Transcript module-3-genetics-an-dd

GENETICS, FETAL
DEVELOPMENT, FIRST DAYS
OF LIFE, AND
DEVELOPMENTAL DISABILITIES
MODULE 2
SEPTEMBER 12TH
BASIC GRAPHIC OF GENETICS (CELL,
NUCLEUS, CHROMOSOME, DNA, GENE)
AND TERMS TO UNDERSTAND
GENETIC DISORDERS
• The nucleus of a single cell contains chromosomes.
• Chromosomes contain the genetic code or deoxyribonucleic acid (DNA)
• DNA is organized into hundreds of units of heredity (genes) in each chromosome.
• Genes are responsible for the human physical attributes and biological functioning.
• Within the single cell system a defect may result in a genetic disorder
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Addition of a chromosome (Down Syndrome)
Loss of a chromosome (Turner Syndrome)
Loss or deletion of a part of a chromosome (Cri-Du-Chat Syndrome)
Microdeletions of genes within a chromosome (velocardiofacial syndrome)
Defect within a single gene (phenylketonuria)
Altered expression of the gene (Rett Syndrome)
What are chromosome abnormalities?
• There are many types of chromosome abnormalities. However, they can be organized into two basic groups:
numerical abnormalities and structural abnormalities.
• Numerical Abnormalities: When an individual is missing one of the chromosomes from a pair, the condition is
called monosomy. When an individual has more than two chromosomes instead of a pair, the condition is called
trisomy.
• Structural Abnormalities: A chromosome's structure can be altered in several ways.
o Deletions: A portion of the chromosome is missing or deleted.
o Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material.
o Translocations: A portion of one chromosome is transferred to another chromosome. There are two main
types of translocation. In a reciprocal translocation, segments from two different chromosomes have been
exchanged. In a Robertsonian translocation, an entire chromosome has attached to another at the
centromere.
o Inversions: A portion of the chromosome has broken off, turned upside down, and reattached. As a result,
the genetic material is inverted.
o Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or
without loss of genetic material.
HOW OFTEN DO CHROMOSOMAL
ABNORMALITIES OCCUR?
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25% of eggs and 3-4% of sperm will have an extra or missing chromosome.
1% of eggs and 5% of sperm will have a structural chromosome abnormality.
10-15% of all conceptions will have a chromosomal abnormality.
Approximately 95% of fetuses with chromosomal abnormalities do not make it to
term. Many are lost before pregnancy is recognized.
• Chromosome abnormalities can be inherited from a parent (such as a
translocation) or be "de novo" (new to the individual). This is why, when a child is
found to have an abnormality, chromosome studies are often performed on the
parents.
HOW DO CHROMOSOME ABNORMALITIES
HAPPEN?
• Chromosome abnormalities usually occur when there is an error in cell division. There are two kinds of cell
division, mitosis and meiosis.
• Mitosis results in two cells that are duplicates of the original cell. One cell with 46 chromosomes divides and
becomes two cells with 46 chromosomes each. This kind of cell division occurs throughout the body, except in the
reproductive organs. This is the way most of the cells that make up our body are made and replaced.
• Meiosis results in cells with half the number of chromosomes, 23, instead of the normal 46. This is the type of
cell division that occurs in the reproductive organs, resulting in the eggs and sperm.
• In both processes, the correct number of chromosomes is supposed to end up in the resulting cells. However,
errors in cell division can result in cells with too few or too many copies of a chromosome. Errors can also occur
when the chromosomes are being duplicated.
• Other factors that can increase the risk of chromosome abnormalities are:
• Maternal Age: Women are born with all the eggs they will ever have. Some researchers believe that errors
can crop up in the eggs' genetic material as they age. Older women are at higher risk of giving birth to babies
with chromosome abnormalities than younger women. Because men produce new sperm throughout their lives,
paternal age does not increase risk of chromosome abnormalities.
• Environment: Although there is no conclusive evidence that specific environmental factors cause chromosome
abnormalities, it is still possible that the environment may play a role in the occurrence of genetic errors.
CHROMOSOMES
• 46 chromosomes in each human cell
• Organized into 23 pairs
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Normally one pair from the mother and one pair from the father
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22 are autosomes
1 is sex chromosomes (E.g., X, Y)
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XX is female
XY is male
CELL DIVISION
• Prenatal development is accomplished by cell division.
• Unequal division of chromosomes during cell division can
adversely affect development.
DOWN SYNDROME
• Graphic of the chromosomes of a boy with Down
Syndrome. The arrow points to the extra chromosome 21.
DOWN SYNDROME
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Down syndrome is caused by a person having three copies of chromosome 21 instead of two copies. This
is why Down syndrome is also referred to by the name Trisomy 21. It is important to understand that all of
the chromosomes of this person are normal.
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Nondisjunction - During cell division to create a germ cell (either sperm or egg), a cell containing
46 chromosomes divides into two germ cells each containing 23 chromosomes. Sometimes this
division does not happen properly and one cell may contain 22 chromosomes and the other may
contain 24 chromosomes. This can happen if the chromosomes do not properly separate and
instead "stick together.“
Three Types of Down Syndrome:
• Trisomy - the extra chromosome 21 comes from either the egg or sperm cell. Between 90% and
Chris Burke, actor “Life Goes On”
95% of all Down syndrome is Standard Trisomy 21.
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Translocation - a piece of chromosome 21 is located on another chromosome such as chromosome
14. The person with Translocation Trisomy 21 will have 46 chromosomes but will have the genetic
material of 47 chromosomes. The person with Translocation Trisomy 21 will exhibit all the same
characteristics of a person with Standard Trisomy 21 since they have three copies of chromosome
21. Translocation occurs between 3% and 5% of cases of Down syndrome.
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Mosaicism - a mix of cells, some containing 46 chromosomes and some containing 47 chromosomes.
This occurs either because: a) The person received 46 chromosomes at fertilization but somewhere
during early cell division the chromosome 21 cell pairs failed to split creating a cell with 47
chromosomes and a cell with 45 chromosomes. The cell with 45 chromosomes can not survive but
the cell with 47 chromosomes will continue to divide. All cells that come from this cell will contain 47
chromosomes. b) The person received 47 chromosomes at fertilization but later during cell division
the extra chromosome is lost. Mosaicism occurs in 2% to 5% of cases of Down syndrome. A person
with Mosaic Down syndrome may exhibit all, some, or none of the characteristics of Down
syndrome depending on the percent of cells carrying the extra chromosome and where these cells
are located.
Read: http://www.downsyn.com/joomla/index.php/questions-articles/what-is-down-syndrome
TURNER SYNDROME
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Graphic of Turner Syndrome genetics
showing the X chromosome deleted in
girls/women.
“If you've watched 'NCIS: Los Angeles', a
famous CSB series, the chances are you
already know Lydia Susanna Hunter.
However, you may not know already that this
American TV, film, and stage actress is
among the list of celebrities with Turner
syndrome. She started her career as a singer,
but made her Hollywood debut with an
appearance in the Popeye film version. She
has won 13 awards, including the 2012 Teen
Choice Award and the 1984 Oscar Award
for the Best Supporting Actress.”
(http://www.newhealthadvisor.com/Celebriti
es-with-Turner-Syndrome.html)
TURNER SYNDROME
• WHAT IS TURNER SYNDROME? Turner syndrome (TS) is a non-inherited chromosomal condition that occurs in
approximately 1 in 2,000 live-born females. Typically, an individual’s cells contain 46 chromosomes (23 pairs),
which hold all the genes that tell the body how to function. One of these pairs, the “sex chromosomes,”
determine a person’s gender. Turner syndrome results when one of the two female X chromosomes is completely
or partially deleted. There are approximately 70,000 women, girls and babies affected.
WHAT ARE THE FEATURES OF TURNER SYNDROME? Turner syndrome is a variable condition and not all girls and women will exhibit
all of the possible features. The most common feature, which is shared among almost everyone with TS, is short stature. Other
characteristics may include: • Delayed puberty • Heart defects • Puffy hands and feet (especially at birth) • Infertility due to
nonfunctional ovaries • Kidney, thyroid and liver concerns • Hearing loss • Recurring ear infections • Learning difficulties (i.e.
math) with normal intelligence • Scoliosis • Social difficulties Plus common traits such as: • Short stature (under 5 feet) •
Wide/short neck sometimes with excess skin (“neck webbing”) • Many moles • Low-set ears • Receding lower jaw • Low
hairline at the back of the neck • Arms that turn out more at the elbows
HOW IS TURNER SYNDROME DIAGNOSED? Turner syndrome can be diagnosed throughout the lifespan. It
can be discovered prenatally with an amniocentesis, or chorionic villus sampling (CVS), or into adulthood
with a blood test called a karyotype, examining the cells to detect missing or damaged chromosomes. It is
believed that half of all diagnoses are pre-teens or older. Prenatal diagnosis is generally due to the
discovery of a cystic hygroma(fluid filled sac on the back of the neck), generalized edema, or congenital
heart defect. Incidental diagnosis may also result from chorionic villus sampling or amniocentesis testing
performed due to advanced maternal age, chromosomal abnormality in a previous pregnancy, or
abnormal triple-screen testing results. There is no correlation between a TS diagnosis and advanced
maternal age. Childhood diagnosis usually occurs when a girl falls significantly below her peers in
height/growth. Recurrent ear infections and hearing loss may gives clues as well.
CRI-DU-CHAT (“CAT CRY”)
• Part but not all of a chromosome is lost
• Visible chromosomal deletion
• Graphic shows visible chromosomal deletion in Cri-du-Chat
syndrome with Chromosome 5p Deletion.
CRI-DU-CHAT
• “Cri-du-chat (cat's cry) syndrome, also known as 5p- (5p minus)
syndrome, is a chromosomal condition that results when a piece of
chromosome 5 is missing. Infants with this condition often have a highpitched cry that sounds like that of a cat. The disorder is
characterized by intellectual disability and delayed development,
small head size (microcephaly), low birth weight, and weak muscle
tone (hypotonia) in infancy. Affected individuals also have distinctive
facial features, including widely set eyes (hypertelorism), low-set
ears, a small jaw, and a rounded face. Some children with cri-du-chat
syndrome are born with a heart defect.”
(https://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome)
22Q11.2 DELETION SYNDROME
• Microdeletion syndrome
• 22q11.2 deletion syndrome has been termed a microdeletion syndrome.
• 22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost
any part of the body. The features of this syndrome vary widely, even among affected
members of the same family. Common signs and symptoms include heart abnormalities that
are often present from birth, an opening in the roof of the mouth (a cleft palate), and
distinctive facial features. People with 22q11.2 deletion syndrome often experience
recurrent infections caused by problems with the immune system, and some develop
autoimmune disorders such as rheumatoid arthritis and Graves disease in which the immune
system attacks the body's own tissues and organs. Affected individuals may also have
breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result
in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties,
gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild
short stature and, less frequently, abnormalities of the spinal bones.
• Many children with 22q11.2 deletion syndrome have developmental delays, including
delayed growth and speech development, and learning disabilities. Later in life, they are at
an increased risk of developing mental illnesses such as schizophrenia, depression, anxiety,
and bipolar disorder. Additionally, affected children are more likely than children
without 22q11.2 deletion syndrome to have attention deficit hyperactivity disorder (ADHD)
and developmental conditions such as autism spectrum disorders that affect communication
and social interaction.
GENES
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Genetic disorders may also be the result of a single gene.
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Point Mutations
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Phenylketonuria (PKU)
• hat is phenylketonuria (PKU)?
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Phenylketonuria (PKU) is an inherited disorder of metabolism that causes an increase in the blood of a chemical
known as phenylalanine. Phenylalanine comes from a person's diet and is used by the body to make proteins.
Phenylalanine is found in all food proteins and in some artificial sweeteners. Without dietary treatment,
phenylalanine can build up to harmful levels in the body, causing mental retardation and other serious problems.
•
Women who have high levels of phenylalanine during pregnancy are at high risk for having babies born with
mental retardation, heart problems, small head size (microcephaly) and developmental delay. This is because the
babies are exposed to their mother's very high levels of phenylalanine before they are born.
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In the United States, PKU occurs in 1 in 10,000 to 1 in 15,000 newborn babies. Newborn screening has been used
to detect PKU since the 1960's. As a result, the severe signs and symptoms of PKU are rarely seen.
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What are the symptoms of PKU?
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Symptoms of PKU range from mild to severe. Severe PKU is called classic PKU. Infants born with classic PKU
appear normal for the first few months after birth. However, without treatment with a low-phenylalanine diet,
these infants will develop mental retardation and behavioral problems. Other common symptoms of untreated
classic PKU include seizures, developmental delay, and autism. Boys and girls who have classic PKU may also have
eczema of the skin and lighter skin and hair than their family members who do not have PKU.
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Babies born with less severe forms of PKU (moderate or mild PKU) may have a milder degree of mental
retardation unless treated with the special diet. If the baby has only a very slight degree of PKU, often called mild
hyperphenylalaninemia, there may be no problems and the special dietary treatment may not be needed.
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Read: https://www.genome.gov/25020037/learning-aboutphenylketonuria/learning-about-phenylketonuria/
GENES
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Insertions
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Spinal Muscular Atrophy (insertion)
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Spinal muscular atrophy is a genetic disorder that affects the control of muscle movement. It is caused by a loss of specialized nerve cells,
called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). The loss of motor neurons leads to
weakness and wasting (atrophy) of muscles used for activities such as crawling, walking, sitting up, and controlling head movement. In severe cases
of spinal muscular atrophy, the muscles used for breathing and swallowing are affected. There are many types of spinal muscular atrophydistinguished by
the pattern of features, severity of muscle weakness, and age when the muscle problems begin.
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Type I spinal muscular atrophy (also called Werdnig-Hoffman disease) is a severe form of the disorder that is evident at birth or within the first few months of
life. Affected infants are developmentally delayed; most are unable to support their head or sit unassisted. Children with this type have breathing and
swallowing problems that may lead to choking or gagging.
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Type II spinal muscular atrophy is characterized by muscle weakness that develops in children between ages 6 and 12 months. Children with type II can sit
without support, although they may need help getting to a seated position. Individuals with this type of spinal muscular atrophy cannot stand or walk unaided.
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Type III spinal muscular atrophy (also called Kugelberg-Welander disease or juvenile type) has milder features that typically develop between early childhood
and adolescence. Individuals with type III spinal muscular atrophy can stand and walk unaided, but walking and climbing stairs may become increasingly
difficult. Many affected individuals will require wheelchair assistance later in life.
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The signs and symptoms of type IV spinal muscular atrophy often occur after age 30. Affected individuals usually experience mild to moderate muscle
weakness, tremor, twitching, or mild breathing problems. Typically, only muscles close to the center of the body (proximal muscles), such as the upper arms
and legs, are affected in type IV spinal muscular atrophy.
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The features of X-linked spinal muscular atrophy appear in infancy and include severe muscle weakness and difficulty breathing. Children with this type often
have joint deformities (contractures) that impair movement. In severe cases, affected infants are born with broken bones. Poor muscle tone before birth may
contribute to the contractures and broken bones seen in these children.
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Spinal muscular atrophy, lower extremity, dominant (SMA-LED) is characterized by leg muscle weakness that is most severe in the thigh muscles
(quadriceps). This weakness begins in infancy or early childhood and progresses slowly. Affected individuals often have a waddling or unsteady walk and
have difficulty rising from a seated position and climbing stairs.
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An adult-onset form of spinal muscular atrophy that begins in early to mid-adulthood affects the proximal muscles and is characterized by muscle cramping
of the limbs and abdomen, weakness in the leg muscles, involuntary muscle contractions, tremors, and a protrusion of the abdomen thought to be related to
muscle weakness. Some affected individuals experience difficulty swallowing and problems with bladder and bowel function.
•
Review description of SMA: https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy
GENES
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Duchenne Muscular Distrophy (Deletion)
• Duchenne muscular dystrophy is the most common fatal genetic disorder diagnosed in
childhood, affecting approximately 1 in every 3,500 live male births (about 20,000 new
cases each year worldwide). Because the Duchenne gene is found on the X-chromosome, it
primarily affects boys; however, it occurs across all races and cultures.
• Duchenne results in progressive loss of strength and is caused by a mutation in the gene that
encodes for dystrophin. Because dystrophin is absent, the muscle cells are easily damaged.
The progressive muscle weakness leads to serious medical problems, particularly issues
relating to the heart and lungs. Young men with Duchenne typically live into their late
twenties.
• Becker muscular dystrophy, which is less severe than Duchenne, occurs when dystrophin is
manufactured, but not in the normal form or amount.
• Duchenne can be passed from parent to child, but approximately 35% of cases occur
because of a random spontaneous mutation. In other words, it can affect anyone. Although
there are medical treatments that may help slow its progression, there is currently no cure
for Duchenne.
•
(http://www.parentprojectmd.org/site/PageServer?pagename=understand_about)
AUTOSOMAL RECESSIVE
TRAITS/DISORDERS
• Genes come in pairs. One gene in each pair comes from the mother, and the other gene comes
from the father. Recessive inheritance means both genes in a pair must be abnormal to cause
disease. People with only one defective gene in the pair are called carriers. These people are
most often not affected with the condition. However, they can pass the abnormal gene to their
children.
• If you are born to parents who carry the same autosomal recessive change (mutation), you have
a 1 in 4 chance of inheriting the abnormal gene from both parents and developing the disease.
You have a 50% (1 in 2) chance of inheriting one abnormal gene. This would make you a carrier.
• In other words, for a child born to a couple who both carry the gene (but do not have signs of
disease), the expected outcome for each pregnancy is:
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•
•
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A 25% chance that the child is born with two normal genes (normal)
•
(https://medlineplus.gov/ency/article/002052.htm)
A 50% chance that the child is born with one normal and one abnormal gene (carrier, without disease)
A 25% chance that the child is born with two abnormal genes (at risk for the disease)
See graphic next slide
AUTOSOMAL RECESSIVE INHERITANCE
GRAPHIC
AUTOSOMAL DOMINANT
TRAITS/DISORDERS
• “Inheriting a disease, condition, or trait depends on the type of chromosome affected (autosomal or sex
chromosome). It also depends on whether the trait is dominant or recessive.
• A single abnormal gene on one of the first 22 nonsex (autosomal) chromosomes from either parent can
cause an autosomal disorder.
• Dominant inheritance means an abnormal gene from one parent can cause disease, even though the
matching gene from the other parent is normal. The abnormal gene dominates.
• An autosomal dominant disease can also occur as a new condition in a child when neither parent has the
abnormal gene.
• A parent with an autosomal dominant condition has a 50% chance of having a child with the condition.
This is true for each pregnancy. It means that each child's risk for the disease does not depend on whether
their sibling has the disease. Children who do not inherit the abnormal gene will not develop or pass on
the disease.”
• (https://medlineplus.gov/ency/article/002049.htm)
AUTOSOMAL DOMINANT
INHERITANCE GRAPHIC
AUTOSOMAL RECESSIVE DISORDERS
What is autosomal recessive inheritance? Autosomal recessive inheritance means that the gene in question is
located on one of the autosomes. These are numbered pairs of chromosomes, 1 through 22. Autosomes do not
affect an offspring's gender. "Recessive" means that 2 copies of the gene are necessary to have the trait or
disorder. One is inherited from the mother, and 1 from the father. If you have only 1 recessive gene, you are
a "carrier" for the trait or disease, but you do not have any health problems from "carrying" 1 copy of the
gene. Most people do not know they carry a recessive gene for a disease until they have a child with the
disease. It's estimated that all people carry about 5 or more recessive genes that cause genetic diseases or
condition.
Key Terms:
•
Cystic fibrosis: Cystic fibrosis (CF) is a common, inherited, single-gene disorder, in Caucasians. People with CF
produce mucus that is abnormally thick and sticky that can damage body organs. The mucus interrupts the
function of vital organs especially the lungs, and leads to chronic infections. CF also involves the pancreas and
causes decreased absorption of essential nutrients and reproductive system damage.
•
Sickle cell anemia: Sickle cell anemia is another common, inherited, single-gene disorder in African-Americans.
About 1 in 500 African-American babies is born with sickle cell anemia. About 1 in 12 African-American
people carries the gene for this disease. Sickle cell disease involves the red blood cells, or hemoglobin, and
their ability to carry oxygen. Normal hemoglobin cells are smooth, round, and flexible, like the letter "O." They
can easily move through the vessels in our bodies. Sickle cells are stiff and sticky. When they lose their
oxygen, they form into the shape of a sickle, or the letter "C." These sickle cells tend to cluster together and
can't easily move through the blood vessels. The cluster causes a blockage and stops the movement of healthy,
normal, oxygen-carrying blood. This blockage is what causes the painful and damaging complications of sickle
cell disease.
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Tay-Sacks Disease: Tay-Sachs disease is a fatal disorder in children (usually by age 5) that causes a
progressive degeneration of the central nervous system. It is caused by the absence of an enzyme called
hexosaminidase A (or hex A). Without hex A, a fatty substance builds up on the nerve cells in the body,
particularly the brain. The process begins early in pregnancy when the baby is developing. It is not apparent
until several months after the birth. To date, there is no cure for Tay-Sachs. About 1 in 27 persons of European
Ashkenazi Jewish ancestry carries the Tay-Sachs gene.
Read:https://www.urmc.rochester.edu/Encyclopedia/Content.aspx?ContentTypeID=90&ContentID=P02142
AUTOSOMAL DOMINANT DISORDERS
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Neurofibromatosis
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“Neurofibromatoses (NF) are genetic disorders of the nervous system that cause tumors to grow on nerves.
These tumors are benign, which means they are not cancer. NF also can cause abnormalities of skin and
bone. The severity of symptoms varies greatly. “
•
(http://www.marchofdimes.org/baby/neurofibromatoses.aspx#)
• There are two types of neurofibromatosis. This disorder can result in multiple disabilities, orthopedic
impairment, learning disabilities, and other complications.
• Achondroplasia
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“Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means "without
cartilage formation." Cartilage is a tough but flexible tissue that makes up much of the skeleton during early
development. However, in achondroplasia the problem is not in forming cartilage but in converting it to bone
(a process called ossification), particularly in the long bones of the arms and legs. Achondroplasia is similar
to another skeletal disorder called hypochondroplasia, but the featuers of achondroplasia tend to be more
severe.”
•
•
(https://ghr.nlm.nih.gov/condition/achondroplasia)
Students with achondroplasia may receive special education services through 504 plans or IEPs students may
qualify under the category of other health impaired or orthopedic impairment.
X-LINKED DISORDERS (SEX-LINKED)
• “X-linked inheritance means that the gene causing the trait or the disorder is located on the X
chromosome. Females have two X chromosomes; males have one X and one Y. Genes on the X
chromosome can be recessive or dominant. Their expression in females and males is not the
same. Genes on the Y chromosome do not exactly pair up with the genes on the X chromosome. Xlinked recessive genes are expressed in females only if there are two copies of the gene (one on each
X chromosome). However, for males, there needs to be only one copy of an X-linked recessive gene in
order for the trait or disorder to be expressed.”
•
(http://www.chop.edu/conditions-diseases/x-linked-recessive-red-green-color-blindnesshemophilia#.V9RILVe_cbY
• Primarily affect males
•
•
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Males only have one X chromosome
10% of males with intellectual disability are affected by X-Linked conditions
Up to 10% of all known genetic errors which cause intellectual disabilities are located on the X chromosome
• Hemophilia
•
“Hemophilia A. Hemophilia A is a disorder where the blood cannot clot properly due to a deficiency of a clotting
factor called Factor VIII. This results in abnormally heavy bleeding that will not stop, even from a small cut.
People with hemophilia A bruise easily and can have internal bleeding into their joints and muscles. The
occurrence of hemophilia A (Factor VIII deficiency) is around 1 in 4500 live male births. The occurrence of
hemophilia B (Factor IX deficiency) is one in 20,000 live male births. Hemophilia A accounts for most cases.
Treatment is available by infusion of Factor VIII (blood transfusion). Female carriers of the gene may show some
mild signs of Factor VIII deficiency, such as bruising easily or taking longer than usual to stop bleeding when cut.
However, not all female carriers present these symptoms. One-third of all cases are thought to be new mutations
in the family (not inherited from the mother).”
•
(http://www.chop.edu/conditions-diseases/x-linked-recessive-red-green-color-blindnesshemophilia#.V9RILVe_cbY)
MITOCHONDRIAL DISORDERS
• “Mitochondrial diseases result from failures of the mitochondria, specialized compartments present in
every cell of the body except red blood cells. Mitochondria are responsible for creating more than
90% of the energy needed by the body to sustain life and support growth. When they fail, less and
less energy is generated within the cell. Cell injury and even cell death follow. If this process is
repeated throughout the body, whole systems begin to fail, and the life of the person in whom this is
happening is severely compromised. The disease primarily affects children, but adult onset is
becoming more and more common.
• Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver,
skeletal muscles, kidney and the endocrine and respiratory systems.
• Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness
and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver
disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis,
developmental delays and susceptibility to infection”
• (http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934627)
• Gene Therapy (Optional Material – But Take a Quick Look at this Graphic)
• http://www.ohsu.edu/news/media/images/MitochondriaGeneTherapy.jpg
FETAL DEVELOPMENT
•
The table on the following slide illustrates the changes and
development of the fetus.
•
You will notice that development in the first 8-weeks is
significant and there are significant risks of malformations or
birth defects during the earliest period of pregnancy.
•
We will not cover fetal development in this course. However,
understanding critical periods in neonatal development are
illustrated in the table that follows.
FETAL DEVELOPMENT
FETAL DEVELOPMENT
• The information for the following two slides is available
at:
• http://discovery.lifemapsc.com/library/review-ofmedical-embryology/appendix-3-critical-periods-ofhuman-development-sensitivity-to-teratogens
• Additional discussion of these topics is also available.
• Students are not required to visit the site or the additional
information.
FETAL DEVELOPMENT
• Major morphologic abnormalities occur during weeks 3 to 7. However, physiologic defects and minor
morphologic abnormalities do occur from week 8 to term
• Weeks 1 and 2: period of dividing zygote, implantation, and bilaminar embryo
• THE EMBRYO IS NOT NORMALLY SUSCEPTIBLE to teratogens during this period
•
A substance will damage either all or most of the cells at this time, resulting in prenatal death, or the embryo will
survive with few defects, if any
• Week 3
• THIS IS A HIGHLY SENSITIVE PERIOD for the developing heart and central nervous system
•
•
Highly sensitive for the heart from the middle of week 3 to week 6
Highly sensitive period for the central nervous system from the beginning of week 3 through early in week 6
FETAL DEVELOPMENT
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Week 4
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DURING THIS PERIOD, the eyes, ears, arms, and legs begin to develop
•
•
•
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Sensitive period for the eyes is the middle of week 4 to the middle of week 8
Sensitive period for the ears is the middle of week 4 to the middle of week 9
Sensitive period for the arms is the middle of week 4 to the end of week 7
Sensitive period for the legs is the middle of week 4 to the end of week 7
•
Week 6
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THE TEETH are most sensitive between the end of week 6 until the end of week 8
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THE PALATE is most sensitive between the end of week 6 until early in week 9
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Week 7 Forward
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THE EXTERNAL GENITALIA are most sensitive from the middle of week 7 until the end of week 9
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Periods of lesser sensitivity to teratogens
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THE CENTRAL NERVOUS SYSTEM: from early in week 6 to term
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THE HEART: from late in week 6 to the end of week 8
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THE ARMS: during week 8
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THE EYES: middle of week 8 to term
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THE LEGS: during week 8
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THE TEETH: during weeks 9 and 10
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THE PALATE: during week 9
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THE EXTERNAL GENITALIA: late in week 9 to term
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THE EAR: middle of week 9 to the end of week 16
ENVIRONMENTAL TOXICANTS AND
NEUROCOGNITIVE DEVELOPMENT
• Exposure to toxicants at different developmental periods may lead to different and adverse effects for
the developing fetus. The previous illustration demonstrated periods of development and risk periods for
specific adverse events. Exposure to the following toxicants increase risk for the fetus.
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Lead
Mercury
Arsenic
Alcohol
Polychlorinated Biphenyls
Pesticides
Endocrine Disrupting chemicals
Environmental Tobacco Smoke
• Understand how a woman can prevent birth defects: https://www.acog.org/Patients/FAQs/ReducingRisks-of-Birth-Defects
BIRTH DEFECTS AND PRENATAL
DIAGNOSIS
• Prior to and during pregnancy many birth defects can be
predicted or identified. There are many prenatal
diagnostic tests which can identify potential concerns for
the developing child. Learn more about a number of
these tests through reading
• http://www.merckmanuals.com/home/women-s-healthissues/detection-of-genetic-disorders/prenatal-diagnostic-testing
NEWBORN SCREENING
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Immediately following birth a number of newborn screenings are
required, these vary from state to state. Screenings can detect
disorders and diseases. Additionally, hearing screenings can detect
hearing loss at the youngest of ages.
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Screenings may include:
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Endocrine Disorders
Infectious Diseases
Immune Disorders
Metabolic Disorders
Hearing Screening
NEWBORN SCREENING
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Read about newborn screening from the March of Dimes
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http://www.marchofdimes.org/baby/newborn-screening-testsfor-your-baby.aspx
Hearing Screening
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Watch a brief video of a newborn hearing screening
• https://www.youtube.com/watch?v=QvrBogzziXA
THE FIRST WEEKS OF LIFE
• We will conclude this lesson with a discussion of a number
critical issues which may occur for a newborn which may
result in disabilities.
THE FIRST WEEKS OF LIFE
• One of the first “tests” of a
newborn is the APGAR. This
scoring system indicates the
condition of a newborn and is
usually conducted at 1 and 5
minutes after birth. Newborns
with initial poor outcomes may
also have a 10 minute score.
The APGAR is used as a tool to
communicate a newborn’s
status and changing status
immediately after birth.
THE FIRST WEEKS OF LIFE
• A poor APGAR score may be indicative of complications
which may occur in the first weeks of an infant’s life.
• We will review a number of complications which may
occur in this stage of development. Many of these
complications lead to disabilities.
THE FIRST WEEKS OF LIFE
• Persistent Pulmonary Hypertension - strain to heart from hypoxia
and high blood pressure in the lungs – heart failure
• Read:
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http://www.nationwidechildrens.org/persistent-pulmonaryhypertension-of-the-newborn
• Watch
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https://www.youtube.com/watch?v=bJjHHGLmtLU
THE FIRST WEEKS OF LIFE
• Hypoxic Ischemic Encephalopathy: HYPOXIC (LACK OF OXYGEN) ISCHEMIC (RESTRICTING
BLOODFLOW) ENCEPHALOPATHY (AFFECTING THE BRAIN).
• When the brain is deprived of oxygen, brain cells are injured. Some may recover, some may die. The
most common causes of oxygen deprivation to the brain are low levels of oxygen in the blood or a
reduced flow of oxygen to the brain. This can happen in a variety of ways prior to birth, during the
birth process, after birth, and during childhood. Different alternate diagnoses include perinatal
encephalopathy, perinatal asphyxia, neonatal encephalopathy or birth asphyxia.
• There are two stages of injury with HIE: The first stage happens immediately after the initial
oxygen deprivation. The second occurs as normal oxygenated blood flow resumes to the brain.
This is called “reperfusion injury” and occurs as toxins are released from the damaged cells.
• What causes HIE?
• HIE has many causes, including placental insufficiency, uterine rupture, placental abruption, true
umbilical knots, cord compression, maternal blood clotting disorders, fetal maternal hemorrhage,
extremely low maternal blood pressure, trauma during delivery, placental blood clots, shoulder
dystocia, cord prolapse, aneurysm rupture, cardiac arrest and near SIDS events.
• Read: http://www.hopeforhie.org/whatishie
THE FIRST WEEKS OF LIFE
• Neonatal Seizures
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Neonatal seizures may be clinically observed (physical features of seizures) or
be observed only through an EEG.
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Physical features of seizures may include lip or tongue movement, ocular
movements, blinking, apnea (stop breathing) with possible low heart rate.
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Neonatal seizures can result in negative outcomes for an infant if untreated.
Watch:
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https://www.youtube.com/watch?v=Igj1HBT6oCQ
THE FIRST WEEKS OF LIFE
• What is hypoglycemia in a newborn baby? Hypoglycemia is when the level of
sugar (glucose) in the blood is too low. Glucose is the main source of fuel for the brain and the
body. In a newborn baby, low blood sugar can happen for many reasons. It can cause problems
such as shakiness, blue tint to the skin, and breathing and feeding problems.
• What are the symptoms of hypoglycemia in a newborn baby? Signs of low blood sugar may
not be obvious in newborn babies. The most common signs include:
• Shakiness
• Blue tint to skin and lips (cyanosis)
• Stopping breathing (apnea)
• Low body temperature (hypothermia)
• Floppy muscles (poor muscle tone)
• Not interested in feeding
• Lack of movement and energy (lethargy)
• Seizures
• Serious Brain Injury
Read:https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=90&contentid=P01961
FIRST WEEKS OF LIFE
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“Neonatal stroke
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A stroke is a sudden stoppage or decrease in the flow of blood in the brain, severe enough that it causes damage to the brain. There are two types of stroke:
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Ischemic and hemorrhagic
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Ischemic stroke is when the blood flow to the brain is diminished, usually because of a clot, called a thrombus, in one of the blood vessels in the brain. There are two types of ischemic
stroke that occur in children, especially newborns:
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sinovenous thrombosis, where there is a clot in one of the veins in the brain, and
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arterial ischemic stroke, where the clot is in an artery in the brain.
Hemorrhagic stroke is when a blood vessel in or near the brain ruptures, causing bleeding in the brain.
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The newborn brain is "plastic," and therefore it is more able to recover after stroke than an adult brain. The nerve cells in the newborn
brain are still forming connections, and this makes it easier for the baby to transfer important functions to other parts of the brain. For
example, if the stroke occurred in the part of the brain that controls speech, as the baby gets older, he might be able to transfer control
of this function to the other side of the brain. Because of the plasticity of the newborn brain, a newborn may have a significant stroke and
still be neurodevelopmentally normal.
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With that said, there are a number of common complications that can arise from stroke in newborns. Cerebral palsy is the most common
complication. Epilepsy, language problems, cognitive or behavioural problems, headache disorders, and seizure disorders can all emerge
as a result of newborn stroke. These conditions require special care over the long term, to ensure the best possible quality of life for the
child.”
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“http://www.aboutkidshealth.ca/En/HealthAZ/ConditionsandDiseases/BrainandNervousSystemDisorders/Pages/Stroke-in-newborns.aspx)
THE FIRST WEEKS OF LIFE
• Neonatal Sepsis
• Read:
• http://www.merckmanuals.com/home/children-s-healthissues/problems-in-newborns/sepsis-in-the-newborn
PREMATURE BABIES
• 13% of pregnancies result in premature birth
• Read:
• http://www.marchofdimes.org/complications/prematurebabies.aspx
PREMATURE INFANTS
• Cause of Premature Births
• C-Section, Multiples, substance abuse, low socioeconomic
factors, maternal educational level, maternal infection,
adolescent pregnancies, placental bleeding, preeclampsia,
smoking
PREMATURE INFANTS
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Complications of being born before 37 weeks
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Apnea. This is a pause in breathing for 20 seconds or more. Premature babies sometimes have apnea. It may happen
together with a slow heart rate.
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Respiratory distress syndrome (RDS). This is a breathing problem most common in babies born before 34 weeks of
pregnancy. Babies with RDS don’t have a protein called surfactant that keeps small air sacs in the lungs from collapsing.
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Intraventricular hemorrhage (IVH). This is bleeding in the brain. It usually happens near the ventricles in the center of the
brain. A ventricles is a space in the brain that’s filled with fluid.
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Patent ductus arteriosis (PDA). This is a heart problem that happens in the connection (called the ductus ateriosus)
between two major blood vessels near the heart. If the ductus doesn’t close properly after birth, a baby can have
breathing problems or heart failure. Heart failure is when the heart can’t pump enough blood.
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Necrotizing enterocolitis (NEC). This is a problem with a baby’s intestines. It can cause feeding problems, a swollen belly
and diarrhea. It sometimes happens 2 to 3 weeks after a premature birth.
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Retinopathy of prematurity (ROP). This is an abnormal growth of blood vessels in the eye. ROP can result in vision loss.
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Jaundice. Observed as yellowing of eyes and skin. The liver may not be fully developed.
• Anemia. Lung condition which may develop in premature infants. BPD may cause fluid in the lungs and scarring and lung
damage.
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Infections. Babies may have difficulty fighting off germs/infections as their immune systems are not fully formed.
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Auditory Toxicity. Premature infants may require support of medicines which maintain life. Many of these medicines are
damaging to the auditory (ear) system and can result in a range of hearing loss and deafness.
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Each of the above complications can result in a range of disabilities