complications of development Flashcards
3 types (and prevalence) of mal-development
genetic (30%), environmental (15%), multifactorial (55%)
examples of categories of mal-development
eye mosaic (different coloured eyes), cleft lip/palate, trisomy 18 (weeks to months survival), trisomy 13, polydactyly, chimerism, thalidomide
chain of development
change in numbers of conceptuses or foetuses that develop
examples of gross changes in numbers of conceptuses or foetuses that develop
twins, triplets (very early split of fertilised eggs from identical), chimaera (2 genetically distinct conceptuses which combine very early in development and form one individual with no reaction to different genetically distinct cells; example is Blaschko’s lines)
extreme between multiple pregnancies
conjoined twins caused by incomplete inner cell mass separation
what determines outcome of conjoined twins
extent of joining
what else can change development and gene expression
distribution and content of cells and chromosomes
3 patterns of cellular distribution
mosaicism (non-disjunction), distribution of cells between inner cell mass and trophectoderm (placenta), chimerism
what is mosaicism (non-disjunction)
differences between cells within one individual (if most cells are normal, then impact is modest)
describe distribution of cells between inner cell mass and trophectoderm
abnormal cells will move into placenta (easier process), normal cells will move to embryo (more difficult process), so genetics of infant and placenta are different
what is chimerism
fused multiple zygotes
example of mosaicism
heterochromia (different coloured eyed)
what is eye colour gene chromosome
15
when does eye differentiation begin and significance
day 22 post-fertilisation (so chromosomal problem must predate this to cause heterochromia)
3 types of chromosome problems and outcome
too many, too few (aneuploidy), translocations; all give rise to syndromes
common chromosomal syndromes caused by too many chromosomes (XY linked)
Kleinfelter’s syndrome (XXY) and other more severe forms, including XYY
what happens to X chromosome in females (XX)
one is inactivated in females
effect on severity of increasing number of X chromosomes in too many chromosome abnormalities
more severe
common chromosomal syndromes caused by too many chromosomes (autosomal)
Down’s syndrome (chromosome 21; heart problems determine survival), Edward’s syndrome (chromosome 18; live <2 weeks), Patau’s syndrome (chromosome 13; most die before birth)
exception trisomy chromsome which has never been detected in miscarriage or birth
chromsome 1, as it carries so many genes (largest chromosome) that defect prevents implantation and is lost immediately
symptoms of mosaic or partial extra chromosomal material compared to complete trisomies
less severe
common chromosomal syndrome caused by too few chromosomes (XY linked)
Turner’s syndrome (X0; female, short stature, infertile); Y0 is not viable
common chromosomal syndromes caused by too many chromosomes (autosomal)
no complete losses are viable, but partial chromosome loss syndromes are possible
what are translocations
altered distributions of chromosomes
example of XY linked translocation
XX male as XY translocation
what are autosomal translocations linked with
development of tumours e.g. lymphoma, leukaemia, sarcoma
what affects function of gene product
altered expression (e.g. more/less key regulator), or mutations in gene (key regulator, receptor etc.)
3 examples of gene defects
piebaldism (KIT), Holt-Oram syndrome affecting heart and hands (TBX5), achondroplasia (gain of function mutation in FGFR3 - switched on permanently)
what happens to heart and hand in Holt-Oram syndrome (variable in effects even on same person e.g. both hands affected differently)
overlarge heart as atrial septation defects, correct number of digits on hand but abnormalities (e.g. thumb)
what happens in achondroplasia
defects in conversion of cartilage to bone and lack of bone growth (especially large bones, such as humerus and femur)
organism size vs number of genes, and therefore what contributes to how our bodies work
don’t correlate, so microbiome has large effect
2 other terms which mean the same as birth defect
congenital malformation, congenital abnormality
define birth defect
change in pattern of development (teratology or dysmorphology)
define teratogen
any agent that can disturb the development of an embryo or fetus (usually most vulnerable in early stage, with some exceptions)
3 types of teratogen
infectious agents, physical agents, chemical agents
6 systems which can be affected by teratogens
limbs and digits, urogenital, heart, CNS, face, lungs
describe polydactyly and when it occurs
nothing stands out except additional digit; forelimb bud appears at day 27/28, and hindlimb bud at day 29: limb grows out from lateral plate mesoderm rapidly under control of special signalling regions and is fully formed by day 56, so abnormality between day 27 and day 56
what controls pattern of digits development
sonic hedgehog is polarising factor for limb development, mediating ZPA cells
facial development: where do eyes, ears and nose originate from before migrating to correct place (by week 10)
eyes on side of face, ears part way down legs, nose where eyes
what forms and are filled in during facial development, and what is the outcome if not filled in
clefts; cleft lip and palate (early surgery after birth and healing process much more rapid)
what is spina bifida
twinning of soft tissue in spine (variable protrusion of tissue (CSF or spinal tissue) from spine external to body) - anatomically corrected by surgery but nerve damage less easily repaired
what directs formation of spinal bone
nervous tissue, as where this doesn’t develop, bone overlying it doesn’t form
what causes spina bifida and when
poor sealing of neural tube (neuralation failure), forming gap which tissue leaves by (day 22/23), so problem present within 4 weeks of pregnancy
what can cause poor sealing of neural tube, causing spina bifida
folic acid deficiency
when should folic acid be given
ideally 3 months before pregnancy (during which egg matures before fertilisation), or more
what is anencephaly
defect in skull and brain development during day 22/23, with female babies affected more commonly than male
what can cause anencephaly
folic acid deficiency (similar to spina bifida)
when does limb development occur
days 24-56
what were the variable consequences of thalidomide (drug for morning sickness, so taken during first trimester)
limbs affected (upper limbs > lower limbs), as well as deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness
what is thalidomide used for now
some leprosy and cancer treatments (mess up blood vessel development)
effect of thalidomide on blood vessels in limbs
affects rapidly developing blood vessels, causing cell death in developing limb bud so couldn’t grow out properly
when does thalidomide affect limb development
days 25-28
what does respiratory distress syndrome cause, and when does this affect
malfunctioning lungs with no surfactant, affecting premature infant between 24-31 weeks
preventions of respiratory distress syndrome in premature infant
injection of glucocorticoid
