symbols (Fig. 1). Direct questions need to be asked for similarly affected individuals, miscarriages, early deaths, consanguinity, major and minor malformations.

Examination

A complete physical examination and relavent anthropometric measurements are necessary. In a case with dysmorphology correct description of facial features, minor malformations, normal variants need to be noted down. A photographic record of dysmorphic child is essential as it is much better than a lengthy description. Examination of parents may be needed to verify whether a dysmorphic feature (e.g., shape of ears) is of diagnostic significance or a normal familial feature in that family.

Investigations and Diagnosis

The importance of precise diagnosis for genetic counseling can not be overemphasized as there may be apparently similar looking disorders caused by different genes (genetic heterogeneity) or environmental factors. The various hematological, biochemical and imaging investigations suffice many genetic diseases while for some cases specialized tests like chromosomal analysis, enzyme assays, aminoacid levels, or molecular studies may be needed.

Indications for Chromosomal Analysis

The usual indications for chromosomal analysis include: (i) Confirmation or exclusion of the diagnosis of known chromosomal syndromes, for example Down Syndrome; (ii) Unexplained psychomotor retardation with or without dysmorphic features; (iii) Abnormalities of sexual differentiation and development; (iv) Infertility; (v) Two or more than two monogenic disorders in a patient; (vi) Monogenic disorders associated with mental retardation and/or dysmorphic features; (vii) Recurrent miscarriages or still births; (viii) Multiple malformation syndrome; (ix) X-linked recessive syndrome manifesting in a female; and (x) Pregnancy at a risk of aneuploidy because of previous chromosomally abnormal child, maternal serum screening, advanced maternal age, or abnormality detected on fetal ultrasound scanning.

There is little point performing chromosomal analysis on patients with single congenital malformation, single gene disorders or with recognizable non chromosomal syndrome. However, a chromosomal analysis of a clinically obvious Down syndrome child is extremely important, because depending on the type of chromosomal anomaly, the risk of recurrence may vary from 1% to 100% (Table I).

Fig. 1. Symbols commonly used in drawing a pedigree.

Table I^__ Recurrence Risk of Down Syndrome

Karyotypes of Patient

Father

Mother

Chance of    Recurrence (%)

N 

C

10-15

C

N

5 

N

C

10-15

C

N

5

N

C

100  

C

N

100

Trisomy 21

N

N

1

N

N

Small

C = Carrier; N = Normal.

DNA Diagnosis

As more and more disease related genes are getting mapped and sequenced, the DNA diagnostic tests are becoming available for single gene diseases. Currently DNA diag-nosis for Thalassemia, Hemoglobinopathies, Hemophilia, Duchenne muscular dystrophy, Fragile-X-mental retardation and Spinal muscular atrophy are available in India. For providing prenatal diagnosis, the DNA diagnosis of the affected child in the family needs to be done beforehand.

Investigations of Family Members

A careful clinical examination and investigation of parents and family members for mild manifestations can be of great use in genetic counseling as variable expression is characteristic of many autosomal dominant conditions; for example, parents of a child with tuberous sclerosis or neurofibromatosis. If one of the parents is having any feature of tuberous sclerosis, then the risk of recurrence is 50% while in case both the parents are normal, there is no significantly increased risk of recurrence. Similarly, a single central incisor in a parent of a child with holoprosencephaly will suggest autosomal dominant inheritance.

Syndrome Diagnosis

Multiple malformation syndromes with or without mental retardation is an important group of patients needing genetic counseling. With an evergrowing list of syndromes, reaching an exact diagnosis may be difficult. The situation is greatly helped by various computerized databases, namely, London Dysmorphology Database and Pictures of Standard Syndromes and Undiagnosed Malformations (POSSUM). Referring to the books giving detailed descriptions of syndromes and diagnostic approaches is also of great help(3-6).

Counseling

Accurate diagnosis is of paramount importance for meaningful genetic counseling. Other requisities are a quiet, comfortable room and adequate time. The counsellor should be a good sympathetic listener with good communicative skill. He should give information in simple nontechnical and local language. Counseling needs to include all aspects of the condition and the depth of explanation should be matched to the educational background of the couple. Natural course of the disease and treatment (sometimes only supportive) should be highlighted. The risk of recurrence should be explained, if necessary with the help of diagrams. The risk, for example 1 in 4 should be explained in both ways, i.e., 1 in 4 and 25%. It should be made clear that there may be 2 or 3 or more consecutively affected children in a family as chance does not have memory. The probability can be explained by an example of tossing a coin or like. It is often useful to compare this recurrence risk against the general population risk for the condition and for common birth defects (Table II). It should be stressed that any family can have children affected with genetic diseases or congenital malformations and parenting such a child or carrier status for genetic disease is not a stigma nor should be considered a discriminating factor. A common misconception about heredity may also need to be dispelled.

The last and the most important part of the counseling is about reproductive options. Depending upon the parents judgement about the risk of recurrence, they may go for contraception, adoption, in-vitro fertilization or further pregnancy with or without prenatal diagnosis. The family may need to be referred to a genetic center for getting the latest information about the disease and facility for prenatal diagnosis. The list of some of the genetic centers in India is given in Table III.

Table II^__Empiric Risk of Recurrence of Isolated Malformation.

Frequency per 1000 births

Recurrence (%) for normal
parents of one affected child

4-5 

5

6-8

3-4

2

4-5

0.5

2-6

2-3

3

3-4

2-8

3-4

3-4

0.1

6

Table III^__Genetic Centers in India.

1. Center for Genetic Disorders, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab.
2. Department of Human Genetics and Anatomy, St. Johns Medical College, Bangalore.
3. Department of Pediatrics, K.E.M. Hospital, Mumbai.
4. ICMR Immunohematology Center, KEM Hospital. Mumbai.
5. ICMR Genetic Research Center, Indian Council of Medical Research, Wadia Hospital for Children, Mumbai.
6. Department of Genetics, Ramakrishna Mission Hospital, Calcutta.
7. Departments of Pediatrics and Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh.
8. Genetics Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.
9. Department of Genetic Medicine, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi.
10. Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow.
11. Department of Genetics, Instiute of Child Health and Institute of Obstetrics and Gynecology, Chennai.
12. Genetics Center, Department of Pediatrics, B.J. Medical College, Pune.