Genetic testing

Def: Genetic testing identifies changes in chromosomes, genes, or proteins.

Importance:  can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder.

More than 1,000 genetic tests are currently in use, and more are being developed.

Knowledge of the test result could lead to emotional and social problems in the child, altering both relationships within a family and expectation for the future in a variety of areas such as education, employment, and relationships.

For many types of genetic analysis, a negative test result must be interpreted with caution in case it is a false negative, i.e a genetic abnormality is actually present but was not detected by the test.

Pathological significance of detected genetic alteration may be unclear due to missense mutation and variable expression.

When preforming genetic testing, it is important to be aware that the diagnosis of a genetic disease will not only have implications for the affected individual but may have ramifications for the other family members, who may be at risk of being affected or of being carriers for the condition.

Several methods can be used for genetic testing:

·       Molecular genetic tests (or gene tests): study single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder, it depends on base sequences on chromosome.

ü  Southern blot analysis

ü  The polymerase chain reaction (PCR)

ü  DNA sequencing

ü  Next generation sequencing (NextGen).

·       Cytogenetics: concerned with how the chromosomes relate to cell behavior, particularly to their behavior during mitosis and meiosis include: Karyotyping

·       Molecular cytogenetics: involves the combination of molecular biology and cytogenetics

ü  Fluorescent in situ hybridization (FISH)

ü Comparative genomic hybridization (CGH).

ü Array comparative genomic hybridization (also microarray-based comparative genomic hybridization, matrix CGH, array CGH, aCGH)

·       Biochemical genetic tests study the amount or activity level of proteins; abnormalities in either can indicate changes to the DNA that result in a genetic disorder.

The chromosomes could be sampled from:

˗   Peripheral blood lymphocytes                                     - Bone marrow cells

˗   Skin fibroblast                                                              - Solid tissue cells

˗   Amniotic fluid cells

Medical applications (indications of genetic testing, karyotyping, chromosomal culture, analysis) :

1.     Multiple congenital anomalies:

Birth defects > one developmental regions of the body

A.    Confirmation of a clinical diagnosis

B.    Estimate recurrence risk of future sibling

-Karyotyping.

Karyotyping

Def: studying chromosomes in a form suitable for analysis during metaphase or Chromosomes are stained and visualized under a microscope.

Steps:

1.  As chromosomes are only visible microscopically in dividing cells (metaphase chromosomes)

2.     Chromosome analysis involves taking some non-dividing cells (usually peripheral blood lymphocytes)

3.     Culturing them to encourage cell division on certain media.

4.     Arrest of cellular division in metaphase.

5.     Adding hypertonic saline leading to bursting of cells & release of chromosomes.

6.     Staining which creates unique banding patterns on the chromosomes and subsequently examines the cells under microscopy for any extra or missing chromosomes, or large scale structural chromosomal abnormalities.

This method will miss any changes smaller than 5–10 megabases (5–10 million bases) in size, so is unsuitable for the detection of most microdeletions or duplications.

Along with array comparative genomic hybridization it is helpful in identifying changes in amount of genetic material – gene copy number variation (CNV) including duplications (increased copy number) and deletions (decreased copy number), so they are useful Investigate broad/complex phenotype.

-Fluorescent in situ hybridization (FISH).

Fluorescent in situ hybridization (FISH)

Using Fluorescent-labelled DNA probes which are designed that are complementary to the DNA sequences being assessed, to detect and localize the presence or absence of specific DNA sequence on Chromosome.

Steps:

ü Chromosomes are immobilized and denatured on a microscope slide and exposed to a solution containing a fluorescently labelled probe specific to a specific chromosomal region.

ü After hybridization (the formation of a double strand of DNA from complementary single strands), the slide is washed and examined microscopically.

ü Where the probe has hybridized, fluorescent spots are seen over the relevant chromosome.

For example, if a child were suspected of having 22q11 deletion syndrome, FISH using a 22q11-specific probe would show only one pair of fluorescent spots, rather than two.

Types of FISH probes:

ü  Centromeric (aneuploidy)

ü  Telomeric (subtelomeric rearrangements)

ü  Sequence specific (microdeletions)

ü  Whole chromosome paint (complex rearrangements)

ü  Reverse painting (to identify origin of unidentified chromosomal material)

Useful for microdeletion syndromes.

- Hutchinson’s Triad.

Hutchinson's triad

It is a common pattern of presentation for congenital syphilis.
It consists of :-

1. Interstitial keratitis
2. Hutchinson incisors
3. Eighth nerve deafness.

Dr Ibrahim

Return to other triads here.

-Complications of Tetralogy of fallot.

Complications of Tetralogy of fallot
"Inches"

Infective endocarditis,Low I.Q.
Neurological (e.g Brain abscess,cerebrovascular accidents)
Cyanotic spell,Clubbing.
Hematological(e.g polycythemia,IDA,Thrombosis).
Hyperuracemia and gout,Heart Failure (rare).
Exercise intolerance.
Squatting,scoliosis,Stunted growth.

Dr Ibrahim

-No in ASD.

No in Atrial septal defect.

No murmur due to ASD itself but murmur of relative MS,PS.
No ACEIs if HF occur but give diuretics and digitalis.
No spontanous closure of ASD.
No symptoms or signs in small ASD.

Dr Ibrahim

-Congenital Rubella Syndrome.

Congenital Rubella Syndrome

Aetiology:-
Maternal infection by rubella leads to Maternal viremia which lead to transplacental spread of the virus to the fetus causing fetal viremia whcih in turn leads to infection invloving many fetal organs and hence congenital anomalies.

N.B:- Newborn discharge virus in his secretions for 12-18 months after birth so he is infectious.
Incidence:-
*In the 1st trimester:- 15-20%.
*In the 4th month:- 5%.   

-Factors affecting human linear growth.

Factors affecting human linear growth.

• Age
• Sex
• Race.
• Hereditary factors:- Children of two short parents will probably be short and vice versa.
• Endocrinal factors e.g Growth Hormone which is responsible for stimulation of body growth in humans.
• Nutritional factors:- Adequate nutrients must be available for normal growth.
• General health:- Any serious systemic disease in childhood is likely to reduce growth (e.g. chronic kidney disease or chronic infection).
• Intrauterine growth retardation (small birth weight):-These infants often growpoorly in the long term.
• Emotional deprivation and psychological factors:- These can impair growth by complex, poorly understood mechanisms.
• Chromosomal abnormalities.
• Skeletal maturity.

Dr Ibrahim

- Medical treatment of hydrocephalus.

Medical treatment of hydrocephalus

*Aim:-

Medical treatment is used to delay surgical intervention.

*Medical treatment is not effective in long-term treatment of chronic hydrocephalus. It may induce metabolic consequences and thus should be used only as a temporizing measure.

*Lines of TTT:- "Fair"

• Furosemide:1mg/kg/day.(Decreasing CSF secretion).
• Acetazolamide 5mg/kg/day.(Decreasing CSF secretion).
• Isosorbide (Increasing CSF reabsorption).
• Restriction of water and salts.

Dr Ibrahim

- Skull causes of macrocephaly.

Skull causes of Macrocephaly.

"Oscar"

Osteogenesis imperfecta.
Secondaries especially neuroblastoma.
Chronic hemolytic anemia.
Achondroplasia.
Rickets.

Dr Ibrahim

-Guillain Barré syndrome.

Guillain Barré syndrome

Aetiology(theories):-

• Postinfection:50% of cases have preceding respiratory or GIT viral infection.
• Post vaccination:following vaccination against swine flu virus.
• Lymphoma.
• Autoimmune theory.

Clinical Picture:-
1-Initial febrile illness.
2-Motor affection:-

• Bilateral symmetrical ascending affection of both lower limbs,trunk,upper limbs,Bulbar muscles,facial muscles then diphragm and respiratory muscles.
• The Affection is proximal more than distal in adult.
• The Affection is proximal more than distal in infant and childrens.
• Weakness is associated with hypotonia and areflexia.
  

- Grades in medicine.

Grades in medicine 

In many branches of medicine we meet what is called "grades" this grades were put to classify certain conditions. Here I will put the grades what i had found as they meet me in books in simple way......... so you can share us.

• Grading of Murmurs (click here).
• Grading of Vesicoureteric Reflux (click here).
• Grades of Dyspnea (click here).
• Grades of respiratory distress. (click here).
• Grades of splenomegaly. (click here).
• Grading of hypertensive retinopathy (click here).
• Grades of binocular single vision. (click here).
• Grades for quantitative assessment of muscle power (click here).
• Deep tendon reflex grading (click here).
• Poisoning severity grading (click here).
• Grading of function in rheumataid disease(click here).
•  ASA Grading system (click here).
• Renal trauma grading scale (click here).
• Compound fracture grading- Gustilo-Anderson grading (click here).
• Sperm Motility grading.(click here).
• Wagner Grading System for Diabetic Foot Infections.(click here).
• Savary miller endoscopic grading of GORD.(click here).
• Sher's grading of abruptio placentae.(click here).
• Modified Canadian Cardiovascular Society grading of angina pectoris
• Varicocele grading (click here) 
  

Dr Ibrahim