Chromosomal abnormalities

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Chromosomal abnormalities

• Mohammad Khassawneh
• Assistant Professor of Pediatrics

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introduction

• Normal human cells contain 23 pairs of
  chromosomes
• This includes one pair of sex chromosome XX or
  XY
• During cell division we can identify chromosomes
• Lymphocytes incubated for 2-3 days or uncultured
  bone marrow in 4-24 hours

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• Haploid set of 23 chromosomes
• Diploid normal number of 46 chromosomes
• Aneuploidy less than an even multiple of 23
  usually is 45 or 47 and rarely 48,49
• Triploidy 69 chromosomes
• Mosaicism
• Abnormal in deletion and translocation(balanced
  and unbalanced)Balanced

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Incidence

• The earlier the abortion the more likely to be
  chromosomal
• 50 of spontanous abortion are chromosomal
  abnormal
• Mostly triploidy. 45 XO, trisomy 16
• 98 of fetus with turner abort
• Generally 6/1000 the incidence of chromosomal
  abnormalities

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When to suspect it

• Unexplained infertility/ balanced translocation
• Multiple abortion gt2
• Prior case of defective baby

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When to suspect itcontinue

• Presence of congenital anomalies
• 45 have minor single anomalies
• 9 3 minor anomalies
• 1.5 HAVE major anomaly
• 2 or more major anomalies may represent genetic
  syndrome or chromosomal abnormalities(10).

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Down Syndrome

• Incidence 1/700
• 2/3 of down fetus spontaneously abort
• Clinical diagnosis depend on gestalt
• Trisomy 21 in 94 of cases with extra chromosome
  from mother mostly(95)
• Risk correlate with maternal age
• lt25 y/o 1/1600
• gt40 y/0 1/80
• 2 are mosaic

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Other Clinical features

• Hypotonia without weakness
• Clinodactaly protruded tongue,small
  ears,brachycephaly,small up turned nose,
  depressed nasal bridge.
• Mental retardation, socially do better with good
  environment (Happy children)

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Clinical issues

• Cardiac and GI
• Hypothyriodism
• Transient leukemoid reaction
• Alzheimers disease up to 25 over 40 y/o
• Early death relate to cardiac dysfunction

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Trisomy 18

• Incidence 1/8000
• Overlaps with trisomy 13
• Sever Mental retardation
• gt90 dead in 1st year

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Trisomy 18

• Small face with prominant occiput
• Small sternum and pelvis
• Flexion deformity of the finger
• VSD and horseshoe kidney

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triploidy

• Complete extra set of chromosomes
• Mostly miscarriages
• Fetal wastage skeleton more than cephalic, 2
  survive to be recognized
• Large hydatidiform placenta
• VSD, ASD, Syndactaly
• Genital and CNS abnormalities

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Trisomy 13

• Sever developmetal retardation
• Incidence 1/20000
• 90 dead in the 1st year

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Trisomy 13

• Midline brain defect
• Malformed ear
• Microophalmos and coloboma
• Scalp defect

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Turner syndrome

• Most common abnormality in early abortion
• Female, short stature, primary amenorrhea,
  sterility, spares hair and underdeveloped breast
• Neonatal wide spaced nipple, lymphedema , shield
  chest,
• Coarctation of the aorta

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Continue turner syndrome

• Normal IQ scale with difficulty in spatial
  orientation such as map
• Present with short stature or delay sex
  maturation
• Hormonal therapy

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• Mosaisim (15), remove gonads
• Recurrent risk is 1-2
• Noonan syndrom AD, fresh mutation
• Pulmonary stenosis, nl stature, microceph, mental
  retardation

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Klinefelter syndrome

• 20 of aspermic adult male (blocked
  spermatogenesis
• 47 XXY in 80 and mosaic in 20
• IQ is 98 (normal) with mild decrease in verbal IQ
• Scoliosis, decrease libido may improve with
  testesterone, gynecomastia

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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

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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

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Genetic imprinting

• Means as genomes pass through miosis it is
  normal for part of it to change.
• During miosis inactive X chromosome become active
  and changes on fragiloe X gene (imprinting) make
  it malignant

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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

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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

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Chromosomal linked disorder

• Smith Lemli opitz syndrome
• Low cholesterol
• High 7 dehydrocholesterol
• Like trsomy 18
• CHARGE
• Coloboma
• Heart
• Atresia of choanae
• Retarded
• Genitalia hypoplasia
• Ear anomalies
• VATER

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