Chromosomal disorders

Question 1

What is malformation?

Answer 1

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)

Question 2

What is deformation?

Answer 2

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.

Question 3

What is disruption?

Answer 3

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.

Question 4

What is Dysplasia ?

Answer 4

The abnormal organisation or differentiation of tissues (deregulation).

Question 5

Causes of congenital abnormalities?

Answer 5

• unknown causes - majority
• Chromosomal abnormalities
• Genetic mutations
• Multifactorial inheritance - (caused by both genetic + environmental causes)
• Environmental agents - tetra genic (alcohol , drugs (thalidomide , infections (rubella)

Question 6

What can cause chromosomal disorders?

Answer 6

• 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)

Question 7

What is Marfan Syndrome ?

Answer 7

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

Question 8

Signs of Marfan syndrome?

Answer 8

(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.

Question 9

Causes of a change in chromosome number ?

Answer 9

• Age - Significant risk factor
  Incidence of Down syndrome is 1/1500 before the age of 20 and about 1/25 after 45 years

1. Oocytes enter meiosis 1 , arrested at crossing over stage at 5 months gestation + 1st polar body (this not completed till ovulation)
2. 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)

Question 10

What is Edward Syndrome ?

Answer 10

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.

Question 11

Symptoms of Edwards syndrome ?

Answer 11

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)

Question 12

what are the most common clinical signs of Edwards syndrome ?

Answer 12

• Clenched hand
• Overlapping fingers
• cleft lip
• Microcephaly (small head)
• Micrognathia (small jaw)
• L ow set ears
• prominent occiput

Question 13

Treatment of Edwards syndrome?

Answer 13

No cure

Treat symptoms
e.g physiotherapy
heart issue treatment

• feeding tubes

infection - antibiotics etc

Question 14

What is Patau Syndrome ?

Answer 14

Extra copy of chromsome 13 - trisomy 13

incidence - 1 in 5000

Question 15

Symptoms / consequences of Patau syndrome ?

Answer 15

• 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

Question 16

Types of Spina bifida ?

Answer 16

• Spina bifida occulta - Mild - incomplete fusion of vertebrae
• meningocele - meninges protrude btw opening located btw unfused vertebrae.

Myelomeningocele - most severe - severe disability -
0 spinal cord damage-
unfused
0 Meninges protrude posteriorly btw unfused vertebrae.

Question 17

Meaning of Aplasia

Answer 17

Failure of tissue / organ to develop.

Question 18

Diagnosis of chromsomal anomalies ?

Answer 18

prenatal ultrasound - look forr nuchal translucency - indicates hydramnios

1st trimester - lower HCG , PAPP-A serum levels

Question 19

What is Turner syndrome ?

Answer 19

X chromosome completely or partially absent.

1 in 3000 Females

• Effects Females
• karyotype - 45

Question 20

Signs of turner syndrome ?

Answer 20

• Webbed neck (extra folds on skin)
• infertility - ovarian hypofunction/ pre- mature ovarian failure - ovarian tissue degenerates before birth .
• Some - No puberty unless given hormone relacement.
• low hairline on back of neck
• Short stature
• widely spaced nipples
• Most have normal intelligence.

Question 21

What is Klinefelter syndrome ?

Answer 21

boys - 1 in 1000

• Have extra X chromosome so XXY.

Karyotype - 47

Question 22

What are the signs of Klinefelter Syndrome ?

Answer 22

• Lack of Testosterone - primary testicular insufficiency.
• Small testes
• Breast growth (Gynaecomastia )
• Micropenis - usually small
• Infertility

Question 23

What is an acrocentric chromosome ?

Answer 23

• centromere is located very close to one end of the chromosome.
• short arm.
• look up pic *
• Acrocentric chromes are 13, 14, 15, 21and 22

Chromosomal abnormalities - 2 acrocentric chromosomes get stuck together making on large single chromosome

ex - chromosome 13 can get stuck to chromosome 14.

Carriers of chromosome 21 Robertsonian translocations have an increased risk of miscarriages and familial Down syndrome

Question 24

What does mosaic mean ?

Answer 24

mixed population of trisomy cells and normal cells.