Chapter 063. Chromosome Disorders (Part 9) pps

Chromosome Disorders Part 9 Microdeletion Syndromes The term contiguous gene syndrome refers to genetic disorders that mimic a combination of single-gene disorders.. Some of the more

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

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

disorders, 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