genetic diseases Flashcards
Primary ovarian insufficiency - POI - Depletion or dysfunction of
ovarian follicles with cessation
of menses before age 40.
Affects ~1% of women
under 40 years old. &
~0.1% under 30 yrs
Basic Inheritance
Genetic mutations:
Dominant: one copy of
mutation can pass this disease
on to future generations.
Recessive: Disease only occurs
when two copies of the gene
are inherited (one from each
genetic contributor).
X-Linked: Mutation found on
the X-Chromosome. Disease
usually occurs in males since
they only have one Xchromosome.
Primary ovarian insufficiency - POI - is it regular?
Ovarian function is
intermittent or unpredictable. 5-10% could have
spontaneous
conception/deliver
Primary ovarian insufficiency - POI - what hormones do we test for? and what is the timeline?
FSH/ E2 are measured on at least two separate
occasions (with more than 4 weeks of
interval), elevated FSH levels (greater than 25 IU/L)
POI - what type of genetic abnormalities?
(PO has C12)
Chromosomal
abnormalities, Genetic
polymorphisms, and Single
gene mutations
POI can be Non-Genetic
(Po ME AI)
Autoimmune, Iatrogenic (relating to illness),
Metabolic, Infectious or
Environmental
genetic screening policy - Spring will offer comprehensive, expanded panel genetic carrier screening to
all patients.
Horizon 421- natera
A decision regarding completing–Horizon 421 is required for genetic
contributors pursuing ovulation induction, IVF and/or frozen embryo
transfers (if not completed prior to embryo cryopreservation). Genetic
carrier screening is encouraged but not required for patients pursuing
oocyte cryopreservation.
Patients with prior ECS screening, see Acceptable panels
chart (CN11). Those who completed acceptable panel do
not need to sign a waiver and are NOT encouraged to
complete Natera 421
If panel not listed, we will recommend H421 or
waiver.
Expanded panel carrier screening cannot be waived by gamete donors
managed by Spring. This includes identified sperm donors, identified
and non-indentified ovum donor’s and spring’s egg bank, Nest, ovum donors
CN 11 policy—ECS testing
Treatment should not be started until one of the scenarios is met:
Testing has been waived/declined
“Extended genetic carrier screening waiver” signed both genetic contributors
Testing Complete: Negative Result (s)
Oocyte contributor alone or both gamete contributors
Testing Complete: Positive Result(s)
Discordant (both tested NOT carriers of same conditions)
Oocyte contributor tested, positive is NOT on “No Go” List & Partner NOT testing
15 min. call w/GC required ($100) & Sign waiver
Both positive for same mutation & complete proper follow up
See CN 11 for all variations of positive results and proper follow up
X link is only tested in the
provider
carrier screening results pending - One or both results pending and proceeding with Tx.
Alert must be added to chart: “PENDING HORIZON”
* They must sign an appropriate waiver.
* Not applicable if results from one genetic contributor are positive
for a condition on Spring’s “No Go” list then they must wait for
pending results of the other genetic contributor.
Pending Genetic Carrier Screening waiver:
- IUI
- IVF
- NOTE: NYC- Patients are NOT allowed to proceed with treatment
with pending results, this waiver is not applicable at that site.
The “NO GO” Genetic Diseases
(no go CT FGS) (cat no go fgs)
Cystic Fibrosis
Tay-Sachs
Fragile X Syndrome
Gaucher
Spinal Muscular Atrophy
Cystic Fibrosis
Cystic fibrosis is a progressive disease
that affects the lungs, pancreas and
other organs. - won’t be tested on this
In people with
CF, mutations in the cystic
fibrosis transmembrane
conductance regulator
(CFTR) gene cause the CFTR
protein to become
dysfunctional.13
*No cure, treatment can ease
symptoms, reduce complications
and improve quality of life
*Congenital bilateral absence of the
vas deferens (CBAVD) is found in 1%
to 2% of males with infertility and is
present in 6% of
obstructive azoospermia cases.
*Nearly 95% of men with cystic fibrosis have CVAD
Tay-Sachs
(Tay is fat)
Caused by an absence of an enzyme(betahexosaminidase A) that helps break down fatty
substances (GM2 gangliosides) in the body.
Toxic levels of gangliosides in the brain and
spinal cord affect the function of nerve cells.
Three forms of Tay-Sachs
Infantile (most common)-survival only
a few yrs
Juvenile (range of severity)-survival
into teen yrs.
Late onset/adult (least severe/less
common)
No cure, only treatments to relieve
symptoms and increase quality of life
Ashkenazi Jewish descent are commonly at
risk
POI usually have low levels of
estrogen - so bone problems, etc.
concordancy
(concordant diseases)
both providers positive for the same disease - absolutely need genetic counseling if this is the case
PGTA
(A line up)
autosomal - just lining up
PGTM - when to do it?
when one is a carrier
Fragile X Syndrome
(fragile autism)
Affects 1 in every 4,000 males and 1 in every 6-8,000 females
Leading known genetic cause of autism
More often the egg provider that has fragile X
Causes a range of developmental problems, learning disabilities, and
cognitive impairment
Physical features:
long and narrow face
large ears
a prominent jaw and forehead
unusual flexible fingers
flat feet in males
Fragile X Syndrome,
cont. (continued)
(fragile X is the former 1 brain)
Defect in the FMR1 Gene on
the X- Chromosome.
This protein is required for the
brain to develop normally.
(synapses->nerve cells)
Fragile-X mutation-> FMR1
gene is switched OFF due to
excessive CGG repeats
premutation - 55-199 # of CGG repeats - some symptoms reported - always need genetic counseling if this is the case
Gaucher Disease
(gaucho has a big belly)
Individuals are missing an enzyme that would break down lipids
Main Symptoms:
Swollen belly - enlargement of spleen and liver
Bone pain and easily fractured bones
Anemia, low blood counts and fatigue
Bleeding and bruising problems
Types:
1: most common, treatable, and normal brain development
2: rare, severe neurological abnormalities, fatal within the first 2
years
3: slower onset than type 2 and some survive until adulthood
Spinal Muscular Atrophy
Degeneration of motor neurons
Damages and kills specialized nerve cells in the brain and spinal cord
Leads to progressive muscle weakness and atrophy
Depending on the type, severity can lead to death
most common is type I (Werdnig-Hoffman disease)
Type 1 usually evident at 6 months of age
No cure
Treatment helps to lessen symptoms
Other symptoms:
Muscle atrophy
Arthritis
Trouble breathing
Trouble eating or swallowing
