GENETICS Flashcards
46XXdel(14)(q23)
female
46 chromosomes
deletion of chromosome 14 on the long arm at band 23
Chromosomes
short vs long arm
contain genetic code for making proteins for cellular structure and enzyme rxns
46 chromosomes: 23 pairs
= 22 autosome pairs
=1 pair sex
Pair of chromatids joined by a centromere
Short arm = P (on the top)
Long arm = Q (on the bottom)
Died bands: the higher numbers further from the centromere
47, XY, +21
male
47 chromosomes
extra 21
TRISOMY 21: DOWNS SYNDROME
Chromosomal Abnormalities
two types
Numerical Abnormalities
Structural Abnormalities
–can be inherited or de-novo
in de novo neither parent has the abnormal gene, it spontaneously occurs
Numerical Abnormalities
Non Disjunction Error:
entire chromosome/ sister chromatids, do not separate to different cells–
occurs most in older cells
occurs during meiosis or mitosis
anueuploidy: ( a condition in which the number of chromosomes in the nucleus of a cell is not an exact multiple of the monoploid number of a particular species.)
monosomy: missing chromosomes
trisomy: extra chromosomes
* downs syndrome, turner syndrome, kleinfelter syndrome
Structural Abnormalities (4)
Deletions: portion of entire chromosome is missing
Duplications: portion of chromosome is duplicated resulting in extra genetic material
Translocations: portion of one chromosome is transferred to another chromosome
Inversions: a portion of the chromosome has broken off and turned upside down and reattached, causing the genetic material to be inverted
Deletions:
portion of entire chromosome is missing
cri cu chat (de novo chromosome 5)
prader will syndrome (de novo paternal deletion chromosome 15)
angleman syndrome (de novo maternal deletion chromosome 15)
williams syndrom (de novo chromosome 7)
Duplications:
portion of chromosome is duplicated resulting in extra genetic material
Translocations:
portion of one chromosome is transferred to another chromosome
Inversions:
a portion of the chromosome has broken off and turned upside down and reattached, causing the genetic material to be inverted
GDD
global developmental delay
delay in achieving 2 or more developmental milestones
motor speech cognition social emotional
Intellectual Disability
what is MR
mental retardation
IQ of 70-75 or less
Mild MR
50-70
Moderate MR
40-50
Severe MR
20-40
Profound MR
below 20
Lead Poisoning
- what it causes
- what AAP says to check up
no obvious symptoms
can cause GDD
AAP says screenings well check ups:
9-12 months and then again at 24 months
Cognitive Impairments (6)
1) able to learn fewer number of things
2) need more repetitions for learning to occur
3) slower response time
4) difficulty generalizing skills from one environment to another
perform skill in PR but not in natural environment
5) greater difficulty maintaining skills that are practiced
6) have limited repertoire of responses
Autosomal Trisomy
nondisjunction error during gametogenesis: meiosis
associated with advanced maternal age
Trisomy 21: extra copy if chromosome 21: Downs Syndrome
Trisomy 18 (Edwards syndrome)
Sex Chromosome Aneuploidy
name 2
cause
CAUSE: non disjunction error
- Turner’s Syndrome (X_): 45X: one less X chromosome or partially missing
- Kleinfelter Syndrome (XXY): 47XXY: extra chromosome
Turner’s Syndrome
ONLY FEMALES AFFECTED
1) short stature
2) DYSMORPHIC FEATURES: mishaped ears, short webbed neck, puffy hands and feet
3) HTN
4) hypothyroid: tired, delayed growth/height, heavy dry skin, brittle nails
5) lack estrogen: osteoporosis
6) kidney abnormalities (one kidney so avoid collisions/contact sports)
7) delayed/absent sexual development
8) frequent middle ear infections–balance/vestibular, hearing affects development of speech
9) visual spacial difficulties, difficulty judging distance and depth perception difficulties (crossing street, stairs)
Kleinfelter Syndrome
MALES ONLY
learning disabilities
speech and language delays
poor coordination
online Prader-Willi syndrome
Prader-Willi syndrome is a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes mellitus (the most common form of diabetes).
People with Prader-Willi syndrome typically have mild to moderate intellectual impairment and learning disabilities. Behavioral problems are common, including temper outbursts, stubbornness, and compulsive behavior such as picking at the skin. Sleep abnormalities can also occur. Additional features of this condition include distinctive facial features such as a narrow forehead, almond-shaped eyes, and a triangular mouth; short stature; and small hands and feet. Some people with Prader-Willi syndrome have unusually fair skin and light-colored hair. Both affected males and affected females have underdeveloped genitals. Puberty is delayed or incomplete, and most affected individuals are unable to have children (infertile).
Structural Abnormalities
4 syndromes
cri cu chat (de novo chromosome 5)
prader willi syndrome (de novo paternal deletion chromosome 15)
anglemand syndrome (de novo maternal deletion chromosome 15)
williams syndrom (de novo chromosome 7)
Hypotonia
what diseases associated with it
genetic syndromes
neurological diseases
endocrine
metabolic diseases
down synrome
cerebral palsy
spinal muscle atrophy
**hypotonia of unknown origin
Characteristics of Hypotonia
1) decreased strength
2) delayed motor sill development
3) poor attention/motivation
4) decreased activity tolerance
5) hypermobile joints (increased flexibility)
6) lean on supports (rounded shoulders)
Failure To Thrive
weight consistently below 3rd-5th percentile for age
progressive loss of weight to below 3rd to 5th percentile
decrease in percentile rank for height and weight in a short period
Conditions associated with failure to thrive
1) AIDS
2) CF
3) Hypothyroid
4) Fetal Alcohol Syndrome
5) Neurologic Impairment
6) Gastrointestinal Disorder: GERD
7) Cardiovascular disease
8) Renal disease
9) *poor parenting
10) prematurity
Cri-Du-Chat
online
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 high-pitched 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.
Cri-Du-Chat
how it happens
what sx
cri cu chat (de novo chromosome 5)
cat like cry
1) LBW
2) Failure to Thrive (suck/swallow imbalance)
3) Dysmorphic features: large mouth, microcephally
4) strabismus
5) hyotonia
6) congenital heart defect
7) scoliosis
8) GDD
9) MR moderate to severe
10) self injurous behavior (bang head, self biting, pull hair out)
Prader Willi Syndrome
1) hypotonia
2) obesity– lack normal hunger and satiety cues, low metabolic rate
3) strabismus
4) dysmorphic: short, small hands and feet, narrow face
5) respiratory difficulties
6) sleep apnea, daytime sleepiness
7) poor suck/swallow = feeding difficulties/failure to thrive
8) MR: low to moderate, some still have normal intelligence
9) GDDL average motor milestone acquisition twice the typical age –walk at 2
10 ) poor fine and gross motor coordination
11) behavioral issues: stubborn, tantrums, strong need for routines, physical aggression
12) scoliosis
13) developmental dysplasia hips (DDH) birth hips normal over time a problem develops
Angelman Syndrome
angleman syndrome (de novo maternal deletion chromosome 15)
1) hypotonia
2) tremors, jerky movements
3) seizures
4) scoliosis
5) wide base ataxic gait
6) dysmorphic: microcephalic, large mouth
7) expressed language impaired more than receptive (use sign language)
8) GDD
9) intellectual disability
10) ADD/ADHD
11) **inapropriate happy affect with episodes of laughing–telltale sign. SHOWS INTEREST IN PEOPLE-often misdiagnosed as Autism or CP
Williams Syndrome
williams syndrom (de novo deletion chromosome 7)
1) CV disease: elastin arteriopathy causes aortic and pulmonary stenosis, HTN
2) Radio-ulnar synostosis
3) mild cognitive impairment to normal intelligence, ADHD
4) delayed speech / fine / gross motor delay
5) visual / spacial difficulties
Single Gene Disorders
4 types
autosomal dominant
autosomal recessive
x linked recessive inheritance
mitochondrial disorders
Autosomal Dominant Disorders
3 examples
single mutated or abnormal gene from one parent (dominates) overrides the matching normal gene from the other parent
inherited from affected parent
examples
1) Osteogensis Imperfecta
2) Congenital Myotonic Dystrophy
3) Neurofibromatosis (NF1)
Neurofibromatosis
NF1
gene encodes neurofibromin
neurofibromin tumor suppressor keeps cells from growing and dividing too rapidly or uncontrolled. mutations can not regulate cell growth and divisions
cafe au lait brown or tan pigmented flat spots on skin –appear at birth but may develop later, can be normal brithmark. More than 6 or larger than 15mm
tumor benign or malignant: occur in nerves, develop in adolescence or adulthood
optic glioma age 0-4: vision loss (squinting, involuntary eye movements, decrease visual acuity)
scoliosis/kyphosis
pectus excavatum
learning disabilities: ADHD
poor coordination/clumsy
hypotonia
tibial dysplasia: causes bowing, could reasult in LLD
NF1 is associated with skeletal abnormalities such as short stature, scoliosis, and long bone fx with nonunion
decreased BMD, decreased bone strength, and low muscle mass all which may predispose them to fx and scoliosis (dont do contact sports)
online
What is the normal function of the NF1 gene?
The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many types of cells, including nerve cells and specialized cells called oligodendrocytes and Schwann cells that surround nerves. These specialized cells form myelin sheaths, which are the fatty coverings that insulate and protect certain nerve cells.
Neurofibromin acts as a tumor suppressor protein. Tumor suppressors normally prevent cells from growing and dividing too rapidly or in an uncontrolled way. This protein appears to prevent cell overgrowth by turning off another protein (called ras) that stimulates cell growth and division.
Biomechanical Disorders
metabolism errors caused by mechanical enzyme deficiencies
enzyme absent or not functioning properly. can cause neuromotor and or musculoskeletal deficits
- PKU
- Lysosomal Storage disease
Phenylketonuria
phenylalanine breakdown
part of newborn screening panel
panel looks for elevated level of metabolites
Lysosomal storage disease
lysosomal malfunction because of a deficiency of a single enzyme required for lipid or mucopolysaccharide metabolism
this results in acculmolation of undegraded materials within the lysosome
ie tay sach’s, goucher’s
Autosomal Recessive Disorders
same recessive mutated gene is inherited
typically neither parent is affected, no family hx
ie CF, sickle cell disease, spinal muscle atrophy, and biochemical disorders
Sex Linked Disorders
x linked recessive
x linked dominant
X linked Recessive
only males affected
females are carriers
classic family history–affected males and typical females
mom has abnormal gene on her X: 50% chance of passing it
female who inherits an c with a gene for a sex linked disorder usually no sx because has a normal copy x too
males who inherit an x chromosome with a gene for a sex linked disease have no second x to fall back on and therefore have the disease
examples:
Hemophelia
Duchenne Muscular Dystrophy (DMD)
Fragile X Syndrome
FMR1 gene on the long arm (q) of X chromosome responsible for making a protein needed for brain development– a mutation occurs and proper brain function is disrupted
a small section of the gene code (CGG) repeats itself on a fragile area of the X chromosome
1) hypotonia
2) hyperextensible joints
3) poor coordination
4) impaired balance
5) poor motor planning
6) GDD, walk by age 2, speech and language and motor delays
7) intellectual disability
8) autism spectrum disorder
9) seizures
Retts
cause
diagnosis
occurs almost exclusively in females
mutation X chromosome: MECP2 Gene
- MECP2 regulates other proteins needed in brain maturation
- development normal until MECP2 is needed
Diagnose
- -blood test for mutation
- -diagnostic criteria
Retts
vs autism
retts often misdiagnosed for autism
have autistic like features at an early age that disappear
in retts prefer people to objects and like affection
Retts
diagnostic criteria
essential diagnostic criteria
1) Normal development until 6-18 months (then regression)
2) normal head circumference at birth then SLOWING rate of head growth at 2-4 months old
3) MR
4) Gait abnormalities
5) STEREOTYPIC HAND MOVEMENTS
loses communication skills and purposeful use of hands and decelerationr of head growth
Retts
Stage 1
stage is for a few months to a year
At around 6-18 months: subtle slowing of development
- delays in grow motor
- less eye contact
Retts
Stage 2
between age 1-4 years: rapid or gradual loss of acquired skills
1) autistic-like behaviors: lose spoken language and social interaction
2) lose purposeful hand movements: self feeding: instead stereotypic hand movements: wringing, clapping, washing
3) gait abnormalities: unsteady wide based gait, toe walking, ataxia
4) slowed head growth causes microcephaly
5) behavior disturbances
6) tremors
Retts
Stage 4
reduced mobility
muscle weakness
rigidity spasticity dystonia
neuromuscular scoliosis 75% age 13–physical exam, educate parents
cognition, communication and hand skills do not usually decline
osteoporosis risk high risk for femoral fx
life expectency about 40 yrs
Retts
Stage 3
2-10 years
(many stay in this stage for most of their lives)
1) apraxia
2) seizures
3) communication skills may improve
4) motor difficulties
5) intellectual disability (moderate to severe)
6) breath holding, hyperventilation breath holding
Mitochondrial Disorders
alterations of mitochondrial DNA inherited from MOM
mtDNA codes polypeptides involved with oxidative phosphorylation
can only be transmitted by mom – zygote gets all its mitochondria from the egg
affect CNS and MUSCLE–have large amounts of mitochondria
CLINICAL FEATURES
1) myopathies generalized weakness, decreased balance
2) exercise intolerance
3) encephalopathy
4) retinal degeneration
Multifactorial Disorders
combination of genetic and environmental factors
the interaction of genetics and environment can result in birth defects
ie cleft palate
and adult onset disorders
ie cancer
common characteristics of genetic syndromes
hypotonia
failure to thrive
strabismus
GDD: delayed in developmental milestones: all, motor, learning…
microcephalic
Retts 4 stages
- start with normal development until 6-18 months
2 Rapid destructive: . 6-18 months: slow, regress, lose skills, head becomes microcephalic
- preschool to school age: apraxia, seizures, communication skills may improve, motor difficulties, intellectual disability (moderate to severe), breath holding, hyperventilation breath holding , motor deterioration
- motor deterioration
