ATAXIA-GENETICS AND FAMILY PLANNING

Matthew Bower, MSUniversity of Minnesota Ataxia Center

DISCLAIMER The information provided by speakers in any presentation

made as part of the 2012 NAF Annual Membership Meeting is for informational use only.

NAF encourages all attendees to consult with their primary care provider, neurologist, or other health care provider about any advice, exercise, therapies, medication, treatment, nutritional supplement, or regimen that may have been mentioned as part of any presentation.

Products or services mentioned during these presentations does not imply endorsement by NAF.

PRESENTER DISCLOSURES Matt Bower, MS, CGC The following personal financial

relationships with commercial interests relevant to this presentation existed during the past 12 months:

No relationships to disclose or list

TAKE-HOME POINTS: Ataxia genetics are too complicated for

a 30 minute talk! I will be speaking in broad generalizations Consult with your physician or genetic

counselor about your specific questions

TAKE HOME POINTS Plan ahead

Many testing options require advance knowledge of your genetic status

TAKE HOME POINTS Family planning decisions are personal

decisions- there is no “right” answer.

GENETICS REVIEW- DOMINANT INHERITANCE

SCA1-36 (and counting!)

These men are both affected with ataxia

GENETICS REVIEW- DOMINANT INHERITANCE

SCA1-36 (and counting!)

Each of these siblings has an independent 50% risk

GENETICS REVIEW- RECESSIVE INHERITANCE Friedreich, AOA1, AOA2, AT, and

others

These two sibilngs have ataxia

GENETICS REVIEW- RECESSIVE INHERITANCE

Both parents are carriers

GENETICS REVIEW- RECESSIVE INHERITANCE

These two siblings have a 2/3 (67%) carrier risk

GENETICS REVIEW- RECESSIVE INHERITANCE

Carrier risk for spouses depends on how common the ataxia is in the general population

STEP 1- WHAT KIND OF ATAXIA IS IN MY FAMILY?

Diagnostic testing- Testing someone with symptoms to figure out the type of ataxia in your family. This person may be you (if you have

symptoms), or it may be another family member.

Genetic testing is only accurate if the type of ataxia in the family is known.

Important to obtain actual test results, if possible.

STEP 2- WHAT IS MY GENETIC STATUS? In order to determine if your children

may be at risk, it may be important to determine your own genetic status Dominant ataxias

If you have symptoms, you could have diagnostic testing.

If you are asymptomatic, you could have predictive testing.

STEP 2- WHAT IS MY GENETIC STATUS? In order to determine if your children

may be at risk, it may be important to determine your own genetic status Recessive ataxias

Affected with the familial ataxia-diagnostic testing

Biological relatives of affected individuals (carrier testing)

Non-biological relatives of affected individuals (i.e. people who marry into the family) carrier testing

STEP 3- WHAT ARE RISKS TO FUTURE CHILDREN?

Dominant ataxias If you have the ataxia gene, your child will have

a 50% risk (regardless of whether it is a boy or girl)

If you did not inherit the ataxia gene, then your children are not at risk (i.e. does not skip generations).

Recessive ataxias If both parents are carriers, the risk to each

child is 25% (regardless of whether it is a boy or girl)

STEP 4- WHAT ARE MY OPTIONS? Having children without any genetic

testing Adoption / Foster parenting Pregnancy with prenatal diagnosis In vitro pregnancy with donor egg donor sperm In vitro pregnancy with genetic testing

(pre-implantation genetic diagnosis)

PRENATAL DIAGNOSIS Definition- Genetic testing done during

a pregnancy to determine if a fetus is affected with the familial ataxia

Two procedures are available: Chorionic villus sampling (CVS) Amniocentesis

AMNIOCENTESIS• Amniotic fluid is removed using a thin needle.• Cells from amniotic fluid can be tested for the

familial ataxia• Generally done after 15 weeks gestation• Small risk of miscarriage (< 0.5%)

CVS• Generally done 10-13

weeks gestation• Not as widely

available as amniocentesis

• Risk of miscarriage varies from center to center- generally <1%

INTRAUTERINE INSEMINATION WITH DONOR SPERM

If the father is affected with a dominant ataxia, or a carrier of a recessive ataxia, patients can utilize a donor sperm sample Known unaffected relative Anonymous donor

Does not require IVF procedures

IN-VITRO FERTILIZATION Sperm and egg are mixed in a petri

dish to create embryos.

IN-VITRO FERTILIZATION WITH DONOR EGG IVF (all by itself) does not alter the risk

for ataxia in children. If the mother is either affected with the

ataxia, or is a carrier, couples can do in-vitro fertilization using an egg from a healthy donor.

PRE-IMPLANTATION GENETIC DIAGNOSIS Embryos created through IVF One cell from each embryo is tested to

determine if the embryo is “affected” with the familial ataxia.

Only “unaffected” embryos are transferred to the uterus.

PRE-IMPLANTATION GENETIC DIAGNOSIS (PGD)

PRE-IMPLANTATION GENETIC DIAGNOSIS (PGD)

Braude, P., et al., Preimplantation genetic diagnosis, Nature Reviews Genetics 3, 941–955

NON-INVASIVE PRENATAL DIAGNOSIS Fetal DNA is known to be in mother’s

blood during pregnancy Tests have recently been developed to

diagnose some specific fetal conditions from a maternal blood draw No risk of miscarriage Not yet available for conditions like ataxia.

SUMMARY- WHAT ARE MY OPTIONS? Having children without any genetic

testing Adoption / Foster parenting Pregnancy with prenatal diagnosis In vitro pregnancy with donor egg donor sperm In vitro pregnancy with genetic testing

(pre-implantation genetic diagnosis)

STEP 5- WHAT IS RIGHT FOR ME? Does my future child’s ataxia status have

any bearing on my decision to have children? Importance of being the biological

mother/father Financial- will insurance cover the costs of

procedures? Are there medical risks with some of these

technologies Emotional investment with in-vitro

fertilization technologies.

THANK YOU

MY DEFINITION OF FAMILY PLANNING