How disabilities come to be …How disabilities come to be …Causes, roots, and beginningsCauses, roots, and beginnings

Reason 1. It’s Genetic!Reason 1. It’s Genetic!

DNA (deoxyribonucleic acid) is a nucleic acid that is the most basic unit of genetic information. Chromosomes are highly organized structures containing DNA in long strands. Most cells in our body (except for mature red blood cells) contain a complete set of 46 chromosomes, or 23 pairs.

DNA (deoxyribonucleic acid) is a nucleic acid that is the most basic unit of genetic information. Chromosomes are highly organized structures containing DNA in long strands. Most cells in our body (except for mature red blood cells) contain a complete set of 46 chromosomes, or 23 pairs.

Chromosomes, etc.

Chromosomes, etc.

The chromosomes are numbered 1-22 (largest to smallest) and the 23rd pair are the sex chromosomes, which determine our gender (two "X" chromosomes = female; one "X" and one "Y"

chromosome = male). We inherit our chromosomes at the time of conception: one set of 23 from our mother and one set of 23 from our father. As we grow from a single cell into a complex human being, our chromosomes are copied into each new cell.

The chromosomes are numbered 1-22 (largest to smallest) and the 23rd pair are the sex chromosomes, which determine our gender (two "X" chromosomes = female; one "X" and one "Y"

chromosome = male). We inherit our chromosomes at the time of conception: one set of 23 from our mother and one set of 23 from our father. As we grow from a single cell into a complex human being, our chromosomes are copied into each new cell.

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GenesGenes

Genes are specific subunits or groups of DNA along the

chromosomes. Just as our chromosomes come in pairs,

so do our genes. Each gene codes for a protein (or

chemical) that has a specific function in the body.

Genes are specific subunits or groups of DNA along the

chromosomes. Just as our chromosomes come in pairs,

so do our genes. Each gene codes for a protein (or

chemical) that has a specific function in the body.

MeiosisMeiosis

Meiosis – theformation of ova and sperm.

During In this process, chromosomal mutations may occur.

Meiosis – theformation of ova and sperm.

During In this process, chromosomal mutations may occur.

Reason 1a. Autosomal dominant inheritance.Reason 1a. Autosomal dominant inheritance.

Autosomal dominant conditions affect males and females equally, and only one gene of the pair needs to be abnormal for the individual to have the condition. Every child of an individual with an autosomal dominant condition has a 50% chance of inheriting the mutation and having the disorder.

Autosomal dominant conditions affect males and females equally, and only one gene of the pair needs to be abnormal for the individual to have the condition. Every child of an individual with an autosomal dominant condition has a 50% chance of inheriting the mutation and having the disorder.

Autosomal dominantAutosomal dominant

If the AD gene is there, it is expressed. No carriers here.Children have a 50/50 chance of also being affected by the disorder (one parent affected).

If the AD gene is there, it is expressed. No carriers here.Children have a 50/50 chance of also being affected by the disorder (one parent affected).

BOTH parents have dominant gene:

BOTH parents have dominant gene:

Statistically, there is a 25% chance that the child will inherit the two unaffected genes and will be unaffected.

There is a 50% chance that the child will inherit at least one affected gene, and will have the disorder.

There is a 25% chance that the child will inherit both dominant genes, which is usually fatal.

Statistically, there is a 25% chance that the child will inherit the two unaffected genes and will be unaffected.

There is a 50% chance that the child will inherit at least one affected gene, and will have the disorder.

There is a 25% chance that the child will inherit both dominant genes, which is usually fatal.

Examples of AD … Examples of AD … Neurofibromatosis Tuberous Sclerosis Marfan Syndrome Achondroplasia** Osteogenesis Imperfecta (there

are 7 distinct types; Type II is NM)

Noonan syndrome** Cornelia de Lange

syndrome** Apert syndrome** Treacher-Collins syndrome **new mutations originally; AD

inheritance when passed from an affected individual.

Neurofibromatosis Tuberous Sclerosis Marfan Syndrome Achondroplasia** Osteogenesis Imperfecta (there

are 7 distinct types; Type II is NM)

Noonan syndrome** Cornelia de Lange

syndrome** Apert syndrome** Treacher-Collins syndrome **new mutations originally; AD

inheritance when passed from an affected individual.

Reason 1b. Autosomal recessive inheritance.Reason 1b. Autosomal recessive inheritance.

Autosomal recessive conditions affect males and females equally, but both copies of the recessive gene have to be presentfor the individual to have the condition. Autosomal recessive conditions can be passed on when each parent is a "carrier" for the condition, and their offspring have a 25% risk of inheriting the condition. "Carriers" have one abnormal copy of the gene but do not have clinical symptoms and are not at increased risk to develop the condition. A family history of a recessive condition can reveal multiple individuals in a single generation (brothers and sisters) with the condition; in the case of small families, however, there may be only one affected individual.

Autosomal recessive conditions affect males and females equally, but both copies of the recessive gene have to be presentfor the individual to have the condition. Autosomal recessive conditions can be passed on when each parent is a "carrier" for the condition, and their offspring have a 25% risk of inheriting the condition. "Carriers" have one abnormal copy of the gene but do not have clinical symptoms and are not at increased risk to develop the condition. A family history of a recessive condition can reveal multiple individuals in a single generation (brothers and sisters) with the condition; in the case of small families, however, there may be only one affected individual.

Autosomal recessiveAutosomal recessive

Two carrier parents,

statistically 1 unaffected, 2 carriers, and one affected. (25% chance of being affected by the recessive gene)

Two carrier parents,

statistically 1 unaffected, 2 carriers, and one affected. (25% chance of being affected by the recessive gene)

Autosomal recessive – one carrier parent …

Autosomal recessive – one carrier parent …

As indicated, if only ONE parent is a carrier of a recessive trait, then there is no chance for one of the children to be affected; however, a 50% chance of being a carrier.

As indicated, if only ONE parent is a carrier of a recessive trait, then there is no chance for one of the children to be affected; however, a 50% chance of being a carrier.

Autosomal recessive – one affected parent; one non-

carrier:

Autosomal recessive – one affected parent; one non-

carrier: All children will be carriers, since theymust inherit one affected (recessive) gene from the affected parent, but one (dominant) gene from theunaffected parent.

All children will be carriers, since theymust inherit one affected (recessive) gene from the affected parent, but one (dominant) gene from theunaffected parent.

Autosomal recessive: one affected parent; one carrier

parent:

Autosomal recessive: one affected parent; one carrier

parent:With the

carrier parent, the statistics change to a 50% chance of being affected; 50% chance of being a carrier.

With the carrier parent, the statistics change to a 50% chance of being affected; 50% chance of being a carrier.

Examples of AR …Examples of AR … Usher syndrome Retinitis pigmentosa (AR in

20% to 25% of cases; AD in 15% -- 20%; XLR in 10% -- 15%)

Tay-Sachs disease Sickle Cell Anemia Phenylketonuria Batten disease Pendred syndrome Spinal Muscular Atrophy Albinism Torsion Dystonia (or AD)

Usher syndrome Retinitis pigmentosa (AR in

20% to 25% of cases; AD in 15% -- 20%; XLR in 10% -- 15%)

Tay-Sachs disease Sickle Cell Anemia Phenylketonuria Batten disease Pendred syndrome Spinal Muscular Atrophy Albinism Torsion Dystonia (or AD)

Reason 1c. X-Linked Recessive InheritanceReason 1c. X-Linked

Recessive InheritanceMost X-linked conditions occur in males who inherit an abnormal copy of the gene from their mothers. Since males only have one X chromosome, if it carries an abnormal copy of

the gene, they will suffer from the disorder. These mothers carry a copy of the altered gene but are usually unaffected if their other X chromosome has a normal working copy of the gene.

Most X-linked conditions occur in males who inherit an abnormal copy of the gene from their mothers. Since males only have one X chromosome, if it carries an abnormal copy of

the gene, they will suffer from the disorder. These mothers carry a copy of the altered gene but are usually unaffected if their other X chromosome has a normal working copy of the gene.

X-Linked RecessiveX-Linked Recessive

An affected male never transmits the disease to his sons since the X

chromosome is always passed on from mother to son. When the mother carries a copy of a gene for an X-linked disease, the chance of inheriting the altered gene is 1 in 2 in each pregnancy for both boys and girls, but only the male offspring will be affected.

An affected male never transmits the disease to his sons since the X

chromosome is always passed on from mother to son. When the mother carries a copy of a gene for an X-linked disease, the chance of inheriting the altered gene is 1 in 2 in each pregnancy for both boys and girls, but only the male offspring will be affected.

X-linked recessive: affected father:

X-linked recessive: affected father:

In this family, the father is affected by an X-linked (recessive) disorder. The sons inherit the Y chromosome from their father. All daughters inherit a recessive gene, i.e., are healthy carriers.

In this family, the father is affected by an X-linked (recessive) disorder. The sons inherit the Y chromosome from their father. All daughters inherit a recessive gene, i.e., are healthy carriers.

X-linked recessive: carrier mother; affected father:

X-linked recessive: carrier mother; affected father:

If the mother is a carrier (XXa) and the father is affected (XaY), the children will statistically be: (girls: 50% carrier, 50% affected; boys: 50% unaffected; 50% affected)

Mother: X XaFather: Xa

Y

If the mother is a carrier (XXa) and the father is affected (XaY), the children will statistically be: (girls: 50% carrier, 50% affected; boys: 50% unaffected; 50% affected)

Mother: X XaFather: Xa

Y

XXa(carrier girl)

XaXa(affected girl)

XY (unaffected boy)

XaY (affected boy)

X-linked recessive: affected mother (XaXa) and father

(XaY)

X-linked recessive: affected mother (XaXa) and father

(XaY)Mother and father are affected by the

X-linked recessive gene: all children are affected by the recessive gene.

Mother Xa Xa

Father Xa

Y

Mother and father are affected by the X-linked recessive gene: all children are affected by the recessive gene.

Mother Xa Xa

Father Xa

Y

XaXa (affected girl)

XaXa (affected girl)

XaY(affected boy)

XaY (affected boy)

Examples of XLR …Examples of XLR …

Color BlindnessHemophiliaFragile X SyndromeDuchenne Muscular

DystrophySpinal Bulbar

Muscular atrophyNorrie DiseaseMenkes syndrome

Color BlindnessHemophiliaFragile X SyndromeDuchenne Muscular

DystrophySpinal Bulbar

Muscular atrophyNorrie DiseaseMenkes syndrome

Reason 1d: X-linked Dominant InheritanceReason 1d: X-linked

Dominant InheritanceWhen an X-linked gene is said to express dominant inheritance, it means

that asingle dose of the mutant allele will affect the phenotype of the female. A recessive X-linked gene requires two doses of the mutant allele to affect the female phenotype. The following are the hallmarks of X-linked dominant inheritance: ~The trait is never passed from father to son.~All daughters of an affected male and a normal female are affected.

All sons of an affected male and a normal female are normal.~Matings of affected females and normal males produce 1/2 the sons

affected and 1/2 the daughters affected.~Males are usually more severely affected than females. The trait may be lethal in males.~In the general population, females are more likely to be affected than

males, even if the disease is not lethal in males.

When an X-linked gene is said to express dominant inheritance, it means that a

single dose of the mutant allele will affect the phenotype of the female. A recessive X-linked gene requires two doses of the mutant allele to affect the female phenotype. The following are the hallmarks of X-linked dominant inheritance: ~The trait is never passed from father to son.~All daughters of an affected male and a normal female are affected.

All sons of an affected male and a normal female are normal.~Matings of affected females and normal males produce 1/2 the sons

affected and 1/2 the daughters affected.~Males are usually more severely affected than females. The trait may be lethal in males.~In the general population, females are more likely to be affected than

males, even if the disease is not lethal in males.

X-linked dominantX-linked dominant

Offspring of either gender

have a 50/50 chance of inheriting XLD, if the mother is affected. If

the father is affected, the boys will not be

affected, but girls will always.

Offspring of either gender

have a 50/50 chance of inheriting XLD, if the mother is affected. If

the father is affected, the boys will not be

affected, but girls will always.

Examples of XLD …Examples of XLD …

Aicardi syndrome (occasional new mutation)

Charcot-Marie Tooth Disease (type X)

Hypophosphatemic rickets

Rett syndrome

Aicardi syndrome (occasional new mutation)

Charcot-Marie Tooth Disease (type X)

Hypophosphatemic rickets

Rett syndrome

Reason 1e: Sporadic or new mutations

Reason 1e: Sporadic or new mutations

A MUTATION is a sudden, permanent change in DNA.This change has the potential to cause disorders or diseases.A sporadic or new mutation of this sort has no real risk for recurrence, as a general rule, and remember rules are always broken.

A MUTATION is a sudden, permanent change in DNA.This change has the potential to cause disorders or diseases.A sporadic or new mutation of this sort has no real risk for recurrence, as a general rule, and remember rules are always broken.

Examples of Sporadic/New mutation …

Examples of Sporadic/New mutation …

Trisomy 13 (Patau syndrome)

Trisomy 18 (Edwards syndrome)

Trisomy 21 (Down syndrome)

Cri-du-chat syndromePrader-Willi syndromeRubenstein-Taybi

syndrome

Trisomy 13 (Patau syndrome)

Trisomy 18 (Edwards syndrome)

Trisomy 21 (Down syndrome)

Cri-du-chat syndromePrader-Willi syndromeRubenstein-Taybi

syndrome

Here are some syndromes that belong in this category but could be

considered in the X-linked. But they go here, OK?

Here are some syndromes that belong in this category but could be

considered in the X-linked. But they go here, OK?

XXY syndrome (Klinefelter syndrome)

XXX syndromeTurner syndrome

(XO)XYY syndromeAnd other disorders

involving multiple Xs or Ys.

XXY syndrome (Klinefelter syndrome)

XXX syndromeTurner syndrome

(XO)XYY syndromeAnd other disorders

involving multiple Xs or Ys.

Reason 2: MultifactorialReason 2: Multifactorial

Many reasons exist that might actually cause these disorders – some genetic, some environmental, some because of the interplay between the genes and environment. So all of those disorders

go HERE.

Many reasons exist that might actually cause these disorders – some genetic, some environmental, some because of the interplay between the genes and environment. So all of those disorders

go HERE.

Examples of multifactorial:Examples of

multifactorial: Spina Bifida Cancer Cleft palate Osteoporosis Meningitis Congenital heart defects Encephalitis Anencephaly Microcephaly Pyloric Stenosis Hydrocephaly

Spina Bifida Cancer Cleft palate Osteoporosis Meningitis Congenital heart defects Encephalitis Anencephaly Microcephaly Pyloric Stenosis Hydrocephaly

Reason 3: Perinatal incidents

Reason 3: Perinatal incidents

Conditions, complications, incidents, accidents, mistakes, the unfolding of unfortunate events that occur before, during, or immediately following childbirth.

Conditions, complications, incidents, accidents, mistakes, the unfolding of unfortunate events that occur before, during, or immediately following childbirth.

Examples of Perinatal …Examples of Perinatal …

JaundiceCerebral palsyPrematurityRespiratory distress

syndromeFailure to thrive (maybe

…)

Anoxia

JaundiceCerebral palsyPrematurityRespiratory distress

syndromeFailure to thrive (maybe

…)

Anoxia

Reason 4a: TeratogensReason 4a: Teratogens

Agents that cause malformations in a developing embryo. These agents cross the placental barrier and cause or increase the incidence of physical malformations and behavioral and cognitive deficits. Examples are any medication, chemical, infectious disease, or environmental agent that might interfere with the normal development of a fetus; result in the loss of a pregnancy, a birth defect, or a pregnancy complication.

Agents that cause malformations in a developing embryo. These agents cross the placental barrier and cause or increase the incidence of physical malformations and behavioral and cognitive deficits. Examples are any medication, chemical, infectious disease, or environmental agent that might interfere with the normal development of a fetus; result in the loss of a pregnancy, a birth defect, or a pregnancy complication.

Examples of teratogens …Examples of teratogens …

Toxoplasmosis

Fetal Alcohol Syndrome

Cocaine-exposed or addicted

Toxoplasmosis

Fetal Alcohol Syndrome

Cocaine-exposed or addicted

Reason 4b: Maternal conditions

Reason 4b: Maternal conditions

Infections, diseases, or disorders of a mother during pregnancy, sometimes having the potential to injure the unborn child.

Infections, diseases, or disorders of a mother during pregnancy, sometimes having the potential to injure the unborn child.

Examples of Maternal condition:

Examples of Maternal condition:

AIDSHIVHerpesCongenital

rubella syndrome

Cytomegalovirus

AIDSHIVHerpesCongenital

rubella syndrome

Cytomegalovirus

Reason 5: AbuseReason 5: Abuse

The physical or mental injury, sexual abuse, or negligent treatment of a child under the age of 18 by a person who is responsible for the child's welfare. The specific types are

physical abuse, physical neglect, emotional abuse, emotional

neglect, sexual abuse, sexual exploitation, physical endangerment, abandonment, medical and psychological neglect, educational neglect, and improper ethical guidance.

The physical or mental injury, sexual abuse, or negligent treatment of a child under the age of 18 by a person who is responsible for the child's welfare. The specific types are

physical abuse, physical neglect, emotional abuse, emotional

neglect, sexual abuse, sexual exploitation, physical endangerment, abandonment, medical and psychological neglect, educational neglect, and improper ethical guidance.

Examples of Abuse …Examples of Abuse …

Shaken Baby Syndrome

Nonorganic Failure to Thrive

Shaken Baby Syndrome

Nonorganic Failure to Thrive

REASON 6: Accident, Injury, Illness

REASON 6: Accident, Injury, Illness

Many disabilities with long-term consequences are caused by accidents or illness. Some disabilities are directly

the result of the accident or illness; others as a secondary condition.

Many disabilities with long-term consequences are caused by accidents or illness. Some disabilities are directly

the result of the accident or illness; others as a secondary condition.

Reason 7: UnknownReason 7: Unknown

No idea. Well, maybe an idea, but nothing has panned out so far. But still looking. We’ll let you know.

No idea. Well, maybe an idea, but nothing has panned out so far. But still looking. We’ll let you know.

Examples of UNKNOWN …Examples of UNKNOWN …

AutismAmblyopiaSudden Infant

Death SyndromeAsperger

SyndromeDyslexiaADHDEpilepsyScoliosis

AutismAmblyopiaSudden Infant

Death SyndromeAsperger

SyndromeDyslexiaADHDEpilepsyScoliosis