ANTENATAL DISORDERS

Genetic Factors fertilization of ovum by sperm results in the formation of a zygote chromosomes determines the potential physical and mental traits abnormalities of genes or chromosomes may cause congenital defects Patterns of transmission of traits & diseases GENES- units of heredity found in the chromosome & arranged in linear fashion precise position known as LOCUS genes found at given locus are called ALLELLES Homozygous- pair of allelles are identical Heterozygous- when they are different Multifactorial inheritance- combination of genetic & environmental factors Genotype- individual full set of genes Phenotype- outward expression of o manifested as physical, biochemical or physiological Propositus/ Index case- individual member who first brings the family to theattention of investigator

Neurofibromatosis

nerve tissue grows tumors (neurofibromas) that may be benign or may cause serious damage by compressing nerves and other tissues The tumors may cause bumps under the skin, colored spots, skeletal problems, pressure on spinal nerve roots, and other neurological problems.

AUTOSOMAL RECESSIVE INHERITANCE (a)

abN gene causes damage only in the homozygous form Person w/ abN recessive gene appears N (Aa) AbN recessive + N => all offspring N Heterozygote+ heterozygote (Aa + Aa) 25%-homozygous abN (aa) 25%-gene/pheno N (AA) 50%-pheno N,geno abN (Aa)

Examples: o

Adrenogenital syndrome (congenitall adrenal hyperplasia)

AUTOSOMAL DOMINANT INHERITANCE (A)

gene produces damage even in the heterozygous form Abnormal dominant trait + N (Aa) 50%- abN 50%- N sex does not influence occurrence or transmission o

mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands cortisol complete or partial absence of pigment in the skin, hair and eyes due to absence or defect oftyrosinase, a coppercontaining enzyme involved in the production of melanin. due to a defect in the enzyme homogentisate 1,2dioxygenase (EC 1.13.11.5), which participates in the degradation of tyrosine. As a result, a toxic tyrosine byproduct calledhomogentisic acid (or alkapton) accumulates in the blood and is excreted in urine in large amounts reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin. This can cause the formation of abnormal hemoglobin molecules, thus causing anemia,

Albinism

o examples: o Achondroplastic dwarfism absent cartilage formation o caused by a change in the DNA for fibroblast growth factor receptor 3 (FGFR3), which causes an abnormality 6f cartilage formation o typically short in stature with proportionately short arms and legs. They also tend to have a large head, a prominent forehead, and a flattened bridge of the nose. o Diabetes insipidus o characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine o Spherocytosis o an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped (Donut-Shaped), and therefore more prone to hemolysis.

Alkaptonuria black urine disease

Thallasemia major

SEX LINKED INHERITANCE

Transmission of traits thru genes in sex chromosome X- linkage has more clinical significance Like autosomal traits, those determined by genes on x chromosomes may be dominant or recessive Absence of father to son transmission

A. X linked dominant inheritance o Affected males transmit the trait to all daughters but none to their sons o Affected homozygous female (AA) transmit trait to ALL their children o Affected heterozygous female (Aa) transmit to HALF their children of either sex B. X linked recessive inheritance o Inheritance of recessive gene on x chromosome follows a well defined pattern o Expressed by ALL MALES who carry the gene o Females are affected only if homozygous (AA)

Small nose w/ underdeveloped bridge Scrotal tongue th Short hands w/ incurved 5 finger Single palmar crease Poor muscle tone Lax joints nd 1st and 2 toes widely spaced Cardiac & intestinal abnormalities

CHROMOSOMAL ABNORMALITIES Structural Aberrations Translocation-is the most commonly observed structural abN Breakage & exchange of genetic material bet two chromosomes Deletion of chromosomal material producing a partial monosomy result from breakage & loss of segment of genetic material Numerical Aberrations Euploidy- exist when there is a change of whole chromosome sets Aneuploidy- chromosome number is not an exact multiple of haploid ANEUPLOIDY 1. Trisomy 21 Syndrome (Down Syndrome) - First & best known example of autosomal trisomy in man retarded mental & body growth - Bradycephalic head - Upward & outward slant of eyes - Epicanthus skin fold of eyelid covering inner canthus

DELETIONS 2. Trisomy 18 Syndrome (Edwards Syndrome) - 2nd most common autosomal aberration - Failure to thrive - Mental retardation - Malformed low set ears - Small mandible - Flexion deformities - Overlapping of fingers - Hypertonicity - rocker bottom deformities of feet 1. Cri du chat Syndrome (cat cry syndrome) - Cry of affected infant resembles that of a kitten and is char by a high pitched tense phonation - Microcephaly - Moon facies - Mental retardation - Antimongoloid eyes sland downwards - Epicanthal folds - Hypertelorism - Divergent strabismus - Minor skeletal malformation - Congenital heart disease

SEX CHROMOSOME ABNORMALITIES 1. XO syndrome (Turner Syndrome) - 45/X0 chrom constitution - Raised as girls, fail to develop secondary sex characters - Dwarfism - Webbing of the neck - Low set ears - Mature facial appearance - Cubitus valgus - Poorly developed breasts - Infantile external genitals - Edema of extremities - Coarctation of aorta - Mental deficiency

Trisomy 13 Syndrome (Patau Syndrome) - Associated w/ an additional chromosome in D group - Mental retardation - Seizures - Eye defects (anopthalmia/ colobomata) - Cleft lip/palate - Apparent deafness - Polydactyly - Heart defects

2.

Klinefelter Syndrome (XXY) - Char by male phenotype - Mental retardation - Gynecomastia - Infantile genitals - Eunuchoid body proportions - Sterility - Increased FSH in urine

4.

XYY SYNDROME - Abnormal sex chromosome complement - Tendency of individuals w/ the syndrome to commit anti-social acts

CONGENITAL MALFORMATIONS Funny Looking Odd Looking Kid Syndromes Relate to peculiar facial features Stature, physiognomy Skeletal malformations Growth / mental retardation Hypertelorism Low set ears High arched palate Management Clinical hx Gestational hx Physical exam Laboratory exams Genetic counselling MANAGEMENT OF GENETIC DISEASES Control of external environment Regulation of ingested food Modification of internal envt Surgery Genetic engineering Genetic counselling Prenatal genetic diagnosis Alpha-feto protein found to be elevated in amniotic fluid in open neural tube defect Amniography and Fetography-severe lesions like anencephaly are readily identified Ultrasonography-used in the diagnosis of neural tube defects,congenital heart disease,GI and renal abN,erythroblastosis,mutliple preg Amniocentesis - Analysis of chromosomal constitution due to significant risk of cytogenetic abnormality - Determination of fetal sex bec mother is a carrier of sex linked disorder - Assaying specific enzymes bec of possibility of biochemical defect - Clearance when detectable congenital malformation is suspected

3.

Triple X Female (XXX Superfemale) - Appearance is fairly normal - Secondary sex characteristic poorly developed - The more the number X chromosome ,patient has, the more the mental retardation