The Principles of Clinical Cytogenetics - Extra Materials - Springer

Genetic Counseling 549
Microdeletion Syndromes
Microdeletion syndromes, as their name implies, are the result of relatively small chromosomal
deletions that are usually undetectable via routine cytogenetic analysis. When a clinician suspects
that an individual is affected with one of these conditions, FISH techniques are generally employed
to confirm, or rule out, the diagnosis. Occasionally, certain ultrasound findings raise the possibility
of a particular microdeletion syndrome in the fetus, as can be the case with DiGeorge syndrome when
a heart defect is noted on prenatal ultrasound. In these cases, FISH analysis can be performed on the
material obtained from a chorionic villus sampling (CVS) or amniocentesis. Several of these
microdeletion syndromes occasionally result from the unbalanced segregation of a familial chromosome
rearrangement. See Chapters 12 and 17.
DIGEORGE SYNDROME/VELOCARDIOFACIAL SYNDROME (VCFS)
This syndrome results from a deletion involving the long arm of chromosome 22 [del(22)
(q11.21q11.23)]. One interesting feature of this condition is the potential for wide clinical variability
within and between families. At times, subsequent to the diagnosis of a child, one of the parents is found to
be affected, although usually more mildly. The microdeletion can be sporadic, but it can also be inherited
in an autosomal dominant manner. A variety of features in multiple organ systems have been reported in
individuals with DiGeorge syndrome. Some of the more common features include learning disabilities,
heart defects, cleft palate, short stature, immune problems, low muscle tone in infancy, hypernasal speech,
low calcium levels, renal abnormalities, mental illness, and characteristic facial features (18).
PRADER–WILLI SYNDROME
Approximately 70% of cases of Prader–Willi syndrome result from deletion on the paternally
derived copy of chromosome 15 [del(15)(q11.2q13)]. Other potential causes are maternal uniparental
disomy for chromosome 15 and an imprinting mutation. Imprinting refers to certain genes being
active on only the maternally or paternally derived copy of a particular chromosome (see Chapter 19).
Affected individuals usually have low muscle tone and feeding difficulties during infancy. Later in
childhood, however, obsessive eating and obesity develop. Other features commonly seen in individuals
with this condition include short stature, mental retardation, small hands and feet, small,
underdeveloped genitals, characteristic facial features, and decreased sensitivity to pain. Behavior
problems, such as skin picking, stubbornness, temper tantrums, obsessive-compulsiveness, and, in
some, psychosis can also be present (18). See also Chapter 9.
ANGELMAN SYNDROME
Approximately 60–80% of cases of Angelman syndrome are caused by the same microdeletion
found in the majority of cases of Prader Willi syndrome, except that the deletion occurs on the maternally
derived 15, and there are, in fact, differences at the molecular (DNA) level. The clinical features
most commonly found in affected individuals include severe mental retardation, inappropriate excessive
fits of laughter, “jerky” limb movements, characteristic facial features, sleep abnormalities, and
seizures (18). Imprinting also plays a role in this disorder. See Chapter 9.
WILLIAMS SYNDROME
Williams syndrome is the result of a microdeletion on chromosome 7 at the q11.23 locus and
involves the elastin (ELN) gene. The condition is usually sporadic, but, as with the 22q microdeletion
syndrome, can also follow an autosomal dominant pattern of inheritance. As infants, affected individuals
tend to experience failure to thrive, gastrointestinal complications, delayed milestones, and
delayed speech. The rate of growth is slow and mental retardation, characteristic facial features,
cardiovascular defects, renal abnormalities, and joint problems are often present. One of the most
interesting features of Williams syndrome is the unique, characteristic personality. Affected individuals
tend to be extremely friendly and talkative. Certain behavior problems, such as a generalized
anxiety and sleep difficulties, can be encountered (18). See Chapter 9.