Trisomy 13- Patau syndrome

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Trisomy 13- Patau syndrome

• Mental deficiency
• Severe central nervous system malformations
• Sloping forehead malformed ears, scalp defects

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• Microphthalmia
• Bilateral cleft lip and/or palate
• Polydactyly posterior prominence of the heels.

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Trisomy 18- Edwards syndrome

• Mental deficiency
• growth retardation
• prominent occiput short sternum ventricular
  septal defect
• micrognathia
• low-set malformed ears,
• flexed digits,
• hypoplastic nails rocker-bottom feet.

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Turner syndrome- XO
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Klinefelter syndrome- XXY trisomy

• Small testes, hyalinization of seminiferous
  tubules aspermatogenesis
• Often tall with disproportionately long lower
  limbs.
• Intelligence is less than in normal siblings.
• Approximately 40 of these males have gynecomastia

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Cri du chat syndrome- terminal deletion
chromosome 5
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Fragile X syndrome

• 1 in 1500 male births
• may account for much of the excess of males in
  the mentally retarded population

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Achondroplasia
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teratogens

• Any agent that can produce a congenital anomaly
  or oncrease the incidence an anomaly in the
  population

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TERATOLOGY

• Study of causes, mechanisms, and patterns of
  abnormal development
• Basic concept is that certain stages of embryonic
  development are more vulnerable to disruption
  than others

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• Organs and parts of embryo are most sensitive to
  teratogenic agents during periods of rapid
  differentiation
• Possible mechanisms of action include alteration
  in intracellular matrix and fetal environment
• Teratogens probably cause disruption of gene
  activity at any critical stage

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Principles of teratogenesis

• Critical periods of development
• Dosage of drug or chemical
• Genetic constitution of the embryo

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Drugs
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thalidomide
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alcohol
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Phenytoin
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Viruses

• Rubella

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• Toxoplasma infection

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Female hormones

• Masculinisation of female external genitalia due
  to maternal use of drug during pregnancy

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STATISTICS

• 50 of all human conceptions are lost either
  before implantation or soon afterwards
• 15 of recognized pregnancies end in spontaneous
  abortion before 12 weeks gestation
• 80-85 of aborted embryos have gross structural
  abnormalities, varying from complete absence of
  embryo in gestational sac blighted ovum to a
  very distorted body shape, or a specified
  abnormality in a single body system

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STATISTICS

• 20-30 of all perinatal deaths occur as a result
  of a serious structural abnormality
• In 80 of these cases, genetic factors can be
  implicated, with a recurrence rate of 1 or more
• 2-3 of all newborns have at least one major
  abnormality
• 10 newborns have minor abnormalities

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STATISTICS

• Anomalies can be single or multiple, and of minor
  or major clinical significance
• 14 of newborns have single minor anomaly
• Minor anomalies indicate presence of associated
  major anomalies
• Presence of a single umbilical artery is
  associated with cardiovascular or renal anomalies
• 90 of babies with 3 or more minor anomalies also
  have 1 or more major defects

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STATISTICS

• If 2 or more abnormalities are present in a
  newborn infant, there is a 10-20 risk of a
  major malformation
• 25 of newborn babies with a major malformation
  die in early infancy-25 have a subsequent mental
  physical disability-the remaining 50 have a fair
  to good outlook after treatment

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Causes of congenital anomalies
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Brief history

• 1941- 1st well-documented reports of maternal
  rubella infection as a cause of cataracts,
  cardiac defects and deafness in the offspring
• Thalidomide tragedy- thalidomide was widely used
  as a sedative during 1958-1962. Severe limb
  anomalies were seen in babies born to mothers who
  took it in 1st trimester
• 40 of these babies died in early infancy due to
  severe cardiac, renal or GI anomalies

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Genetic factors

• 50-60 of spontaneously aborted fetuses have
  chromosomal abnormalities
• 1/3rd of all congenital anomalies are caused by
  genetic factors
• Autosomes and/ or sex chromosomes can be affected
• Persons with chromosome abnormalities have
  characteristic phenotype- they often look more
  like other similarly affected persons than their
  siblings

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Abnormal chromosome number

• Usually as a result of non disjunction of
  homologous chromosomes or 2 chromatids of a
  chromosome in mitosis or meiosis
• This results in trisomy
• Down syndrome is an example of trisomy affecting
  autosomes
• In Klinefelter syndrome trisomy affects sex
  chromosomes

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Abnormal chromosome structure

• Translocation
• Deletion
• Ring chromosome

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A, Reciprocal translocation. B, Terminal
deletion. C, Ring chromosome. D, Duplication. E,
Paracentric inversion. F, Isochromosome. G,
Robertsonian translocation..
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Gene mutation (gene defect)

• 8of all anomalies
• Loss or change in function of a gene
• Most mutations are deleterious and some are
  lethal
• Environmental agents such as radiation can
  accelerate mutation rate
• Anomalies due to gene mutation are inherited as
  recessive or dominant traits

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Environmental factors

• Teratogens agents that can produce a congenital
  anomaly or increase the incidence of an anomaly
• Environmental factors may stimulate genetic
  conditions when two or more children of normal
  parents are affected
• Not everything that is familial is genetic

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