Microdeletion Syndromes: Characteristics and Diagnosis

互联网2014-02-13

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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)