Chapter 063. Chromosome Disorders (Part 9) pps

Chapter 063. Chromosome Disorders
(Part 9)

Microdeletion Syndromes
The term contiguous gene syndrome refers to genetic disorders that mimic a
combination of single-gene disorders. They result from the deletion of a small
number of tightly clustered genes. Because some are too small to be detected
cytogenetically, they are termed microdeletions. The application of molecular
techniques has led to the identification of at least 18 of these microdeletion
syndromes (Table 63-4). Some of the more common ones include the Wilms'
tumor–aniridia complex (WAGR), Miller Dieker syndrome (MDS), and
velocardiofacial (VCF) syndrome. WAGR is characterized by mental retardation
and involvement of multiple organs, including kidney (Wilm's tumor), eye
(aniridia), and the genitourinary system. The cytogenetic abnormality involves a
deletion of a part of the short arm of chromosome 11 (11p13), which typically is
detectable on well-banded chromosome preparations. In MDS, a disorder
characterized by mental retardation, dysmorphic faces, and lissencephaly, the
deletion involves chromosome 17 (17p13). Using FISH, 17p deletions have been
detected in >90% of patients with MDS as well as in 20% of cases of isolated
lissencephaly.
Table 63-4 Some Commonly Identified Microdeletion and
Microduplication Syndromes
Syndrome Cytogenet
ic Location
Principal
Features
Imprintin
g Effects
Langer-Giedion
syndrome
8q24.1

(del)
Sparse hair,
bulbous nose,
variable mental
retardation
No
WAGR complex 11p13
(del)
Wilms'
tumor, aniridia,
genitourinary
disor
ders, mental
retardation
No
Beckwith- 11p15 Macrosomia, Yes,
Wiedemann syndrome (dup) macroglossia,
omphalocoele
occasionally
associated with
"paternal
uniparental
disomy" (see
text)
Retinoblastoma 13q14.11
(del)
Retinoblasto
ma due to
homozygous loss of
functional RB allele

No
obvious effect,
although
abnormal RB
allele more likely
to be paternal
Prader-Willi
syndrome
15q11-13
(del)
Obesity,
hypogonadism,
mental retardation
Yes,
prototypic
imprinting
disorder (see
text)
Angelman 15q11-13 Ataxic gait With
syndrome (del) Prader-Willi
syndrome,
prototypic
imprinting
disorder (see
text)
α-Thalassemia
and mental retardation
16p13.3
(del)

α-
Thalassemia and
mental retardation,
due to deletion of
distal 16p, including
α-globin locus
No
Smith-Magenis
syndrome
17p11.2
(del)
Brachycephal
y, midface
hypoplasia, mental
retardation
No
Miller-Dieker
syndrome
17p13
(del)
Dysmorphic
facies, lissencephaly

No
Charcot-Marie-
Tooth syndrome type
1A
17p11.2
(dup)
Progressive

neuropathy due to
microduplication
No
DiGeorge
syndrome/velocardiofaci
al syndrome
22q11
(del)
Abnormalities
of third and fourth
branchial arches
No