Chromosomal Anomalies (Lecture 2) 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 motor and language development

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

Loss of a (generally small) segment of 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

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

Large deletions will most probably be lethal Smaller deletions may allow survival E. coli: deletions of up to 1% have been observed in living cells D. melanogaster : deletions of up to 0.1% observed

Deletions in Humans Cri-du-chat syndrome Di-George 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

Cri-du-chat syndrome 1st 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 Angelman Syndrome Lack of muscle tone in newborn Poor swallowing reflex As adult - gross obesity Mean I.Q. ~ 50 Microdeletion of 15 Developmentally delayed Jerky movements Stiff, fixed smile Uncontrolled laughter Abnormal E.E.G., epilepsy Microdeletion of 15

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

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

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

May change phenotype through “position effects” Inversion May change phenotype through “position effects” move active genes to sites generally inactive; lose gene function move inactive genes to sites generally active; gain gene function May act to preserve blocks of genes (specific alleles) which function well together

Types of Inversion Paracentric Pericentric

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

Translocation A B C O N M L Q P D E 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 ring-like chromosome Rare anomaly

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

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