goal: expose pts to methods of prevention, avoidance, and/or ameliorations of these disorders
support them in making choices
knowing the odds and other more social aspects
what is the chance that I/we might have another affected child? (recurrent risk)
(most people don't think about affected child until it has already happened)
answer: 25% if disorder is autosomal recessive, 50% if autosomal dominant, if mutation v low odds
if rare sex-lined recessive answer 25% overall, 0% for sister, 50% for brother
trisomies: answer is slight incr over pop at same age
multifactorial: usu less than 10% but oft req use of empirical risk figures
conventional list of questions p124
1) what is exact dx?
2) what are known facts and results of examination of family hx/pedigree?
3) what is proband/consultands relationship to the patient?
4) Has mode of inheritance been established?
5) Empirical risk figures available?
6) Severity of anomaly?
7) Further exams of proband or relatives indicated?
8) Am I capable with my knowlege of dealing responsibly with the matter by myself? (may need to refer, most major metro areas have genetic svcs)
ultimate info, incr availability
raising questions about dz that can't be txd or cured
genetic info more complicated than it appears at first
find dz in fetus, embryo, find carrier, find dz in person before onset, confirm dz in presenting
lots of info on internet, careful
lots of support groups for specif dz
Family GENES (a mnemonic)
F = Fhx, sibs or mult generation occurrences in pedigree
G = groups of congenital abn, like in multifactorial
E = extreme/exceptional presentation of common condition, early onset, unusual rxn to infx of metab challenge
N = neurodevelpmental delay or degen, regression or deterioration
E = extreme/exceptional pathology, rare tumors etc
S = surprising lab values in otherwise healthy person
DNA tests available for:
amyotrophic lateral sclerosis
central core dz
Duchenne type MD, Becker-type MD
dystonia, myotonic dystrophy
Factor V-Leiden thrmbophilia
fragile X synd
breast and ov ca
hereditary nonpolyposis colon ca
hemophilia A & B
neurofibromatosis type 1
sickle cell dz
spinocerebellar ataxia type 1
spinal muscular atrophy
Tay-Sachs dz (autosomal recessive)
usu done at 15 weeks, mom may feel kick
US guided, risk of infx
fetal loss rate 1/300-400 pregs lost dt this procedure
not medically indicated unless risk of dz exceeds risk of fetal loss dt procedure
karyotype fetal cells and check fetal chemistry
cells are cultured-->week 17-18 you find out trimsomy 21
90% of mothers terminate when they know their child is Down's, this is a late abortion
alpha fetoprot in maternal serum
can ID down's, spina bifida, etc but with huge numbers of false pos and neg
if AFP comes in really low then amnio is recommended
if AFP comes in normal then woman can dodge amnio
causes more left handed babies??!
not done dt mutagenic risk
PRE-IMPLANTATION GENETIC DIAGNOSIS
PGD, emerging technology providing genetic info from early embryo
leading indicator for this is advanced maternal age
take one cell out and evaluate it, brings up abortion question again
done a lot in US, fairly expensive
mb someday able to ID abn gametes
QUESTION: burning fertility clinic, everybody's out except for one crying baby and a tank with 1000 viable embryos: which one do you save??
REASONS FOR PRENATAL DX AND GENETIC COUNSELING
advanced maternal age
prior child with xsm defect
prior hx of miscarriage esp many repeats
known xsm defect in 1+ parents (transloc downs carrier?)
familial hx of gene dz in fam
part of specific ethnic high risk group
may be able to repair DNA
or block fx of defective genes
DNA scans for each patient, risks identified for several dzs
ISSUES AND ETHICS
docs are not well enough trained
rapid changes in the field
"human quality control"???
what is "normal"???
if we remove diversity the longterm population effects could be devastating
(stop evolution? reduction in diversity has been bad for other sp)
will we be changing the "construction documents"???
genetic testing: privacy, reliability, insurance, untreatable
gamete banking: artificial insemination implications? sperm from nobel laureates available.
cloning: sheep, monkeys etc successfully cloned, human cloning is already possible