LECTURE

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LECTURE 4Learning objectives

1. Sex chromosome disorders
2. Sexual ambiguity
3. Chromosomal instability syndromes

XY
XX
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SEX CHROMOSOME DISEASE

• Common than autosomal
• Better tolerated, mostly recognized at puberty
• Induce subtle, problems in sexual development
  fertility
• Higher of X chromosomes greater the mental
  retardation

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• Man is wise. Woman is otherwise.

Russian saying
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KLINEFELTER SYNDROME

• Karyotypes
• 80 47, XXY
• 15 mosaic, 46, XY/47, XXY
• Rarely, 48, XXXY/49, XXXXY
• Clinical features
• 1850, leading cause of male infertility,
  eunuchoid body habitus, minimal mental
  retardation, failure to develop secondary sexual
  characters, gynecomastia, female distribution of
  hair, atrophic testis, ? FSH and estrogen, ?
  testosterone levels

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• Supernumerary Y chromosome (Y polysomy)
• I in 1000 live births
• Phenotypically normal excessively tall, more
  acne
• Normal intelligence
• Some aggressive / antisocial

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Idiogram
XYY
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• 1 in 3000 female births
• Hypogonadism in phenotypic females - complete or
  partial monosomy of X chromosome
• Only 1 survive till birth
• Diagnosis - 45 , X at birth
• Accelerated loss of oocytes in
  ovary, completed by 2 years
• Menopause before menarche

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TURNER SYNDROME

• KARYOTYPES
• Classic 45, X (57)
• Defective second X chromosome
  (40)
• 46, X, i(Xq)
• 46, XXq
• 46, XXp
• 46, X, r(X)
• Mosaic (3) 45, X /46, XX

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MULTI X SYNDROME

• Karyotype 47, XXX or more
• 1 in 1200 new born females
• Mostly women are normal
• Some have amenorrhea, other have menstrual
  irregularities
• Mental retardation proportion to
  number of X chromosomes

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XXX
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GENDER / SEXUAL ORIENTATION
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Embryology

• Male Wolfian/mesonephric duct
• Female Mullerian/paramesonephric
• TDF on short arm of Y chromosome
• Anti-Mullerian factor by Sertoli cells
• Testosterone by Leydig cells cause
  masculinization of external genitalia

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• Sexual orientation
• Genetic sex
• Gonadal sex
• Ductal sex
• Phenotypic sex
• Sexual ambiguity
• True hermaphrodite
• Pseudohermaphrodite
• Male
• Female

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TRUE HERMAPHRODITE

• Presence of testicular/ ovarian tissues
• Ovotestis or separate ovary / testis
• Genitalia ambiguous / poorly developed
• Karyotype 46, XX (75), translocation
  of Y chromosome mosaic XX / XXY
• Heterogeneous group with two X and complete /
  partial Y chromosomes

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MALE PSEUDOHERMAPHRODITISM

• Karyotype 46, XY
• Normal testis or streak
• Defective virilization of the male embryo
• Ext. genitalia ambiguous in the streak testis
• Phenotypic females in testicular feminization
  syndrome
• androgen insensitivity synd

x
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Eden Atwood
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FEMALE PSEUDOHERMAPHRODITIS
M

• Genetic 46, XX
• Ovaries , internal
  genitalia normal
• Ext genitalia
  ambiguous or virilized
• Excessive androgenic steroids congenital adrenal
  hyperplasia or defect in cortisol synthesis

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CHROMOSOME INSTABILITY
SYNDROMES

• Autosomal recessive excessive, randomly broken
  chromosomes
• Evaluation SCE (sister chromatid exchange) BRDU,
  clastogens , UV
• Bloom's syndrome , Fanconi's anemia , ataxia
  telangiactasia, xeroderma pigmentosum

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Summary
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Thank You