Exam 2 Flashcards
Physical features of fragile X in females
More subtle, menstrual cycle problems in early menopause and ovarian cysts but generally more of a cognitive problem
Missense mutation
Replacement of a single amino acid for another in the protein chain example: PKU
2nd most common genetic cause of ID
Fragile X syndrome
Nonsense mutation
Replacement of a single amino acid causes premature termination of protein formation example: Neurofibromatosis
Triplet Repeat Expansion
Repeated multiple times of a certain regions of genes, marked expansion can cause a gene to be turned off, occurs in fragile X
Most common form of ID in males
Fragile X syndrome
Who should be screened for fragile X
individuals of either sex with ID, DD, or asd especially if there is physical or behavioral features, family history of fragile X, relatives with undiagnosed ID
Individuals seeking reproductive counseling who have a family history of fragile X or family history of undiagnosed ID
Fetuses of known carrier females
Physical Characteristics of Fragile X syndrome in males
Long narrow face, large ears, prominent jaw and forehead, larger head circumference than other ID people, arched palate
Progression of cognitive performance of females with fragile X
Only small % of females show IQ decline (unclear why)
Percent of children receiving SPED services with Fragile X
1.1%
Triple Repeat Expansion becomes ___ severe from one generation to the next
more
Cognitive impairment in fragile X
Wide range in IDD, early milestone delays
One third of all x linked causes of ID
Fragile X syndrome
Phenklketonuria (PKY) cause, symptoms, prevalence, how to detect
Cause: Single base substitution causes error in production at 12q14.1
Symptoms: Accumulation of phenylalanine in blood that cause brain damage
Prevalence: 1 in 10,000
How to detect: newborn screening can detect PKU
Reasons for progression of cognitive performance of males with fragile X
Reasons are unclear, theories: due to age related changes in size of brain structures important for learning, attention and memory (STG, hippocampus), lack of FMR1 protein causes damaging effects that extend beyond childhood
If mother passes fragile X to offspring
Almost always TRE
Generally, males with full mutation of fragile X show ____ characteristics
clinical
Progression of cognitive performance of males with fragile X
IQ declines over time because of slower rate of acquisition of skills
1-5 yrs: 55 (mean iq)
6-10 yrs: 50
11-15 yrs: 43
16-20 yrs: 39
How was fragile X diagnosed before FMR1 gene was identified
visual inspection of fragile X symptoms – accurate for affected males and females with ID but couldn’t detected unaffected females, males for prenatal diagnosis
More than ___ of females with full mutation have symptoms, the other protected from symptoms by the normal ____ gene on their ____ chromosome
50%, FMR1, 2nd
If father passes on fragile X to daughter
Usually no TRE but daughter has premutation
Processing type and language for males with fragile X
Simultaneous processing > sequential learning, echolalia, preservative speech, word finding difficulty
Point mutation / single base pair substitution
Most common type of mutation, usually not a problem but two types - missense mutation and nonsense mutation
What does untreated PKU lead to
ID, Microephaly (Small head), Abnormal walk, Seizures
Number of CGG repeats and their classifications
6 - 45: normal, 45 - 54: grey zone, 50 - 200: unstable mutation (premutation carriers), 200 - 3000: affected with full mutation
Why is it called fragile X syndrome
Because the bottom tip of the long arm of the X chromosome constricts and becomes threadlike: fragile
Gene fragile X screws up
FMR1
Rett syndrome: mutation locus, prevalence, characteristics
Locus: Xq28
Only in females - fatal for males, 1 in 10,000
normal development until 6 - 9 months, post natal microcepahly and ID, progressive deterioration, features of autism, characteristic hand-wringing
Fragile X genetic disorder type
Recessive X linked disorder, Single gene disorder
What is triple repeat expression in fragile X
describes the repetition of CGG gene on the X chromosome
Fragile X syndrome prevalence rates in males and females
Males: 1 in 4000, Females: 1 in 4000 - 6000
Insertions and Deletions
One or more base pairs can be inserted or deleted in the chain, can lead to a frame shift which causes production of nonfunctional protein
Number of women in the US that are Fragile X syndrome premutation carriers
1 million
3 types of genetically distinct males of fragile X in males
Fully methylated CGG repeats: mild to moderate IQ,
Mosaic for Fragile X: borderline to low average IQ,
Unusual pattern males: average to low average IQ
Most common inherited cause of ID and ASD
Fragile X syndrome
Indicator for testing fragile X syndrome
History of excessive shyness in mother
Comorbid behaviors with Fragile X
Autism (10 - 30%) fewer for females (15%)
2 - 5% of asd people have fragile X
90% of males have 1+ ASD symptom, of note is gaze avoidance is usually less impaired than autism, and the fragile X handshake (shake hand but no eye contact until they look away)
Comorbid behaviors with Fragile X for females
Full mutation: less severse than males but problems relating to others, (shy, social withdraw, avoidance, isolation etc)
Premutation: may be socially sensitive or anxious than full mutation peeps
Expression of fragile X gene mutation is influenced by what
which parent passes it on
What does cognitive impairment in females for fragile X rely on
Proportion of cells with normal X chromosome activation to Fragile X cells. Therefore, females with full mutation generally less impaired than males because they produce more normal FMR1 protein from their normal chomsome
Only a ___ number of mutations are viable
small
Likelihood of a mutation increases…
with the size of the gene
Prevalence of Tay-Sachs
1 in 112,000, prevalence in Ashenazi Jews 1 in 3800
Technical physical characteristics of fragile X syndrome in males
double jointedness and flat feet (if loose CT), ear infections because of poor tube drainage, and mitral valve prolapse (improper closure of value between heart’s upper and lower left chambers)
As well as macroorchidism (large testicles) which is present in 80 - 96% of postpubertal males and can also found in other adults with ID but its bigger in FRX
Tay-Sachs disease
Mutation in gene 15q23-24, deficency in enzyme Hex-A, Progressive neurological deterioration: deafness, blindness, seizures, fatality by 5yrs old
Autosomal Recessive Disorders
Abnormal gene inherited from both mom and dad example: Tay-Sachs disease, casued by a single abnormal allele
Neurofibromatosis
Nonsense mutation, unaffected children don’t carry, 50% of cases arise from new mutations
How is the fragile X gene screwed up
Contains repeated CGG DNA sequence, does not produce the normal protein that helps postnatal brain development
Cognitive impairment of fragile X in females
Depends on amount of FMR1 protein produced, Verbal skills better than performance abilities, not reliant on the number of repeats
Neurofibromatosis cause
Lack of neurofibromin causes multiple neurofibroma tumors on body and brain
Mutations
Alteration in the DNA that typically occurs during mitosis and meiosis, usually, the new cell dies or is repaired
Neurobiological symptom of repeated CGGs
Turns off gene to methylate causing decrease in FMR protein
Characteristics of PWS that most often impact daily living
Hyperphagia, Compulsive behavior/preservations
Hyperphagia definition
Abnormally increased appetite for and consumption of food, thought to be associated with a lesion of injury in the hypothalamus
Hypothalamus role in the body
Hunger and thirst, sleep wake cycle, temperature regulation, Metabolism, reproductive function
When is the onset of PWS
2 - 4 years old
Severity of PWS
Varies person to person but always some hyperphagia
Behaviors of hyperphagia and pws
repeated questions about meal contents and meal time, Food seeking and hoarding, and eating unappealing substances
What is ghrelin
Hormone secreted by the stomach, hypothalamus, pituitary, and other sites
involved in energy balance and appetite regulation
blood concentration of ghrelin are lowest after meal consumption, then increase
PWS prevalence
1 in 15,000
PWS and muscle tone
Hypotonia at birth and poor muscle tone throughout life
PWS has ___ metabolic rate
slow
PWS kids have ___ stature and ____ extremities
short, small
Growth hormone treatment in PWS
Incrases height, decreases body fat, increases muscle mass, improves weight distribution, increases stamina, increases bone mineral density, mixed findings on behavior
Cognitive/Vehavioral problems in PWS
Low average to mild moderate ID
Emotional outbursts/tantrums
Compulsive behavior
Skin picking
Increased risk for ASD
in PWS ____ requirement for calories
Decreased, due to hypotonia, decreased activity, and short stature
Hypotonia
Decreased muscle tone
In PWS ____ threshold for vomiting and ____ pain perception
High, decreased; leads to eating a lot of food without discomfort
What can negatively impact prenatal development
Maternal Stress, Environmental Toxins: Toxoplasmosis, lead, plastics, mercucry, diet, maternal infections, drugs and alcohol
Nutrition as an influence on prentala development
Bad maternal nutrition can result in premature birth and low birth weight, lack of folic acid can increase risk of neural tube defects
Stress as an influence on prenatal development
low birth weight and premature births
What is a critical period
Period of time that organs develop
True or false: During a critical period, a certain organ is vulnerable to toxin, viruses, and genetic abnormalities
True
How come If there is 40 weeks of pregnancy but 38 weeks is full term
38 refers to the date from the woman’s last period
True or False: In the first couple of weeks, (before implantation) you’re susceptible to teratogens
False
Mother’s Age as an influence onf prenatal development
More likley to have difficulty getting pregnant, miscarriages, stillbirths
50% of pregancnies among women in their 40 and 50s result in miscarriage
The TORCH Maternal Infections
Toxoplamosi, Others (HIV, syphilis), Rubella, Cytomegalovirus, Gential Herpes
Effects of TORCH
neurological disorders, deafness, blindness, mental disability, damage to bones, eyes, ears, or heart
The birthweight categories
Low birth weight
