Marietta M.

Diaz,MD,FPPS,FCNSP

Genetic Factors Differences in constitutional makeup, basically intrinsic in nature Interplay of inherited chromosomes determines the potential physical and mental traits Abnormalities of genes or chromosomes contained in the genetic structure of the individual may cause congenital defects

Patterns of Transmission of Traits and Diseases Homozygous-both members of pair of alleles are identical Heterozygous-when both members of pair of alleles are different Single gene or monogenic- when a trait is caused by only a pair of genes Polygenic or multifactorial-when brought about by several pairs of genes

Genotype-individuals

full set of genes Phenotype-individuals outward expression of these manifested as physical,biochemical or physiological traits Propositus-or index case-the individual member who first brings the family to the attention of the investigator

Autosomal Dominant Inheritance-the gene effects its recognizable trait in the heterozygous form Most persons manifesting an abnormal dominant trait are heterozygous If the individual marries and the mate is normal, the offsprings of such mating, half is abnormal and the other half is normal There is no risk for the normal children to have abnormal children provided the mate is normal Ie achondroplastic dwarfism, osteogenesis imperfecta,spherocytosis,Neurofibromatosis

Autosomal Recessive Inheritance-abnormal gene effects a recognizable trait in the homozygous form A person with abnormal recessive trait appears normal If married to a mate with normal genes all offsprings will appear normal If a heterozygote for the trait marries another heterozygote each of the offspring will have one chance out of four of being homozygous and having the abnormal trait Ie adrenogenital syndrome,deaf mutism,cretinism

Autosomal Intermediate Inheritance Presence of a single abnormal gene determines some degree of abnormality Described as incompletely recessive Ie Thalassemia gene Heterozygote for the gene reveals sign and symptoms of thalassemia minor- mild manifestations and life expectancy is long Homozygote manifests a severe disease where the patient does not live long

Sex Inheritance Males- XY Females-XX Theoretically the chances of having either a boy or girl are half and half 106 boys for every 100 girls Difference is explained by the greater probability of a Y bearing sperm to fertilize the ovum since it has less DNA and is thus lighter and more motile

Sex Linked Inheritance- transmission of traits through sex chromosomes; X linked has more clinical significance Main characteristic-absence of father to son transmissionX chromosome of the father is transmitted to none of his sons but to each of his daughter X-linked dominant trait-affected males transmit the disease to all their daughters but none of their sons; affected females who are heterozygous transmit the condition to half of their children of either sex X-linked recessive trait-expressed by all males who carry the gene but the females are only affected if homozygous; trait is never transmitted directly from father to son but is passed on through his daughters to half of their sons

Multifactorial Inheritance-situation in which the disease is the result of the additive effect of one or more abnormal genes and environmental factors Variations in the expression of genes Skipping of generation- slight abnormality may not be obvious Pleitropy- one gene , several effects- single defect may lead to various abnormalities in fully differentiated structures Genetic heterogeneity-several genes, one effect- mutations at different loci can independently produce the same trait Variable age of onset Environmental effects-manifests the disease only if he encounters certain environmental conditions

Numerical- somatic cells contain an abnormal number of normal chromosomes Aneuploidy-chromosome number is not an exact multiple of the haploid set -addition or subtraction of one or more whole chromosomes leading to either trisomy or monosomy Polyploidy-complete extra set of chromosomes, increasing chromosome number to 69

Structural-result from chromosome breakage or rearrangementtranslocation, ring chromosome, isochromosome or inversion

Trisomy 21- Downs Syndrome Hypotonia Poor moro reflex Hyperflexibility of joints Flat facial profile Upslanting palpebral fissure, low set ears simian crease

Trisomy 18-Edwards Syndrome Failure to thrive Micrognathia (abnormally small jaw) Low set ears Short palpebral fissures Narrow palatal arch Rocker bottom feet Transverse palmar crease Mental retardation

Trisomy 13-Patau Syndrome Moderate microcephaly Cleft lip and palate Malformed ears Scalp defects Polydactyly Rocker bottom feet Cryptorchidism (undescended testes)

Cri-du-chat Syndrome-5 p-syndrome Low birth weight Failure to thrive Hypotonia Hypertelorism Cat cry Epicanthal fold Downward slant of the palpebral fissure Strabismus Low set ears mental retardation

Wolf Hirschorn Syndrome-4 p Syndrome Growth retardation Hypotonia Hypertelorism,promine cleft lip/palate Downturnedfishlike mouth Short upper lip and philtrum Micrognathia

9 p Syndrome Craniosynostosis Upslanting palpebral fissures Short nose Depressed nasal bridge Short neck short distal phalanges

Turner Syndrome-45,X Short stature Neck web Cubitus valgus Lack of secondary sexual characteristics Primary amenorrhea infertility

Klinefelter SyndromeXXYSyndrome Long limbs Underdeveloped genitalia Infertility Sparse body hair Mental retardation

Triple Female Syndrome47,XXX Female Delayed motor development Delayed speech Mild intellectual deficit Normal gonadal function Fertile

History Physical

examination Laboratory examination Computerized data base-POSSUM-pictures of syndromes and undiagnosed malformations Genetic counselling

Controlling

the external environment Regulating ingested food Modifying external environment Removing disease tissues or introducing normal donor tissue Genetic engineering Preventing conception or birth of affected individuals by genetic counselling