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 . 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. . 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. 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