IDENTIFY COMMON CONGENITAL ANOMALIES IN INFANTS AND CHILDREN

PRENATAL GENETIC EVALUATION AND COUNSELING ----------------------------------------------

GENETIC SCREENING
SCREENING MAY BE USED IN POPULATION AT RISK FOR A PARTICULAR GENETIC DISORDER ONLY APPROPRIATE WHEN THE NATURAL HISTORY OF THE DISEASE IS UNDERSTOOD THE SCREEING TEST ARE VALID AND RELIABLE SENSITIVITY SPECIFICITY FALSE-POSITIVE AND FALSE NEGATIVE RATES ARE ACCEPTABLE EFFECTIVE THERAPHY IS AVAILABLE JUSTIFY ITS COST

TYPE OF SCREENING

HETEROZYGOTE SCREENING PRESYMPTOMATIC SCREENING PRENATAL DIAGNOSIS NEWBORN SCREENING

Heterozygote secreening
Screening a subceptible population
Ashkenazic jewsTay-Sachs High frequenzy of heterozygotes in blackthalasemia

Screening for person who a carrier for a specific disorder to make informed reproductive choices. Consanguineus mating

Presymptomatic genetic screening

In family history of dominantly inherited disorder
Hutingtons ds Breast cancer Adult polycystic kidney disease

Identifying a definite carrier of the genetic disorder

PRENATAL DIAGNOSIS
Steele and Breg
Amniotic fluid cells could be cultured Fetal karyotip can be demonstrated Pregnant women , on the basis of age Woman under 35 yrs old secreening for:
Cystic fibrosis, DMD Other commond genetic disorder

Only 2% prenatal diagnosis are terminated Because of the fetus has a genetic defect

Indication for prenatal diagnosis

Maternal age over 35 Previous child with chromosome abnornality Structural chromosomal abnormality in one parent Family history of a neural tube defect Family history of genetic defect Fetus is at risk of an identifiable defect X-linked disorder

TERMINATION OF PREGNANCY
LEGAL TERMINATION: WHEN THE FETUS IS FOUND TO BE SERIOUSLY ABNORMAL
CHROMOSOMAL DEFECTS ANATOMICAL ABNORMALITIES

HOTLY DEBATED AS ABORTION

GAMETOGENESIS
Conversion of germ cells into male and female gametes OOGENESIS and SPERMATOGENESIS Male gametspermatozoa: 22+Y Female gametovum:22+X Mitosis, meiosis I , meiosis II and cytodifferentiation

MITOSIS AND MEIOSIS

Morphological changes
Oogenesis Maturation of oocytes begins before birth: primordial germ celloogoniaprimary oocytes+epithelial cellprimordial follicle and rest in prophase of first meiotic division because of oocyte maturation inhibitor Maturation of oocytes continues at puberty Spermatogenesis Maturation of sperm begins at puberty,spermatogonia are transform into spermatozoa

OOGENESIS
OogoniaOosit IOosit IImature Folikel primordialFolikel IFolikel IIFolikel de Graaf Oosit I enter prophase of the first meiotic division This may last 40 or more years and finishes only when the cell begins its final maturation Maturation of oocytes contunies at puberty

SPERMATOGENESIS
Maturation of sperm begins at puberty Spermatogonia transformed into spermatozoa Spermiogenesis: spermatedspermatozoa
Formation of the acrosome Condensation of the nucleus Formation of neck, middle piece, tail Shedding of most of the cytiplasm

CLINICAL CORRELATION
Birth defect and spontaneous abortions
Chromosomal abnormalities Mutations

Non disjunction Mosaicism Translocation Microdeletion/deletion Fragile sites

DNARNAPROTEIN ( CENTRAL DOGMA )

INPAIRMENT OF NUMBER AND STRUCTURE OF CHROMOSOME
INPAIRMENT OF PROTEIN SYNTHESE INCLINATION OR DECLINATION OF PROTEIN SYNTHESE: INPAIRMENT OF FUNCTION

A non disjunction

Translocation

MOSAIC

1 ZIGOT MUTATION

MOSAIC

THE FRAGILE SITE

Down syndrome
Mitotic nondisjunction Unbalance translocation between 21 and 13, 14 or 15 Mosaicism Trisomy 21 Genotip: 46,XY. 46,XX Phenotype:

SIMIAN CREASE

Estimation risk correlated to maternal age

Edward syndrome
nondisjunction: Trisomy 18 Genotype: 46,XY . 46.XX The incidence: 1:5000 newborns and ussually die by age 2 months Phenotype:

Klinefelter syndrome
Nondisjunction of XX homologous 47,XXY / 48, XXXy
Phenotype:

Turner syndrome
Nondisjunction in the male gamete Monosomy for X Structural abnormality of X Genotype: 45,X Phenotype:

Deletion
Micro deletio
Genomic imprinting

Large deletion
Cri-du-chat symdrom: Partial deletion of short arm chr 5 or chromosomal lost

Genomic imprinting
Exhibit differential expression depending on whether the genetic material is inherited from ( mother or father ) Angelman syndrome: partial deletion, inherting the deletion on the maternal chromosome 15 ( 15q11-15q13 ) Fradel willi syndrome:partial deletion, inherting the deletion on the faternal chromosome 15 ( 15q11-15q13 )

Fragile sites
A region of chromosome that demonstrate a propensity to separate naturally or under certain manipulation Consist of CGG repeat The fragile site: long arm of X ( Xq27 ) Phenotype : fragile X syndrome Males are more affected

FRAGILE

X SYNDROME

Karyotype of FXMR showing fragile site at Xq27.3 region

COLOUR BLINDNES