GENO- Clinical consequences of chromosomal disorders Flashcards
give some examples of aneuploidy conditions
T21,18,13
45X, 47XXY, 47XYY
give an example of microdeletion or microduplication syndrome
missing / extra chromosomal material
22q11.2 deletion - Williams syndrome
copy number variation - number of repeat sequences varies between individuals, may be benign or disease causing
how can translocation produce genetic abnormalities
rearrangement of chromosomes
balanced/ unbalanced
may have other arrangements - inversion etc…
why is understanding abnormalities important
they causes: infertility miscarriage / still birth congential anomalies medical problems / disabilities can be carried in families without symptoms emotional burden of affected people and their relative reoccurrence risk financial burden to the NHS
describe the clinical features of T21
facial - epicanthic folds, flat nasal bridge, macroglossia
hands and feet are small - small palmar crease, sandal gap
other - short stature, hypotonia, developmental delay, cardiac malformations, hypothyroidism, dementia, 20-fold increase in leukaemia
how is T21 diagnosed
qf-PCR
other important investigations
karyotype of foetus - determine the origin
parental karyotypes - if translocation / rearrangement
describe the clinical presentation of Edwards syndrome
antenatally - raised nuchal, intrauterine growth restriction, multiple congenital abnormalities cardiac malformations renal malformations exomphalos - abdominal wall defect overlapping fingers - rocker bottom feet intellectual disability
describe the clinical presentation of Patau’s syndrome
antenatally- raised nuchal/ IUGR/ multiple congential anomalies holoprosencephaly cleft lip cardiac malformations polydactyly exomphalos renal malformations cutis aplasia intellectual disability
describe the clinical presentation of turners syndrome
antenatally - raised nuchal, foetal oedema, congential abnormalities broad, webbed neck low hairline cardiac malformation renal abnormalities short statue absent puberty infertility normal IQ
describe the clinical feature of Klinefelter syndrome
phenotypically male tall female fat distribution gynaecomastia hypergonadotropic hypogonadism with decreased testosterone small testes higher rate of autism and ADHD
what types of translocations are there
reciprocal
Robertsonian
what is meant by balanced / unbalanced translocations
unbalanced - missing / extra material
balanced - no net loss/ gain of material, no phenotype unless breakpoints disrupt a gee, risk of unbalanced offspring
describe the clinical features of mosaic trisomy 8
deep palmar / planta creases facial dysmorphism congential heart disease structural abnormalities learning difficulties
describe the clinical features of 22q11.2 deletion syndrome - diGeorge,
characteristic face, cardiac malformations, cleft palate, hypocalcaemia, immune deficiency, velopharyngeal insufficiency, developmental delay and intellectual disability
describe the clinical features of 7q11.2 deletion - williams syndrome
characteristic face, supravalvular aortic stenosis
mild / severe intellectual disability
hypercalcaemia
