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19. Microdeletion Syndromes:
Characteristics and Diagnosis
Abstract
Schmickel first defined the Contiguous Gene syndromes in 1986. These are syndromes that involve the deletion of a contiguous stretch of DNA, including multiple genes, on a chromosome. They are also referred to as microdeletion syndromes or segmental aneusomy. These syndromes are clinically recognized with distinct physical, behavioral, and mental characteristics and often involve some individual features that can be inherited in a Mendelian fashion (i.e., lissencephaly, heart defects, etc.). No other type of cytogenetic abnormality has benefited more from the introduction of fluorescence in situ hybridization (FISH) than these syndromes. While some of the abnormalities can be detected cytogenetically, FISH has added dramatically to the detection of these disorders and should be used whenever possible to confirm the deletions (Table 1).
Table 1  Microdeletion Syndromes

Syndrome

Phenotypic features

Cytogenetic location

FISH probes a

Prader-Willi Syndrome

Hypotonia, Hyperphagia, Obesity, Short Stature, Small Hands and Feet, Hypopigmentation, Mental Retardation

15qll-ql3

Commercial (SNRPN)

Angelman Syndrome

Hypotonia, Microcephaly, Ataxic Gait, Inappropriate Laughter, Seizures, Hypopigmentation, Mental Retardation

15qll-ql3

Commercial (D15S10)

Miller-Dieker Syndrome

Type I Lissencephaly, Dysmorphic Facies

17pl3.3

Commercial (D17S379)

Velo-Cardio Facial Syndrome (Del-22q)

Abnormal Facies, Cleft Palate, Thymic Hypoplasia, Hypocalcemia, Heart Defect (Conotruncal Defect)

22qll

Commercial (TUPLE 1)

Langer-Giedion Syndrome

Trichorhinophalangeal Syndrome (Sparse Hair, Bulbous nose, Cone-shaped Phalangeal epiphyses), Multiple Exostoses, Mental Retardation

8q24.1

Investigator

AWTA (WAGR)

Aniridia, Wilms Tumor, Genitourinary Dysplasia, Mental Retardation

11pl3

Investigator

Smith-Magenis Syndrome

Dysmorphic Facial Features, Behavioral Abnormalities, Self Destructive Behavior, Peripheral Neuropathy, Mental Retardation

17p11.2 (FLII, TOP3, SHMT1)

Commercial

Smith-Magenis Syndrome

Dysmorphic Facial Features, Behavioral Abnormalities, Self Destructive Behavior, Peripheral Neuropathy, Mental Retardation

17p11.2 (FLII, TOP3, SHMT1)

Commercial

Williams Syndrome

Dysmorphic Facial Features, Infantile Hypercalcemia, Congenital Heart Disease, Gregarious Personality, Premature Aging of the Skin, Mental Retardation

7qll.23

Commercial (ELN)

Rubinstein-Taybi Syndrome b

Dysmorphic Facial Features, Broad Thumbs and First Toes, Mental Retardation

16pl3.3

Investigator

Alpha-Thalassemia and Mental Retardation (ATR-16)

Dysmorphic Facial Features, Alpha-Thalassemia, Mental Retardation

16pl3.3

Investigator

Alagille Syndrome b

Dysmorphic Facial Features, Chronic Cholestasis, Vertebral Arch Defects, Pulmonic Stenosis

20pll.23-pl2.2

Investigator

Greig-Cephalopoly-syndactyly Syndrome b

Craniosynostosis, Polysyndactyly, Mental Retardation

7pl3

Investigator

Albrights Hereditary Osteodystrophy-Like Syndrome

Short stocky build, Abnormal Facies, Brachymetaphalangism, Seizures, Developmental Delay

2q37

Investigator

1p36 Deletion Syndrome

Hypotonia, Developmental Delay, Growth Abnormalities, Craniofacial Dysmorphism, Minor Cardiac Malformations

1p36

Investigator

Xp22.3 Deletion

X-Linked Ichthyosis, Mental Retardation, Epilepsy, Ocular Albinism, Kallman Syndrome

Xp22.3

Investigator

Xp21 Deletion

Muscular Dystrophy, Glycerol Kinase Deficiency, Congenital Adrenal Hypoplasia, Mental Retardation

Xp21

Investigator

Saethre-Chotzen Syndrome b

Saethre-Chotzen Syndrome, Learning Difficulties

7p21.1

Investigator

Y Chromosome Deletion

Unilateral Cryptorchidism,Idiopathic Infertility

Yql3

Commercial (PCR Primers)

van der Woude Syndrome

Cleft Lip With or Without Cleft Palate; Bilateral Lip Pits; Hypodontia

1q32-lq1

Investigator

Diamond-Blackfan Anemia

Red Blood Cell Hypoplasia, Macrocephalia, Hypotonia and Psychomotor Retardation

19ql3.2

Investigator

NF1 Microdeletion Syndrome b

Neurofibromatosis, Early Age Onset of Cutaneous Neurofibromas, Facial Dysmorphism, Learning Disabilities, Mental Retardation

17qll.2

Investigator

Distal 22q Microdeletion

Hypotonia, Severe Language Delay, Mild Facial Dysmorphism

22ql3-22qter

Commercial(D22S39, ARSA)

17pll.2 Duplication

Charcot-Marie-Tooth (CMT) Disease, Developmental Delay

17pll.2

Commercial (FLII, TOP 3, SHMT1)

Cat-Eye Syndrome

Coloboma, Choanal Atresia, Learning Disabilities, Mental Retardation

22qll.2

Investigator

Dicenteric (15)

Seizures, Autism, Mental Retardation, Mild Facial Dysmorphism

15qll-15ql3

Commercial (SNRPN)

a FISH probes are available either from Commercial Companies or through Investigators/Published Articles.
b The occurrences of these syndromes are primarily owing to mutations, not chromosomal deletions.
Affiliation(s): (1) Department of Genetics and Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH
(2) Department of Genetics and Center for Human Genetics Laboratory, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
Series: Methods in Molecular Biology  |  Volume: 204  |  Pub. Date: Sep-13-2002  |  Page Range: 275-290  |  DOI: 10.1385/1-59259-300-3:275
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