Chromosomal disorders Flashcards
What is malformation?
Congenital anomaly which results in :
- Poor tissue formation
e.g. heart , neural tube
defects and cleft lip.
congenital anomalies - occur during embryogenesis (embryo development - up to 8 weeks after fertilisation)
What is deformation?
A secondary effect of unusual force on normal tissue (mechanical).
- most commonly due to a lack of amniotic fluid (oligohydramnios- low level of amniotic fluid) causing uterine compression.
Amnotic fluid -
- cushions baby from
injury
- prevents compression
of umbilical cord
(compression -----> reduced blood flow---->
Less O2 and nutrients to
baby)
- provides room to grow - anti-microbial.
What is disruption?
breakdown or disruption of normal tissue for instance
ex - amniotic bands
- Amnion (inner lining of amniotic sack ) damaged during pregnancy —–> amniotic bands (strands of fibrous tissue) float in amniotic fluid or stay attached to amniotic sac ) —–> amniotic bands wrap around foetus and disrupt normal development (constrict blood flow) ——-. limb deformities , can cause amputation.
Treatment
- Fetal surgery release the band to stop constriction - using Fetoscopy (introduction of an endoscope through the cervix or through the maternal abdomen and the uterine wall) - allows for visualisation of embryo.
-After brith - plastic and reconstructive
surgery
- Prosthetics - if amputated.
What is Dysplasia ?
The abnormal organisation or differentiation of tissues (deregulation).
Causes of congenital abnormalities?
- unknown causes - majority
- Chromosomal abnormalities
- Genetic mutations
- Multifactorial inheritance - (caused by both genetic + environmental causes)
- Environmental agents - tetra genic (alcohol , drugs (thalidomide , infections (rubella)
What can cause chromosomal disorders?
- change in chromosome number
(aneuploidy - gain or loss of 1 chromosome ) - diploid dumber no longer divisible by 23 as they would be either 45 or 47 chromosomes instead of 46 - change in chromosome structure
these changes result in loss or gain of genetic information effecting genes on the chromosome . - not all are problematic.
- however, pleiotropy - single gene effects multiple systems (a change to this gene can cause widespread problems)
What is Marfan Syndrome ?
genetic disorder effecting connective tissue.
- Mutation of fibrillin - 1 gene (FBN1)
- Fibrillin- 1 component of microfibrils part of scaffolding that holds cells together. Without it connective tissue lacks strength and structural intergrity - beocmes weak.- increase in transforming growth factor-beta (TGF- B) - effects connective tissue
Autosomal dominant - one parent needs to be a carrier - 50% chance of children getting it.
- Affect 1 out 5, 000 pl
Signs of Marfan syndrome?
(cardiovascular) , skeletal, and eye (ocular) systems are most often affected.
- mitral valve prolapse common - leads to other things , chest pain , congestive heart failure etc.
- Long arms and legs, fingers and toes ( arachnodactyly - abnormally long fingers and toes vs palm) (caused by overgrowth of long bones) - Tall - Thin body , little subcutaneous fat - curved spine (scoliosis ) - Flat feet - Hypertonia (lack tone ) - joint hypermobility - flexible , loose -abnormally deep acetabulum .
Facial features
- long, narrow skull (dolichocephaly),
- deep-set eyes (enophthalmos)
- an abnormally small jaw (micrognathia)
that may be recessed farther back than
normal (retrognathia)
variable expressivity - can vary btw pl even btw family members who have the condition.
Causes of a change in chromosome number ?
- Age - Significant risk factor
Incidence of Down syndrome is 1/1500 before the age of 20 and about 1/25 after 45 years
- Oocytes enter meiosis 1 , arrested at crossing over stage at 5 months gestation + 1st polar body (this not completed till ovulation)
- oocytes enter meiosis 2 , not completed until fertilisation)+ 2nd polar body
3 fertilisation - zygote
Oocytes paused in meiosis I for many years accumulate changes which predispose to non-disjunction.
- Lose of / damage to scaffolding and spindle proteins. Cohesin, is one protein which has been implicated.
-Non - disjunction - (Failure of either homologous chromosomes (meiosis I) or sister chromatids (meiosis II) to correctly separate)
What is Edward Syndrome ?
Trisomy 18
inherited extra chromosome 18 or part of chromosome 18. (3 copies of them)
- 2nd most common trisomy.
Poor prognosis - most die within a few week of life
- incidence - 1 in 3000 births
- more common in female babies.
Symptoms of Edwards syndrome ?
congenital heart defects (multiple)
ex - septal defect
- Patent ductus
arteriosus
- clenched hands , overlapping fingers
GI -
- Oesophageal Atresia - oesophagus ends in blind ended tube - discontinuation.
(can causes polyhydramnios - too much amniotic fluid in sac. as baby cannot swallow amniotic fluid - helps systems such as GI tract to develop. )
- Omphalocele bowel herniates into umbilical cord.
Kidney
- Kidney malformations - horse shoe kidney (2 kidneys joined at base)
what are the most common clinical signs of Edwards syndrome ?
- Clenched hand
- Overlapping fingers
- cleft lip
- Microcephaly (small head)
- Micrognathia (small jaw)
- L ow set ears
- prominent occiput
Treatment of Edwards syndrome?
No cure
Treat symptoms
e.g physiotherapy
heart issue treatment
- feeding tubes
infection - antibiotics etc
What is Patau Syndrome ?
Extra copy of chromsome 13 - trisomy 13
incidence - 1 in 5000
Symptoms / consequences of Patau syndrome ?
- Microcephaly
- Holoprosencephaly - failure of prosencephalon (forebrain) to divide into two - cause cyclopia - single eye as no division no formation of two eye cavities.
- Meningomyelocele - severe form of spina bifida.
severe intellectual ability.
omphalocele
septal defects - heart
cleft lip
- microphthalmia - small eyes
- polydactyly - many fingers
- cutis aplasia - failure of skin to develop - can manifest as skin lesion
