GENETIC DISESES

Genetic Disoders
A genetic disorder is a disease that is caused by an abnormality in an individual s DNA.
Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or set of chromosomes.
Thee types of genetic diseases
1. genetically determined
2. environmentally determined
3. Both.
up to 20% of pediatric in-patients have genetic abnormality
about 50% of spontaneous abortuses have chromosomal aberration
only mutations that are not lethal are reservoir of genetic diseases
Hereditary = derived from parents
Familial = transmitted in the gametes through generations
Congenital = present at birth (not always genetically determined - e.g. congenital syphilis, toxoplasmosis)

Not all genetical diseases are congenital - e.g. Huntington disease - 3rd to 4th decade of life

Mendelian (monogenic) inheitance
Mutation of 1 gene, mendelian type of inheritance
Today about 5000 diseases
Autosomal dominant.
Familial hypercholesterolemia.
( subgroup of hyperlipoproteinemia)
most frequent mendelian disorder - 1:500
mutation of gene encoding LDL-receptor (70% of plasma cholesterol)
heterozygotes 2-3× elev. of plasma cholesterol levels
homozygotes 5× elevation of plasma cholesterol levels

heterozygotes asymptomatic until adulthood - xanthomas along tendon sheets, coronary AS
homozygotes - xanthomas in childhood, death due to MI by the age of 15Y.
Marfan syndrome
French pediatrician Marfan - 1896 - young girl with typical habitus
abnormal protein fibrillin - secreted by fibroblasts, part of ECM
impairment of collagenous and elastic tissue - decreased firmness of connective tissue
principal clinical manifestations involve thee impotant systems.
Skeletal system
slender, elongated habitus long legs, arms and fingers (arachnodactyly),high, arched palate
hyperextensibility of joints spinal deformities, pectus excavatum, pigeon breast
Ocula changes
dislocation or subluxation of the lens (weakness of suspensory ligaments)
Cardiovascular system
fragmentation of elastic fibers in tunica media - aorta aneurysmal dilatation - aortic dissection - rupture (35-45% of pts.) incompetence (dilatation) - aortic valve,tricuspidal and/or mitral valve - floppy valve.
Ehlers-Danlos syndrome
similar to Marfan syndrome
genetic defect of collagen fibrils - several types - both autosomal dominant and recessive
hyperextensibility of skin, hypermobility of joints.
joint dislocations, vulnerability
rupture of large vessels, colon, cornea.
Autosomal recessive
majority of mendelian disorders only homozygotes are affected, heterozygotes (parents) are only carriers
25% of descendants are affected
if the mutant gene occurs with low frequency - high probability in consanguineous marriages
onset of symptoms often in childhood
frequently enzymatic defect
testing of parents and amnial cells
Cystic fibrosis
1:2000 live births - most common lethal genetic disease in white population
defect in the transport of chloride ions across epithelia - increased absorption of Na+ and water to the blood
widespread defect in the exocrine glands - abnormally viscid mucous secretions
blockage of airways, pancreatic ducts, biliary ducts
Pancreatic abnormalities (85%) - dilatation of ducts, atrophy of exocrine part, fibrosis
Pulmonary lesions - dilatation of bronchioles, mucus retention, repeated inflammation, bronchiectasis, lung abscesses, emphysema and atelectasis (100%), cor pulmonale chronicum
GIT - meconium ileus (newborns) (25%), biliary cirrhosis (2%)
Male genital tract - sterility (obstruction of vas deferens, epididymis, seminal vesicles) (95%)
Clinical symptomatology
recurrent pulmonary infections
pancreatic insufficiency, malabsorption syndrome (large, foul stool), hypovitaminosis A, D, E, K, poor weight gain
high level of sodium in the sweat - "salty" children - mother s diagnosis
death usually in 3. decade due to respiratory failure







Autosomal recessive.
X-linked.