The Principles of Clinical Cytogenetics - Extra Materials - Springer

550 Sarah Hutchings Clark
SMITH–MAGENIS SYNDROME
Smith–Magenis syndrome, which is the result of a deletion involving the short arm of chromosome
17 [del(17)(p11.2p11.2)], is usually sporadic. In infancy, individuals with Smith–Magenis syndrome
tend to have feeding problems and low muscle tone. Language and motor skills are delayed,
and mental retardation is a feature of the condition. Other features include short stature, poor sleep
patterns after infancy, characteristic facial features, and behavioral problems. The behavioral problems
often include self-injury, attention deficit, and temper tantrums (15).
MILLER–DIEKER SYNDROME
Miller–Dieker syndrome is also the result of an interstitial deletion involving the short arm of
chromosome 17 [del(17)(p13.3p13.3)], more distal than that seen in Smith–Magenis syndrome.
The abnormalities associated with this condition involve the central nervous system, with lissencephaly,
or a smooth brain, being a characteristic feature. This results in severe mental retardation,
seizures, low muscle tone, and a small head size. Certain characteristic facial features are also
associated with Miller–Dieker syndrome. The majority of affected individuals die within the
first 2 years of life (18).
Subtelomere Rearrangements
Cryptic microdeletions, or subtle rearrangements near the tips of chromosomes, are estimated to
be a common cause of mental retardation, with or without dysmorphic features. Unbalanced
subtelomere rearrangements are reported to occur in 7.4% of individuals with moderate to severe
mental retardation (19) and can be detected with FISH probes for the unique subtelomeric regions of
most chromosomes (see Chapter 17). The identification of such an unbalanced rearrangement in a
phenotypically abnormal individual allows subtelomeric FISH studies to be offered to the parents,
and other at-risk family members, to determine if one of them carries a balanced subtelomeric rearrangement.
Based on the results of the parental analyses, recurrence risks can be more accurately
quoted. Certain other clinical indications for subtelomere analysis, such as characterization of known
chromosomal abnormalities, have been noted in the literature (20,21).
Chromosome Instability Syndromes
As discussed in Chapter 14, there are a number of genetic syndromes of which a notable feature is
an increased incidence of chromosome breaks and instability. The majority of these syndromes,
including Fanconi anemia, Bloom syndrome, ataxia telangiectasia, and Roberts syndrome, follow an
autosomal recessive pattern of inheritance. Therefore, the presence of one of these conditions in a
family can have significant implications for recurrence (15).
Infertility
At times, when one of the members of a couple is a carrier of a structural chromosome rearrangement
(see Chapter 9), the unbalanced segregation of that rearrangement can result in miscarriage
before the couple is aware of the pregnancy. This can cause the couple and their physicians to suspect
infertility. True infertility is also a frequent feature of certain sex chromosome abnormalities, and,
therefore, the clinician and genetic counselor must also consider the possibility of a sex chromosome
disorder when faced with an infertile couple. See also Chapters 10 and 11.
Sex Chromosome Abnormalities
It has been estimated that, overall, approximately 1/400 infants have some form of sex chromosome
aneuploidy (22). A thorough discussion of sex chromosomes and sex chromosome abnormalities
can be found in Chapter 10. A potentially challenging situation that genetic counselors face
regarding the diagnosis of a sex chromosome abnormality is that the patient is often an adolescent. It
is imperative for the counselor to discuss this finding and its implications on the patient’s level of
understanding. Additionally, he or she must appreciate that the diagnosis might create for a young