30 10 2014 Chromosomal Anomalies Lecture 2 Dr

30. 10. 2014 Chromosomal Anomalies (Lecture 2) Dr. Archana Rani Associate Professor Department of Anatomy KGMU UP, Lucknow

Trisomy of Sex Chromosomes • Klinefelter syndrome • Triple X syndrome • Double Ysyndrome

Klinefelter Syndrome • Chromosome complement: 47, XXY • Phenotype: Male • Incidence: 1: 1000

Features of Klinefelter Syndrome • Tall stature; thin build; long lower limbs • Testicular atrophy • Female pattern of pubic hair • High pitched voice • Infertility (aspermatogenesis) • Gynaecomastia • Low level of intelligence • Serum testosterone levels low to normal • FSH and LH levels very high • Sex chromatin positive

Klinefelter syndrome: Karyotype

Klinefelter Syndrome

Triple X Syndrome (Superfemale) • Chromosome complement: 47, XXX • Phenotype: Female • Incidence: 1: 1000

Features of Triple X Syndrome • Normal in appearance • Difficulty in speech, learning and emotional responses • Mild mental retardation in 15 -25% cases • Two sex chromatin Barr bodies • Infertility • • • Wide-set eyes Amenorrhoea Expressionless face Enamel hypoplasia Deficient language skills • Delayed development of motor skills

Superfemale: Karyotype

Superfemale

Double Y Syndrome • Chromosome complement: 47, XYY • Phenotype: Male • Incidence: 1: 1000

Features of Double Y Syndrome • Normal in appearance • Tall stature • Aggressive behaviour • Problems in development motor and language

Monosomies of Chromosomes • Presence of only one member of a chromosome pair in a karyotype • More detrimental than equivalent trisomy • Can involve autosomes or sex chromosomes • Usually abort spontaneously • Monosomy of X chromosome results in XO condition called Turner syndrome

Turner Syndrome • Chromosome complement: 45, XO • Phenotype: Female • Incidence: 1: 5000 -8000

Features of Turner Syndrome • Short statured female • Sexual infantilism with primary amenorrhoea and sterility • Short, webbed neck • Prominent ears with defective hearing • Small mandible • Defective vision

Features of Turner Syndrome • • Epicanthal folds Low posterior hair line Cubitus valgus Broad chest with widely spaced nipples Cardiovascular anomalies Hyperconvex finger nails Pigmented nevi Sex chromatin negative

Turner Syndrome: Karyotype

Turner Syndrome

Structural Chromosomal Abnormalities • Results from chromosome breakage • Followed by reconstitution in an abnormal combination • Breaks in any chromosome may be induced by various factors

Structural Chromosomal Abnormalities • Deletion (Deficiency) • Inversion • Translocation • Isochromosome • Ring Chromosome

Deletion • Loss of a (generally small) segment of chromosome A B C D E F G A B D E F G C

Deletion • Arise through spontaneous breakage – some chromosomes have fragile spots – radiation, UV, chemicals, viruses may increase breakage

Deletion • May arise through unequal crossing over A B C D E F G x A B C D E G Deletion C D A B E F G C D E F F G Duplication

Deletions in Humans • Cri-du-chat syndrome – Micro deletion of chromosome 5 • Di-George syndrome – Micro deletion of chromosome 22 • Schizophrenia & Obsessive Compulsive Disorder – Micro deletion of chromosome 22 associated • Angelman syndrome – Micro deletion of chromosome 15 • Prader-Willi syndrome – Micro deletion of chromosome 15

Cri-du-chat syndrome • • • 1 st autosomal deletion described Characteristic cat-like cry, which disappears with age Microcephaly Severe mental retardation Congenital heart disease Hypertelorism (widely separated eyes) Low birth weight and poor growth Severe cognitive, speech, and motor delay Behavioral problems Excessive drooling

Cri-du-chat syndrome

Prader-Willi and Angelman Syndromes Prader-Willi Syndrome • Lack of muscle tone in newborn • Poor swallowing reflex • As adult - gross obesity • Mean I. Q. ~ 50 • Microdeletion of 15 Angelman Syndrome • Developmentally delayed • Jerky movements • Stiff, fixed smile • Uncontrolled laughter • Abnormal E. E. G. , epilepsy • Microdeletion of 15

Inversion • 180 o reversal of chromosome segment A B C D E F G H I J K D I J K 180 O A B C H G F E

Inversion • Produced through breakage and reassociation of chromosome D E C A B F G

Inversion • Produced through breakage and reassociation of chromosome D E C A B F G

Types of Inversion Paracentric Pericentric

Translocation • Exchange of segments between non. F homologous chromosomes E L M D N O C B A P Q

Translocation A B C Q O P N D M E L F

Isochromosome • Centromere of the chromosome divides transversely instead of longitudinally • One arm is missing and the other arm duplicated

Ring Chromosome • Occurs due to loss of both the ends of a chromosome • The broken ends rejoin to form a chromosome • Rare anomaly ring-like

Robertsonian Changes • Fusion two chromosomes join to form one • Fission one chromosome splits to form two

REFERENCES 1. Essentials of Anatomy for Dentistry Students, 1 st Edition. 2. Langman’s Medical Embryology, 11 th Edition. 3. Human Embryology, 5 th Edition.

MCQs 1. Klinefelter syndrome is associated with chromosome complement: a) 47, XXX b) 47, XXY c) 47, XYY d) 47, YYY

MCQs 2. Testicular atrophy is associated with: a) Triple X syndrome b) Double Y syndrome c) Turner syndrome d) Klinefelter syndrome

MCQs 3. Sex chromatin negative is a characteristic feature of: a) Triple X syndrome b) Down syndrome c) Turner syndrome d) Klinefelter syndrome

MCQs 4. All of the following are trisomy of sex chromosomes except: a) Turner syndrome b) Klinefelter syndrome c) Triple X syndrome d) Double Y syndrome

MCQs 5. Partial deletion of short arm of chromosome 5 is a feature of: a) Angelman syndrome b) Prader -Willi syndrome c) Cri-du-chat syndrome d) All of the above