Human Genetic Disorders

Human Genetic Disorders

• The following is a presentation of several human genetic disorders. Some of the pictures may be disturbing. Please keep in mind that these photographs are taken to assist the medical field in correctly diagnosing genetic disorders.

• Photos are from Smith’s Recognizable Patterns of Human Malformation, Chromosome Abnormalities, and Genetic Counseling, Genetics In Medicine.

Human Genetic Disorders

• Many of the disorders that will be discussed during this presentation are in extremely low frequency in the population. This means that very few individuals in the world suffer from these disorders.

Human Genetics• Heredity• The passing-down of traits from parent to

child through genes, which are located in chromosomes.

Gene

• Pedigree• A diagram that shows the pattern of

inheritance of a gene in a family.

• Sex-Linked Traits• Traits carried by X or Y chromosome

• Example: Colorblindness .. Carried on X chromosome

genotypes…

iB XX

ii XX

BB XX

YX i

YX B

Why is it more common in males?

Genetic Disorders• Types of Genetic Disorders

• Autosomal Recessive Genetic Disorders

• Autosomal Dominant Genetic Disorders

• Nondisjunction Genetic Disorders

• Sex-Linked Nondisjunction Genetic Disorders

Autosomal Recessive Genetic DisordersCystic

fibrosis GalactosemiaPhenylketonuria

On chromosome 7

(1:3900)

Affects respiratory / digestive sys.

Mutation in gene that affects salt movement, thus produces thick sticky mucous on outside of cell. This mucous clogs airways

On chromosome 12

affects how body breaks down protein.

(1:18000)

prevents liver enzyme (PAH) from breaking down phenylalanine., which builds up in blood & poisons nerve cells in brain.

(1:55000)

On chromosome 9

Affects ability to break down galactose

Lack enzyme called GATL (which converts galactose into glucose). Galactose build up in the blood.

Autosomal DominantGenetic DisordersBreast Cancer Colon CancerHuntington's

On chromosome 17 or 13

(5-10% of patients)

Rarely inherited … but can inherit gene

On chromosome 4

brain disorder that affects a person's ability to think, talk, and move.

(1:30000)

have a high #of CAG triplets (>40). Somehow brain cells accumulate clumps of protein that become toxic. Some patients lose > 25% of their brain cells before they die.

(~80% of patients)

On chromosome 5

Have family history – at greater risk ; risk increases when a relative got it before 50--high-risk, because may have inherited one rare genetic condition: FAP (familial adenomatous polyposis).

Aneuploidy

• Abnormal number of chromosomes• Trisomy disorders are considered major chromosomal

abnormalities that involve the addition of an extra chromosome or part of a chromosome. Most individuals will only have two copies of a single chromosome one that was received from Mom and one received from Dad.

• These disorders are caused by a nondisjunction during the process of meiosis and other factors.

• 1/5 of all conceptions and about 1/2 of all spontaneous abortions have chromosome abnormalities

Nondisjunction• When chromosomes don't separate properly during meiosis. • results in gametes w/ too many or few chromosomes.

Nondisjunction Genetic Disorders

• Downs syndrome/Trisomy 21

• Patau syndrome/Trisomy 13

• Edwards syndrome/Trisomy 18

Trisomy 21 / Down Syndrome

• Individuals have partial or total addition of chromosome number 21

• Symptoms– Mental retardation distinctive eyes– enlarged tongue short stature– enlarged heart low body tone– decreased life expectancysmall ears– Slanted palpebral Fissures Flat face

(1:800)

Trisomy 21

Trisomy 13 – Patau syndrome

• Symptoms– defects of eye, nose,

lip, and forebrain– Polydactyly (more then

5 fingers or toes)– hyperconvex

fingernails (arches down)

• Only 18% survive the first year

• Survivors have severe mental defects

• seizures

(1:10000)

Trisomy 13

Trisomy 18- Edwards syndrome

• Clenched hand• Distinct patterns on the

fingertip• Low Arch Dermal - the

crease on tip the 5th finger is missing.

• 80% die w/in first two months

• Only 10% survive the first year

• Usually feeble (weakness)• Limited capacity for

survival• Resuscitation (artificial

breathing) often performed at birth

• apneic episodes neonatally (stop breathing during sleep)

(1:3000)

Trisomy 18

Trisomy Disorders

• Almost all other trisomy situations result in death of the fetus

• Trisomy means there are 3 chromosomes in one location

Triploidy and Tetraploidy

• 1-2% of all pregnancies

• Scarcely any triploids are born alive

• Arise from double fertilization

Sex linked Nondisjunction Genetic Disorders

• Turner syndrome

• Klinefelter syndrome

• Fragile-X syndrome

Sex Chromosome Abnormalities

• A normal female has two X chromosomes• A normal male has an X and a Y

chromosome• There are several disorders where additional

sex chromosomes are present

Turner Syndrome

• Females with only one X sex chromosomes• Physical Characteristics

– Short stature– Web neck– Infertile– Normal intelligence– Low posterior hairline– broad chest with widely spaced nipples– elevated frequency of renal (kidney) and cardiovascular

anomalies

Turner Syndrome

Klinefelter Syndrome

• XXY• First sex chromosome abnormality to be reported• Tall, thin relatively long legs• appear normal until puberty• Hypogonadism (sex hormones are not released)• Infertile due to undeveloped sex orgnas• significantly reduced IQ

Klinefelter Syndrome

Fragile X Syndrome

• In males the lower portion of the X chromosome appears constricted in a karyotype.

• Moderate mental retardation• Fragile site - chromatin fails to condense during mitosis• Females who carry the trait may also show

symptoms• long face with a prominent jaw, large prominent ears,

high arched palate; flattened nasal bridge; Prominent forehead

Fragile X Syndrome

Fragile x syndrome is like Autism

• Developmental delay, speech delay, short attention span or hyperactivity, mouthing of objects persisting at an age beyond expected, difficulty in disciplining the child, frequent temper tantrums, autistic-like behaviors such as rocking, talking to oneself, spinning, unusual hand movements, difficulty with transitions, preference for being alone, echolalia, poor eye contact; poor motor coordination; history of vomiting, spitting up or colic during infancy; history of self-abusive behavior; hand flapping; drooling persisting beyond expected; increase fighting with others; hand/thumb sucking.

General Human Genetic Disorders

Achondroplasia

• Dwarfism- small stature

• Large head• Skeletal disorders• Narrow nasal passages• Respiratory problems

• 90% of cases are fresh mutations

• Older paternal age is a contributing factor to mutation

Achondroplasia

Marfan Syndrome

• Tall stature with long slim limbs• Low tone muscles• Little subcutaneous or skin fat• 60% scoliosis• Heart disorders (thought that Abraham

Lincoln had this disorder)

Marfan Syndrome

Progeria Syndrome

• Hutchinson-Gilford Progeria Syndrome or premature aging disease.

• Noticeable 18-24 months of age.

• Life expectancy 8-21 years with an average of 14 years

• Research on these individuals are done to help us understand the aging process

Progeria Syndrome

• Aged looking skin• Growth failure• Hip dislocation• Arthritis, joint stiffness• Cardiovascular atherosclerosis disease and stroke,

eventually leading to death. • Enlarged heart and high blood pressure• Not specific to sex or ethnicity

Progeria Syndrome

Taratogens

• Any agent that can produce a malformation or raise the population incidence of a malformation.

• Most known teratogens are infectious agents, radiation or drugs (alcohol, cocaine, Tetracycline and Streptomycin- antibiotic, Anticonvulsants)

FAS (Fetal Alcohol Syndrome)

• Maternal alcohol consumption

• Major cause of mental retardation

• Growth retardation• Skeletal defects• Heart defects

– Flat fultrum– enlarged head– neurological disorders

FAS

Metabolic Disorders

• These disorders are characteristic of a breakdown of a biochemical pathway which can cause minor problems or major problems.

• Several of these disorders

Tay’sachs

• Blindness• Severe mental and

physical deterioration (normal to 6 months).

• A missing enzyme causes progressive nerve cell damage.

• Leading to seizures and paralysis.

• Death in early childhood by 5 years of age.

• Lethal autosomal recessive disorder with high frequency in a specific, genetically isolated population

• first disorder where large scaled screening was performed

Tay’sachs

3-5 year old with advanced TaysachsGoggle.com

Phenylketonuria (PKU)

• Autosomal recessive trait.• Causes severe mental

retardation, skin rashes, irritable behavior, musty body odor.

• Cannot degrade the amino acid phenylalanine which accumulates in body fluids preventing the brain from growing and developing normally.

• 1/10,000 live births

• Colorado performs a mandatory test for all newborns (heal prick)

• A strict non-animal protein diet must be followed (eggs, meat, milk etc.) throughout adolescence and possibly adulthood.

• Blood is monitored for ones whole life.

Phenylketonuria (PKU)

Genomic Imprinting

• The expression of the disease phenotype depends on whether it has been inherited from the father or from the mother.

• Prader-Willi Syndrome vs. Angelman’s Syndrome

Prader-Willi Syndrome

• Obesity• Small hands and feet• Short stature• Mental retardation• Do not produce the chemical

that tells them they are full• Severely over weight• Their crave for food can be so

server that parents have to lock their refrigerators

• Inherited from the mother

Angelman’s Syndrome

• “Happy Puppets” disorder

• Mental Retardation• Can understand

only simple commands

• Inappropriate laughter

This is the end….

Use your knowledge to be compassionate and kind towards

others.