Transcript Document

Trisomy 13- Patau syndrome
Mental deficiency;
Severe central nervous system
malformations;
Sloping forehead; malformed ears, scalp
defects;
Microphthalmia;
Bilateral cleft lip and/or palate;
Polydactyly; posterior prominence of the
heels.
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.
Turner syndrome- XO
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
Cri du chat syndrome- terminal
deletion chromosome 5
Fragile X syndrome
1 in 1500 male births
may account for much of the excess of
males in the mentally retarded population
Achondroplasia
Any agent that can produce a congenital anomaly or oncrease the
incidence an anomaly in the population
TERATOGENS
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
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
Principles of teratogenesis
Critical periods of development
Dosage of drug or chemical
Genetic constitution of the embryo
DRUGS
THALIDOMIDE
alcohol
Phenytoin
Viruses
Rubella
Toxoplasma infection
Female hormones
Masculinisation of female external
genitalia due to maternal use of
drug during pregnancy
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
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
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
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 infancy25% have a subsequent mental
physical disability-the remaining
50% have a fair to good outlook
after treatment
Causes of congenital anomalies
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
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
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
Abnormal chromosome structure
Translocation
Deletion
Ring chromosome
A, Reciprocal translocation. B, Terminal deletion. C, Ring chromosome. D,
Duplication. E, Paracentric inversion. F, Isochromosome. G, Robertsonian
translocation..
Gene mutation (gene defect)
8%of 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
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”