Trisomy 21

Down Syndrome

Named by Langston Downs, 1866

Most common chromosomal abnormality

Brushfield spots in eyes

Round head, small skull

flat nose, upward slanting eyes, protruding tongue

impulsive behavior, slow learning, poor judgement

congenital heart defects, gastrointestinal abnormalities

instability of bones at the top of the neck

Edwards Syndrome

Trisomy 18

Low Birth Weight, small abnormally shaped head

clenched fists with overlapping fingers

heart defects, often die in first month

high muscle tone, seizures, brain defects

extreme malformations of head and face

Patau Syndrome

Trisomy 13

Severe mental deficiency

Holoprosencephaly - prosencephalon does not divide (one lobed brain)

rocker-bottom feet

polydactyly

facial clefting

severe heart defects

Klinefelter Syndrome

XXY

1 in 1000 men

Dr. Harry Klinefelter 1942

Small testicles, infertile, testosterone treatment

frustration-based outbursts, developmental delays

pear shaped body, autoimmune diseases

osteoporosis

Turner Syndrome

XO

1 in 3000-5000 females

shield chest, wide-spaced breasts

short stature, turned-out elbows

small jaws

Kleefstra Syndrome

Deletion on Chromosome 9

Heart conditions, dental conditions

unusually small head, widely spaced eyes

nostrils that open on the front

limited speech, protruding jaw

high birth weight and childhood obesity

Cri Du Chat

Chromosome 5 Deletion Syndrome

Dr. Jerome Lejeune in 1963

Small head, round face, small chin

widely set eyes, folds of skin over eyes

small bridge of nose

behavioral problems, severe intellectual disability

heart defects, muscular or skeletal problems

Jacobsen Syndrome

Loss of genetic material on Chromosome 11

long (q) arm missing genes

11q terminal disorder

central nervous system development impaired

impaired intelligence, problems speaking walking standing

compulsive behavior, short attention span

droopy eyelids, epicanthal folds, broad nasal bridge

V-shaped mouth

3 billion bases

99% are the same in all people

Transmission through mother only

mtDNA

37 genes essential for mitochondrial functioning

produce genes used in oxidative phosphorylation

produce tRNAs which help assemble proteins

convert the energy from food into a form used by cells

each cell has hundreds to thousands of mitochondria

they are found in the cytoplasm (fluid)

visible only during cell division

DNA coiled around proteins called histones

one gene is enough

male and female children equally likely to inherit the disorder

found on chromosome pairs 1-22

requires a gene from both mother and father

found on autosomes (chromosomes 1-22)

Angelman's syndrome

deletion of genes on maternally inherited chromosome 15

Harry Angelman discovered in 1965

flat heads, jerky movements, protruding tongues,

bouts of laughter

happy puppet syndrome

ataxia of gait, tremulous movements

happy demeanor, flapping hands

short attention span, frequent laughter/smiling

Absence or lack of expression of 7 genes on

paternal Chromosome 15

life-threatening obesity

low levels of sex hormones

poor muscle tone

no feeling of fullness leading to overeating

short statue, poor motor skills

von Recklinghausen NF

mutation on Chromosome 17 or 22

areas of hyperpigmentation

late childhood: thousands of tumors on and under skin

Mutation on Chromosome 22

tumor form in the nervous system, usually within the skull and spinal canal

Tumors on the 8th cranial nerve (vestibulocochlear) are most common and lead to acoustic neuromas

Causes hearing loss and loss of sense of balance in 20s

Tumors can become cancerous

Defective gene on Chromosome 7

disease of mucus and sweat glands

affects lungs, pancreas, liver, intestines, sinuses,

and sex organs

Sodium ion channels get blocked by disorder

Recessive autosomal disorder

Leads to lung and digestive problems

Transmitted by mothers

1/2 of sons will have disease

1/2 of daughters will be carriers

X-linked blood clotting disease

1/3 of individual develop hemophilia through spontaneous mutation.

Hemophilia A - deficiency in clotting factor VIII

Hemophilia B - Christmas Disease - deficiency in coagulation factor IX

X-linked deficiency of enzyme alpha-galactosidase A

Lipid fat accumulates in various organs of the body.

Sx.: burning sensation in hands,

raised reddish-purple blemishes on the skin,

clusters of wart-like discoloration of the skin (angiokerotomas),

abdominal pain,

visual impairment,

kidney/heart problems

X-linked

course facial features, short stature

enlarged liver and spleen,

intellectual disabilities,

ivory-colored lesions on the upper back and sides of the upper arms,

progressive deafness,

atypical retinitis pigmentosa

skeletal changes

affects the nervous system white matter and adrenal cortex

resembles ADD or hyperactivity,

progressive cognitive impairment,

Loss of vision, hearing, and motor functions

FMR-1 gene on X Chromosome

Place where gene occurs looks like it might break off,

carrier men pass the premutation on to all of their daughters,

6% of intellectually disabled males,

60% have autism,

hand-flapping,

biting, large ears,

thickened nasal bridge,

large head, prominent jaw and testes

X-linked

Progressive, degenerative central nervous system disease

affects the myelin sheaths like all leukodystrophies,

Sate of Zulia, Venezuela, shore of Lake Maricaibo

Huntington's disease, gene of Chromosome 4

Dominant transmission,

St. Vitas Dance

jaw clenching, abnormal movements, slurred speech,

mood swings, depression, difficulty walking,

loss of mental capacity,

death within 15-20 years,

symptoms due to loss of brain neurons,

more repeats in DNA sequence = more symptoms

Genetic mutation HEXA gene

sx. appear at 6 months

development slows

children become deaf, blind, intellectually disabled, paralyzed, and non-responsive

death by age 5

Lack enzyme Hex-A used to break down fatty waste in brain

Most common inherited blood disease in the U. S.

pain, thirst, bloody urination, penis pain, chest pain, rapid heart rate, breathlessness, fatigue

Life threatening:

1. Hemolytic crises - breakdown of red blood cells

2. Aplastic crises - bone marrow fails to produce blood cells

Body cannot process phenylalanine (Phe)

Hospital screening

inherited metabolic disease

causes brain damage

by 12 months symptoms appear

a single-gene disorder (can be autosomal dominant, autosomal recessive, or X-linked)

No gender difference

HPRT enzyme deficiency

X-linked recessive

build up of uric acid results in:

severe gout, poor muscle control, moderate intellectual disability

Other sx.: facial grimacing, involuntary writhing, repetitive movements of arms and legs, self-mutilating behaviors

Death from renal failure in the second decade of life.

Deficiency of the enzyme glucocerebrosidase

Lipid build up in spleen, liver, and bone marrow

Sx.: enlarged liver or spleen, fatigue, easy bruising, impaired blood clotting, bone pain, and fractures.

Cleft spine

Etiology a mystery

Insufficient folic acid seems to play a role

Spina Biffida Occulta - opening in one or more of vertebrae without damage to the spinal cord.

Closed neural tube defects - malformation of fat, bone, or membranes.

Meningocele - meninges pushed out through the opening in the vertebrae in a sac. Spinal cord is intact.

Myelomeningocele - Most severe form. A portion of the spinal cord itself protrudes through the back.

Absence of a major portion of the brain, skull, and scalp.

Brain tissue is often exposed.

Infants usually die at birth.

Syphilis - blindness, intellectual disability, deafness

Toxoplasmosis - spontaneous abortion, premature delivery, intellectual disability, blindness, cerebral palsy

Rubella - eye disorders, heart defects, ear defects, psychomotor retardation, microcephaly, hepatitis

Cytomegalovirus - blindness, intellectual disability, deafness, death

Herpes Simplex - Central nervous system damage

AIDS - growth retardation, microcephaly, flat nose

leading cause of preventable intellectual disability and birth defects

memory, attention span, intellectual, CNS, communication, vision, and/or hearing problems

Thalidomide - deafness, blindness, absence of limbs, intellectual disability

Diethylstilbestrol (DES) - abnormal reproductive system, cervical/vaginal cancer in daughters

Tobacco - small size, breathing problems, growth retardation, lowered resistance to infection.