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    Chromosome Abnormalities and Sex Determination

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    prasadbheem
    This document discusses chromosomal abnormalities and sex determination. It begins by explaining that cells normally contain 23 pairs of chromosomes, including one X chromosome in females and one X and one Y chromosome in males. The Y chromosome contains the SRY gene which determines male sex. It then discusses several chromosomal abnormalities including trisomies 21, 18, 13, Turner syndrome, and Klinefelter syndrome. For each one it provides the incidence, risk factors, clinical presentation, and sometimes a karyotype image. It ends by discussing sex determination in more detail, including pseudoautosomal regions, dosage compensation, and the role of the XIST gene in X-inactivation.

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    Chromosome Abnormalities and Sex Determination

    Uploaded by

    prasadbheem
    134 views43 pages
    This document discusses chromosomal abnormalities and sex determination. It begins by explaining that cells normally contain 23 pairs of chromosomes, including one X chromosome in females and one X and one Y chromosome in males. The Y chromosome contains the SRY gene which determines male sex. It then discusses several chromosomal abnormalities including trisomies 21, 18, 13, Turner syndrome, and Klinefelter syndrome. For each one it provides the incidence, risk factors, clinical presentation, and sometimes a karyotype image. It ends by discussing sex determination in more detail, including pseudoautosomal regions, dosage compensation, and the role of the XIST gene in X-inactivation.

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    presentation on chromosomal abnormalities and sex determination

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    This document discusses chromosomal abnormalities and sex determination. It begins by explaining that cells normally contain 23 pairs of chromosomes, including one X chromosome in females and one X and one Y chromosome in males. The Y chromosome contains the SRY gene which determines male sex. It then discusses several chromosomal abnormalities including trisomies 21, 18, 13, Turner syndrome, and Klinefelter syndrome. For each one it provides the incidence, risk factors, clinical presentation, and sometimes a karyotype image. It ends by discussing sex determination in more detail, including pseudoautosomal regions, dosage compensation, and the role of the XIST gene in X-inactivation.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    134 views43 pages

    Chromosome Abnormalities and Sex Determination

    Uploaded by

    prasadbheem
    This document discusses chromosomal abnormalities and sex determination. It begins by explaining that cells normally contain 23 pairs of chromosomes, including one X chromosome in females and one X and one Y chromosome in males. The Y chromosome contains the SRY gene which determines male sex. It then discusses several chromosomal abnormalities including trisomies 21, 18, 13, Turner syndrome, and Klinefelter syndrome. For each one it provides the incidence, risk factors, clinical presentation, and sometimes a karyotype image. It ends by discussing sex determination in more detail, including pseudoautosomal regions, dosage compensation, and the role of the XIST gene in X-inactivation.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 43

    1.

    Chromosomal aberrations
    2. sex determination
    Dr. Bheem Prasad

    vEach cell (except RBO) contain all of the


    chromosomes from both parents in the
    nucleus
    v23 pairs of chromosomes come from each
    parent
    vAutosome: one of the 22 pairs of
    chromosomes that is not responsible for
    determining the sex of the child
    vSex Chromosome: X and Y chromosomes
    responsible for sex determination
    2

    Chromosomal Defects
    Abnormal Number
    Monosomy: one less than the diploid number (45)
    Trisomy: one more than the diploid number (47)

    Mosaicism: some cells have the correct number of


    chromosomes and some have more or less than the
    correct number of chromosomes
    Abnormal Structure
    Deletion: loss of a chromosomal segment
    Translocation: the occurrence of a chromosomal segment at an
    abnormal site either on another chromosome or in the wrong
    position on the same chromosome
    3

    Trisomy 21
    Incidence

    1 : 650 1000 live births, parental age related


    75 % abort spontaneously
    Sex ratio: 3 males / 2 females
    Most common autosomal chromosomal disorder causing mental
    retardation

    Risk Factors

    maternal age
    Parental carrier of translocation

    Prenatal Testing

    Triple screen (alpha-fetal protein decreased, estriol decreased, betaHCG increased)


    If positive, amnio or CVS may be indicated
    4

    Clinical Presentation
    Size: small, 20% are
    premature
    Skull: short and round with a
    flat occiput, separated sutures
    Eyes: slant upward and
    outward
    Prominent epicanthal fold
    Moon-shaped face
    Brushfields spots
    Cheeks: red
    Palate: narrow and short
    Nose: short with flat bridge

    Tongue: protrudes, tongue


    thrusting
    Skin loose around lateral and
    dorsal aspects of neck
    Hands: fingers are short,
    hands are square, thumbs are
    low set, separated more than
    usual from second finger, 5th
    finger is short and curves
    inward, single/bilateral simean
    crease
    Ears: low-set, posteriorly
    rotated ears

    Clinical Presentation
    Umbilicus: herniated
    Feet: wide space between
    great toe and 2nd toe, deep
    crease between great toe
    and the 2nd toe, flat feet
    Heart: VSD
    Duodenal atresia
    Muscular hypotonia
    Retarded psychomotor
    development
    Hyperlaxity of ligaments

    Velvety, loose
    adhering mottled skin
    in infancy, coarse skin
    in adolescence
    Mouth frequently
    open/frequently open
    mouth
    Visual and/or hearing
    impairment
    6

    Trisomy 21

    Trisomy 18
    Edwards Syndrome, Trisomy E, Trisomy 16
    18
    Caused by an extra chromosome 18

    Normal Karyotype

    Edwards Syndrome (47,XY, +18)

    Trisomy 18
    Incidence
    1 : 6000 8000 live births
    F > M (4 : 1)
    Most die in embryonic or fetal life

    Risk factors
    Increased paternal and maternal age

    Prenatal screening
    Good indicator is if in maternal serum during mid trimester have
    low human chorionic gonadotrophin and low unconjugated
    estriol
    Ultrasound
    If anomalies seen, amnio or CVS may be indicated
    9

    Types of Trisomy 18
    Full Form
    Every cell in the body has 3 chromosome 18 instead of
    2
    Severe form

    Mosaic Form
    Some cells have 3 chromosome 18 and others have 2
    Less severe form

    Partial Form
    In some cells there may be an extra copy of part of
    chromosome 18
    Severity dependent on anomalies
    10

    Clinical Presentation
    Prenatal hx: feeble fetal
    activity, polyhydramnios, small
    placenta, single umbilical
    artery
    Post-dates
    SGA
    Weight: low birth weight in
    term infant
    Weak cry
    Response to sound decreased
    Ears: low set and/or abnormal
    shape

    Mouth: micrognathia,
    microstomia, cleft lip, cleft palate
    Mental retardation
    Heart: VSD, PDA, ASD
    Feet: rocker bottom, big toe
    shortened and dorsiflexed,
    clubfeet
    Crossed legs
    Diastasis recti
    Pectus carinatum
    GU defects: horseshoe kidneys,
    hydronephrosis, polycystic
    kidneys
    11

    Clinical Presentation
    Hands: clenched and with
    flexed fingers (usually where
    index finger overlaps 3rd and
    4th fingers),flexion contraction
    of the two middle digits,
    underdeveloped or absent
    thumb, simian crease, arches
    on seven or more fingers, nails
    underdeveloped
    Syndactyly
    Eyes: ptosis of one or both
    eyelids, epicanthal folds

    Head: abnormally
    prominent occiput,
    microcephaly
    Hernias: umbilical,
    inguinal
    Redundant skin folds
    esp. over the back of
    the neck
    Males: cryptorchidism
    12

    Trisomy 18

    13

    Trisomy 13
    Pataus Syndrome, 13+ Syndrome, 13 15 D
    Syndrome, Trisomy Syndrome
    Caused by an extra chromosome 13

    Normal Karyotype

    Trisomy 13 (47,XX,+13)
    14

    Incidence
    1 : 5000 live births
    Male = Female

    Risk Factors
    Increases with maternal and paternal age
    Increases with increased parity
    Parental carrier of balanced translocation

    Prenatal Screening
    Ultrasound
    If anomalies seen, amnio or CVS may be indicated

    15

    Clinical Presentation
    Severe mental and
    psychomotor retardation
    Ears: malformed, low-set
    Hands: flexion deformities;
    polydactyly, simian crease,
    clenched hands
    Heart: VSD, PDA, ASD,
    rotational anomalies
    (dextrocardia)
    Eyes: microphthalmos,
    colobomas of iris, cataracts,
    retinal dysplasia, close set
    (may fuse into one)

    Nose: broad and flattened


    Mouth: cleft lip and palate
    Hernias: umbilical hernia,
    inguinal hernia
    Kidneys: polycystic
    Skin: cutaneous hemangiomas
    Head: dermal sinus on scalp,
    microcephaly
    Brain: gross defects, grand
    mal seizures, myoclonic jerks,
    seizures, holoprosencephaly

    16

    17

    Turners Syndrome
    Turners Syndrome, Monosomy X, Gonadal Dysgenesis,
    Bonnevie-Ullrich Syndrome, XO Syndrome Is the absence of
    one set of genes from the short arm of one X chromosome

    Normal Karyotype

    Turners Syndrome (45,X)

    18

    Incidence

    1 : 2000-3000 live-born females


    Females only affected
    98% of pregnancies with TS spontaneously abort
    10% of pregnancies that spontaneously abort have TS

    Risk Factors
    Increased paternal age
    Mother with mosaic or deletional Turners Syndrome

    SHOX gene association


    SHOX gene provides instructions for making a protein that
    regulates activity of other genes

    19

    Clinical Presentation
    Short stature; mean birth weight
    2.9 kg; average height: 47
    Webbed neck
    Low posterior hairline
    Micrognathia
    Ears: low-set, sometimes
    malformed, prone to otitis media
    Widely spaced hypoplastic
    nipples on a shield-shaped chest
    Increased carrying angle at the
    elbow

    Heart: coarctation of the


    aorta, aortic vavular stenosis,
    bicuspid aortic valve, aortic
    dissection
    Eye: ptosis, strabismus,
    amblyopia, cataracts,
    epicanthal folds, dry eyes, redgreen color blindness
    Congenital hip dislocation
    Abnormal growth patterns
    Congenital lymphedema of
    hands and feet
    20

    Clinical Presentation
    Absent or retarded
    development of
    secondary sexual
    characteristics that
    normally appear at
    puberty
    Absent menstruation
    Absence of normal
    vaginal moisture
    infertility

    Gonadal dysplasia
    Horseshoe kidney
    Unilateral renal
    agenesis
    Intelligence: not at risk
    for mental retardation,
    better verbal then
    visuospatial abilities
    Broad nasal bridge
    21

    22

    Klinefelter Syndrome

    Incidence = 1/1000
    Usually taller than average
    Disproportionately long limbs
    30-50% gynaecomastia
    Infertility / Azoospermia
    I.Q may be reduced relative to sibs

    Example karyotypes = 47,XXY


    47,XXY/46,XY

    23

    Klinefelter Syndrome
    Phenotype very variable some patients are not
    diagnosed until they try for a family
    Mosaics 47,XXY/46,XY may have milder phenotype
    and may be fertile
    Therefore always carry out mosaicism check as
    infertility is the main clinical problem

    24

    Cri-du-chat
    Syndrome

    25

    Fragile X Syndrome
    Moderate to sever mental retardation
    Speech delay, short attention, hyperactivity
    Poor motor coordination and mouthing
    objects
    Poor socialization, temper tantrum
    Mood disorder (bipolar), schizophrenia

    26

    Fragile X syndrome

    Long protruding ears


    Long face and prominent jaw
    Flattened nasal bridge
    High arch palate
    Macroorchidism
    Genetic is complex, 80% penetration in male
    and 30% penetration in female
    27

    Fragile X syndrome

    28

    Angelman syndrome
    Sever mental retardation
    Inappropriate laughter
    Decrease pigmentation of choroid or iris (pale blue
    eyes)
    Ataxia and jerky eye movement
    Sever speech proplem
    Deletion of b15q11q13, maternal in origin
    Paternal uniparental disomy

    29

    30

    Prader-willi syndrome
    (A fat red faced boy in state of somnolency) Charles
    Diickens
    Early hypotonia
    Obesity
    Short stature as adult
    Almond shaped blue eyes
    Mental retardation (mild to moderate)
    Narrow hands

    31

    Prader Willi Facial Features

    32

    Chromosome abnormalities and maternal age

    % trisomic

    clinically recognized pregnancies


    35
    30
    25
    20
    15
    10
    5
    0
    -20

    20-24

    25-29

    30-34

    35-39

    40+

    maternal age
    33

    Sex determination

    34

    The Y chromosome contains far fewer genes


    than the X chromosome.

    35

    Pseudoautosomal Regions (PARs)


    regions on Y chromosome that share homology
    with regions on the X chromosome
    synapse and recombine with it during meiosis
    Presence of such a pairing region is critical to
    segregation of the X and Y chromosomes during
    male gametogenesis

    36

    Y chromosome
    contains:
    the male-specific
    region of the Y
    (MSY)
    a sex-determining
    region of the Y
    (SRY)

    37

    Testis-determining factor (TDF)


    a protein encoded by a gene in the SRY that
    triggers testes formation.

    The MSY consists of three regions:


    X-transposed region
    X-degenerative region
    ampliconic region
    38

    Dosage Compensation Prevents Excessive


    Expression of X-Linked Genes in Humans and
    Other Mammals
    Dosage compensation balances the dose of X
    chromosome gene expression in females and
    males.

    39

    The inactive X is highly condensed, can be


    observed in stained interphase cells, and are
    referred to as Barr bodies.

    40

    The Lyon hypothesis states that


    X-inactivation occurs randomly in somatic cells.
    This is evident in the calico cat.

    41

    The X-inactivation center (Xic) is active on the


    inactive X.
    It consists of the X-inactive specific transcript
    (XIST) gene.

    42

    THANK YOU
    43

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