| 1. Inherited genetic diseases: | caused by abnormal groups of genes passed down from one generation to the next. Ex. CF, Phenylketonuria, and muscular dystrophy. Spontaneous Genetic mutations are caused by an error in DNA replication leading to a base substitution or an insertion or deletion of one or two base pairs from the DNA. |
| 2. Somatic genetic disease: | caused by the sudden appearance of an abnormal form of a gene in one part of the body. Ex. Cancer. |
| 3. Chromosomal Aberrations: | abnormalities of chromosomal structure. Ex. Down Syndrome. |
| 2. Defects in receptors and
transport systems |
Ex. Hypercholesterolemia: a reduced function of
LDL receptor leads to a inability to transport LDL into the cell. For CF patient there is a impaired CL- transport across sweat glands, lungs and pancreas. |
| 3. Alterations of Proteins: | Ex. Sickle cell Anemia |
| 4. Genetically determined
Adverse reactions to drugs: |
Ex. A person that has a deficiency of the
enzyme
G6P normally is not affected by this, but if you give that person the anti malaria drug primaquine, a severe hemolytic anemia can result. |
| 1. Autosomal recessive: | Both parent have the recessive gene. 1 in 4
chance of having disease, 2 in 4 chance
of carrying the disease, 1 in 4 of being normal. Ex. Of diseases include Sickle cell anemia, CF, Familial hypercholesterolemia |
| 2. Autosomal dominant: | At least one parent is affected.
Can affect both males and females. Every child
has a 1 out of 2 chance of having the disease. Can result from a spontaneous mutation. Ex. Marfan, achondroplasia, Huntington's disease, spinal muscle atrophy. |
| 3. X link recessive: | Almost X link disorders are recessive.
Offspring of carrier mom: for daughters, 1out of 2 are normal,
1 out of 2 are carriers. Males have 1 out of 2 chances to have the disease, 1 out of 2 of being normal. An affected male does not transmit the disease but all daughters are affected. Ex. Muscular dystrophy, hemophilia, Diabetes Insipidus. |
| 4. X link dominant: | Only a few of these.
An affected female will transfer the disease to half her sons and half
her daughters.
An affected male will transfer the disease to all his daughters but none of his sons. Ex. Hypospadius |
Karotype:
The study of chromosomes. Includes the staining of chromosomes
in the metaphase period.
Normal Karyotype: 46 XX or 46 XY
| 1. Trisomy: | 47XX + 21 Ex.
Down Syndrome (.15% of all live births),
Trisomy results in a failure to separate during meiosis.(nondisjunction) A number of Trisomy's do permit a live birth but most die at an early age. Another example is Klinefelter syndrome: XXY these males are sterile, mentally retarded and have a lanky build ( 1 in 1000 births) |
| 2. Monosomy: | 45 XY ?6. Monosomy is the result of Anaphase
lag where during either
meiosis or mitosis, the chromosome lags behind and is left out of the cell nucleus. Ex. Turners syndrome XO. Monosomy generally involves the loss of too much genetic information to permit live birth. |
|
3. Mosaicism: |
When mitotic errors give rise to two populations
of cells in the same
individual. More common in the sex chromosomes. For example, one of the daughter cells receives 3 sex chromosomes while the other only receives one. 45X/47XX in the same patient. |
| 4. Polyploid: | 23X3 = 69, results when 2 sperm fertilize one egg.
Common in still births
or miscarriages. |
| 5. Structure changes in the Chromosome: | Results from breakage followed by loss or
rearrangement of material. Can occur spontaneously or by exposure to environmental mutagens such as chemicals or radiation. |
Structure changes include the following:
1. Deletion: refers to a loss of a portion of a chromosome.
46XY 16p (indicates
loss of arm 16)
2. Translocation: A segment of one chromosome is transferred
to another.
3. Ring chromosome: deletion occurs at both ends and the damaged
ends fuse together.
4. Inversion: Involves 2 breaks within a single chromosome
with re-incorporation
of the inverted segment.
Defined as abnormal development unrelated to genes or chromosomes.
Congenital malformations are divided into 2 categories: Single Primary and Multiple Malformation Syndrome
a. Single Primary defects involves only 1 structure. Some of the most common are
congenital hip dislocation, cleft lip and cardiac septal defects.
Etiology is unknown. Associated with multifactorial inheritance.b. Multiple malformation syndromes: several observed defects have the same known
etiology. Can be caused by chromosomal abnormalities, teratogens, single gene
defects or fresh gene mutations. Except for Down syndrome occurs in 1 every
3000 live births.
Causes:
42% Unknown, 8% Teratogens, 3% Maternal conditions
Teratogen- an agent or factor that causes the production of physical defects
in the
developing embryo.
Three main agents include :
1. Drugs, ex. Thalidomide: causes phocomelia,
anomalies of ears, teeth
Warfarin: causes hypoplasia of nose, shortened digits
Tetracycline: causes enamel dysplasia
2. Maternal condition, ex: Diabetes: causes
CHD
Alcoholism: growth retardation, mental deficiency
3. Intrauterine Infections, ex: Rubella, CMV, Toxoplasmosis
Uterine factors: Severe oligohydramnios
Malformation examples: CHD
Extremities- shape, creases
Facies ? cleft lip
CNS ? spina bifida
Renal ? polycystic kidneys
Goals in evaluating a child with structural defects:
1. making a diagnosis
2. risk counseling for parents
3. plan for child's future development