The Principles of Clinical Cytogenetics - Extra Materials - Springer

556 Sarah Hutchings Clark
Although, as previously stated, mosaic chromosome abnormalities can be associated with milder
phenotypes, the clinical features associated with true mosaicism cannot be entirely accurately predicted
from the karyotype. One reason for this is that it is impossible to know the distribution of
normal and abnormal cells in the various tissues of the body. In some cases, there can, however, be a
correlation between the percentage of abnormal cells and the degree of abnormality. A review of the
pertinent literature might provide useful information regarding the general phenotype (44–47).
It has been estimated that the prevalence of supernumerary marker chromosomes at the time of CVS
and amniocentesis is approximately 0.6–1.5 per 1000 (48). The identification of such a marker can
create a frustrating situation for the parents, as there is a lack of substantial information about many of
these markers. The limitations of prenatal ultrasound in identifying fetal abnormalities can often compound
this frustration. The risk for abnormalities in the light of a marker chromosome can depend on
the amount euchromatin present, whether the origin of the marker is an acrocentric or nonacrocentric
chromosome, whether the marker is familial or de novo, and, if familial, whether the marker is found in
a mosaic state in the carrier parent (48). One source quotes a 10.9% risk for abnormality associated with
a de novo satellited marker and a 14.7% risk for a de novo nonsatellited marker (43).
Certain markers are, however, associated with well-defined clinical features. For example, an
isochromosome for the short arm of chromosome 12 [i(12p)] causes Pallister–Killian syndrome,
which is associated with profound mental retardation, seizures, characteristic facial features, and
pigmentary abnormalities. Cat-eye syndrome, which is usually caused by a marker that results in
tetrasomy 22q11.2, can be highly variable and can cause mental retardation, as well as abnormalities
involving the eyes, heart, and urogenital system. Additionally, the “inverted duplicated 15” [inv
dup(15)] can be associated varying features, ranging from mental retardation and clinical features of
Prader–Willi/Angelman syndrome to a normal phenotype (48). See Chapters 8 and 9.
SUMMARY
Genetic counseling is a complex, fascinating, and continuously evolving field. With the current
focus of science and popular culture on genetics, genetic counseling is becoming increasingly important
in medicine. As stated in the beginning of this chapter, genetic counselors are increasingly found
in a wide variety of settings in clinical, research, and administrative roles. Furthermore, genetic counselors
can contribute significantly, not just in the setting of prenatal genetics, but also in the pediatric
and adult arenas.
Counselors not only play a vital role in explaining genetic concepts, recurrence risks, and genetic
testing in understandable terms, but also in helping individuals anticipate and cope with the psychosocial
consequences that can be associated with the diagnosis of a genetic condition. Although seemingly
straightforward, these can be challenging tasks, particularly when ambiguous test results,
cultural differences, and/or mental handicaps are involved. The unique training that genetic counselors
receive makes them especially well suited to tackle such challenges.
Ethics and genetics are closely intertwined, as genetic counselors continuously encounter a variety of
situations in which ethical principles and guidelines must be consulted and followed. These situations
range from the fairly routine to the more obscure. There are several resources at the counselor’s disposal
that provide assistance in working through such ethical dilemmas. With the continuing development of
new technologies in the field of genetics and the revealing of the genetic contributions to human life and
disease, particularly in the realm of genetic predisposition to adult-onset conditions, the public, government,
and scientific communities will surely face increasingly complex ethical dilemmas.
REFERENCES
1. National Society of Genetic Counselors (1983) Genetic Counseling as a Profession. National Society of Genetic Counselors.
2. Resta, R.G. (1997) The historical perspective: Sheldon Reed and 50 years of genetic counseling. J. Genet. Counsel.
6(4), 375–377.