Genetic and Developmental

Diseases
OBJECTIVES/RATIONALE
The effects of genetic diseases have life-long consequences.
Although some genetic and developmental disorders may
first emerge at birth, these disorders may appear at any age.
The student will identify common genetic and
developmental disorders, their important signs and
symptoms and common tests used to diagnose these
disorders.
 I. Mitosis and Meiosis
• A. All cells of normal mature individual
have 46 chromosomes.
• These cells duplicate themselves and
divide to form daughter cells, each with 46
chromosomes
• Process is called mitosis and can occur
with most cells in the body
 I. Mitosis and Meiosis
• B. Germ cells that develop into sperm and
ova undergo a different type of cell
division called meiosis.
• One chromosome from each pair is
passed on to each gamete (sperm or
ovum).
• Each gamete has only 23 chromosomes.
• When an ovum is fertilized with a sperm,
the newly formed individual will have a
combined total of the normal forty-six
chromosomes one half (23), from each
Figure 5-2: Meiosis involves two complete divisional operations forming four
potential sex cells.
 Comparing Mitosis & Meiosis
• Chromosome number-
– Mitosis- identical daughter cells
– Meiosis- daughter cells form haploids (4 cells)
• Chromosome behavior-
– Mitosis- act independently
– Meiosis- pair together until anaphase

Genetic Identity-
Mitosis- identical daughter cells
Meiosis- daughter cells have new assortment
of parental chromosomes
-chromatids (either of the two daughter
strands of a replicated chromosome that are
joined by a single centromere and separate
 II. Autosomal and Sex
Chromosomes
 a. 44 of the 46 chromosomes determine body function -
these are referred to as autosomes
 b. the remaining 2 chromosomes determine sex of
individual
 XX chromosomes = female
 XY chromosomes = male
 It is the male sperm that determines sex of fetus
 c. the sex chromosomes are in every cell of body and are
responsible for directing activity of cell specifically for a
female or for a male
Figure 5-1: Each cell nucleus throughout the body contains the genes, DNA, and
chromosomes that make up the majority of an individual’s genome.
 III. Visualizing Chromosomes
• a. Karyotyping – process to visualize
chromosomes which involves:
• taking picture of cell during mitosis
• arranging chromosome pairs in order
from largest to smallest
• numbering chromosome pairs one
through 23
• b. Sex chromosomes can be evaluated by a
buccal smear - test is performed by
obtaining epithelial cells from buccal
cavity of mouth, staining the cell, and
microscopically observing for X
chromosomes (referred to as Barr bodies)
 III. Visualizing Chromosomes
• c. Barr bodies – visualized when two X
chromosomes are present (female)
• X chromosomes are much larger than Y
chromosomes and carry more genetic
information.
• The X chromosome carries genes for
female characteristics and other genes
essential to life (blood formation,
metabolism activities, immunization)
• The Y chromosome is smaller and only
Figure 5-3: Normal human karyotype. (©Custom Medical Stock Photo.)
 III. Visualizing Chromosomes
• d. chromosomes – made of units of DNA (arranged in a specific order)
• each unit of DNA is called a gene
• each chromosome is made up of thousands of genes located at precise
positions in chromosome
• chromosomes (one from each parent) pair up during fertilization of egg
(alleles)
• this matched gene pair determines heredity (characteristics inherited
from parents)
• besides facial features, hair and eye color, heredity is thought to play a
part in many other processes:
– a. development of plaque in arteries
– b. obesity
– c. alcoholism
– d. some mental illnesses
 IV. Understanding basic
heredity
 A. Genotypes are the genetic pattern of an individual.
 each gene in an allele (matched pair) of genes may be
dominate or recessive.
 Dominate genotypes expressed with capital letter
(example: brown eyes = B
 Recessive genotypes are expressed with smaller
(example: blue eyes = b)
 if alleles in a pair match (BB or bb), they are said
to be homozygous
if alleles do not match (Bb) they are said to be
heterozygous (will only express the phenotype of
dominant gene)
 IV. Understanding basic
heredity
 b. expression of a trait (blue eyes, brown hair, etc.) is
called phenotype.
 c. Homozygous pairs (dominant or recessive) will always
express that trait (BB = brown eyes, bb = blue eyes, etc.)
 d. Heterozygous alleles will express the phenotype (trait)
of dominate gene only. (Bb = brown eyes)
 e. Heterozygous pairs are said to be carriers of recessive
disorders - recessive traits will not be expressed unless
paired with another recessive gene
 V. Abnormalities
 A. may be due to chromosomal, genetic, or environmental
factors, or combination of these
 major chromosomal abnormalities usually lead to spontaneous
abortion of fetus
 chromosomal disorders are usually related to number or
placement of chromosomes
 chromosomes may fail to separate properly during cell division
causing daughter cell to have an extra chromosome while other
daughter cell has no chromosomes.
 Abnormal number or structure of autosomal chromosomes is
usually incompatible with life because these chromosomes carry a
large number of essential genes.
Figure 5-4: Transmission of autosomal dominant disorders. (50% chance for an
affected child).
 V. Abnormalities
• B. The most common autosomal chromosomal
disorder is Down syndrome (mongolism)
• Also called Trisomy 21 syndrome
• Caused by the presence of an extra autosome,
nondisjunction
• Results in mental retardation and shorter life
expectancy
• Characteristic appearance: slanted eyes, extra fold
of skin at upper medial corner of the eye, protrusion
of the tongue, short nose
• Short stature, underdeveloped sex organs
 Cri Du Chat Syndrome
• Cat-like cry
• Caused by deletion of part of the short
arm of chromosome 5
• Results in an abnormally small head with
a deficiency in cerebral brain tissue
• Widely spaced eyes and mental
retardation
 VI. Two ways that people acquire an
abnormal gene
 A. mutation of gene during meiosis
 B. passing abnormal gene from parents (heredity)
 a. genetic disorders are passed to offspring in four different ways:
autosomal dominant, autosomal recessive, sex-linked dominant, and sex-
linked recessive.
 1. Autosomal dominant
 Easily recognized because presence of disorders identifies individuals
with dominant gene
 Line of inheritance is easily followed from one generation to another
 Dominant genes will always be expressed
whether homozygous or hetrozygous
 Example of autosomal dominant disorder:
polydactyly (excessive number of finger or toes)
 Autosomal Dominant Diseases
• Polydactyly-is a congenital physical
anomoly causing extra fingers and toes
• Achondroplasia- dwarfism
• Marfan syndrome- genetic disorder of the
connective tissue; causes long fingers and
limbs; problems with heart and valves
• Familial hypercholesterolemia
Figure 5-5: A 12-year old Achondroplastic dwarf. (Note the disproportion of the
limbs to the trunk, the curvature of the spine, and the prominent buttocks.)
 VI. Two ways that people acquire an
abnormal gene
 2. Autosomal recessive
 Only seen when two recessive genes are paired
 Each parent may be phenotypically normal or without sign of
disorder but is a heterozygous carrier of the disorder
 a. When each parent is heterozygous, chance of offspring
having disorder is one in four
 b. If one parent has the disorder, chances increase to one in
two
 c. If one parent is homozygous dominant, none of offspring
will be affected
 d. These disorders may skip generations before it is paired
with another recessive gene and is expressed
Autosomal Recessive
Figure 5-6: Transmission of recessive disorders (25% chance for an affected child).
 Autosomal Recessive Diseases
• Phenylketonuria
• Galactosemia
• Sickle cell anemia
• Tay-Sachs disease
• Albinism
• Cystic fibrosis
 VI. Two ways that people acquire an
abnormal gene
• 3. sex-linked dominant - these are more rare than recessive disorders
and are easily recognized
• 4. sex-linked recessive
– these disorders are typically carried by females and passed to males
– reason for this: recessive gene disorders on the X chromosome of
female are overridden by dominance of normal gene on other X
chromosome
– in males, the X disorder is expressed because there is no
corresponding gene on the Y chromosome.
– X-linked disorders usually appear every other generation since they
are passed mother to son (mother to son; son to daughters (who
become carriers) - affected male is unable to pass this disorder to
sons because male gives a Y chromosome to sons, not an X.
– example of sex-linked recessive disorder: hemophilia
Figure 5-8: Transmission of sex-linked disorders.
 Sex-Linked Inheritance (cont.)
• Color blindness: inability to distinguish
colors
• Hemophilia: is a rare bleeding disorder in
which your blood doesn't clot normally;
usually passed on from mother to son
• Fragile X syndrome – a break or weakness
on long arm of X chromosome
• Hyperactive behavior
• Large body size
• Large forehead or ears with a prominent jaw
• Large testicles (macro-orchidism) after the beginning of puberty
• Mental retardation
• Tendency to avoid eye contact
 VII. Congenital anomalies
• A. Approximately two percent of all
newborns have congenital anomalies
(birth defects).
• a. 65% of congenital anomalies are
idiopathic (unknown cause)
• b. 20% are genetic
• c. 5% are chromosomal
• d. 10% are environmental (maternal
radiation, infection, drugs, alcohol,
medications
 Congenital Diseases
• Appear at birth or shortly after, but they
are not caused by genetic or chromosomal
abnormalities.
• Congenital defects usually result from
some failure in development during the
embryonic stage, or in the first 2 months
of pregnancy. Therefore, congenital diseases
cannot be transmitted to offspring.
• Ex: spina bifida, cleft lip and cleft palate,
and pyloric stenosis.
 Familial Disease
• Diseases run in families but means of
inheritance are not understood
• Most likely the effects of several genes
working together
• Examples: diabetes, allergies, familial
polyposis
 Sex Anomalies
• Turner syndrome: missing sex
chromosome
• Klinefelter syndrome: extra sex
chromosome
• Hermaphrodite: has both testes and
ovaries
• Pseudohermaphrodite: has either but
remainder of anatomy mixed
Figure 5-10: Karyotype for Turner syndrome (45, XO). (Catherine G. Palmer,
Indiana University)
Turner Syndrome
Figure 5-11: Karyotype for Klinefelter syndrome (47, XXY). (Catherine G. Palmer,
Indiana University)
Klinefelter Syndrome
 VIII. Diagnostic Tests
• A. physical for affected individual
• B. ultrasonography of fetus (determines
malformations of head, internal organs,
extremities)
• C. amniocentesis (amniotic fluid analysis
to determine genetic and chromosomal
disorders after 14 wks gestation); can
detect 200 various genetic diseases
• D. maternal blood analysis to observe
abnormal fetal substances
 Diagnosis of Genetic Diseases
(cont.)
• E. Chorionic villus sampling involves
removing cells from the villi through the
cervix. Chorionic villus sampling
gives embryonic or fetal results (gender
and chromosomal information) earlier in
the pregnancy.
 Genetic Counseling
• A genetic counselor usually begins with a
complete family history of both
prospective parents.
• A complete, detailed family history is
called a pedigree.
• Pedigrees are used to determine the
pattern of inheritance of a genetic disease
within a family.
 Genetic Counseling (cont.)
• When the pedigree is complete, the
genetic counselor can inform prospective
parents of the possibility of having
genetically abnormal offspring, and they
can make an informed decision.
 Gene Therapy
• A procedure that involves identification,
manipulation, and transference of genetic
segments into a host to replace defective
genes and to perform desired genetic
activities.
• The genetic material used is compatible
with human DNA that may be cultured in
a microbe and delivered in a viral package
or by injection.
• Also referred to as genetic engineering.
 IX. Common musculoskeletal
genetic/developmental disorders
• Name: Muscular Dystrophy (MD)
• Description: group of genetically inherited diseases characterized by
degeneration of muscles; most common type is Duchenne’s MD.
• Etiology: genetic
• Manifestations:
• • onset usually between ages of two to five years
• • pelvic and leg muscles usually affected first
• o leads to characteristic waddling gait
• o toe walking
• o lordosis
• o Gower’s maneuver (unusual way of getting up from squatting
position due to weakened pelvic muscles)
• o bulking of muscle mass (esp. gastrocnemius) due to fat and
connective tissue deposits
M.D.
 IX. Common musculoskeletal
genetic/developmental disorders
• Diagnosis:
• Physical exam, muscle biopsy,
electromyography
• Prognosis:
• • no cure for MD—physical therapy, leg
braces are effective in maintaining
mobility and quality of life
• • affected children usually confined to
wheelchair by age nine
• • life expectancy usually in late teens or
early twenties
 IX. Common musculoskeletal
genetic/developmental disorders
• Name: Congenital Hip Dislocation
• Description: abnormality of hip joint resulting in femoral head slipping
out of acetabulum; more common in girls
• Etiology: maternal hormones which relax mother’s pelvic ligaments
during labor, thus relaxing infant joint ligaments
• Manifestations:
• • asymmetrical folds of affected thigh
• • difference in leg length
• • limited abduction of affected leg
• Diagnosis: physical examination and hip joint X-ray
• Treatment:
• • closed reduction (placing femoral head in acetabulum); and
maintaining normal position by use of cast for approximately two to
three months
• • surgical treatment may be required in older children
Congenital Hip Dislocation