C - case reports

whats the practice guidelines for cyto analysis

established by CCMG

count and sex 10 metaphases

• fully analyze (band for band) 3 cells

• karyogram 2 metaphases (on top of the 3 analyzed)

• 5 cell images submitted in total per case

  • examen 5 for simple cases: confirmation of molecular test, studies on family members to exclude rearrangement

  • more than 10 when suspected mosaicism (extra cells are counted, sexed and checked for chrom of interest

• make sure band resolution meets or exceeds the minimum expectation for the clinical indication

explain the reason for referral → recurrent miscarriages

spontaneous loss is very common (most before recognition) mostly due to aneuploidy

recurrent loss (or recurrent pregnancy loss of habitual abortion) is more rare

• = 3 or more pregnancy losses (some local guides = 2)

about half of cases will have a causative factor

• non genetic causes:

  • uterine anomalies (fibroids, anatomical defects)

  • endocrine disorders (thyroid disease)

  • autoimmune diseases (lupus)

  • thrombophilia (increased blood clots)

• genetic causes:

  • balancecd structural abnormality

  • most common = reciprical and robertsonian translocations

  • less common = inversions

  • parents are phenotypically normal → increassed risk when gamete involved is unbalanced

  • less studied/recognized = single gene defects

if balanced rearangement → 4 options (not able to calculate mendelian/predictable chances of each)

• non viable pregnancy → loss

• child with normal chroms

• child with abnormal but balanced chroms

• live birth with congenital malformations and intellectual disability

explain the reason for referral → infertility

= lack of conception after a reasonable period of sexual intercourse without contraception (usually over 1 year)

primary infertility = never conceived

secondary infertility = at least 1 previous successful conception

non genetic causes:

• having an STI

• anatomical problems (fibroids, polyps, tube blocage)

• endometriosis

• hormonal imbalances

• poor sperm quality, low count or lack of sperm

• past cancer treatments

• tabacco or alcohol use

• being under or over weight

genetic causes:

• sex chrom aneuploidy (including mosaicisms) (klinefelter and turner syndrom)

• balanced structural abnormality → very early loss but looks like infertility

• small changes in genes that control fertility (Y chrom microdeletions in the AZF)

• germline of gonadal mosaicism

explain the internal cytogenetics report

formal documents from the lab to the physician

includes case/patient info, summary of testing/analysis, ISCN, interpretation, limitations, and recommendations

goal = provide clear concise and accurate answer to the clinical question

must be approved by cinical cytogeneticist/lab director

parts of the internal cyto reports

header

• identifies the case

• transcribed from the req

• includes reason for referral

banding method

• select the banding method

• record the vancouver method band resolution result

Analysis

• number of metaphases only analyzed and number karyogramed

  • compare with regulation standards

• analysis notes (not typically included but we add for learning)

  • includes consistent/significant polymorphisms

  • mention atypical cells (single cell abnormalities , cultural artefacts)

result

• gender (control step)

  • left blank if sex cannot be assessed

• final karyotype with proper ISCN

interpretation

• select normal or abnormal result in a male or female patient (or just patient)

• demonstrate understanding of the ISCN, how it relates to the patient and the reason for referral

• no stats, resources, excessive details… → we want clear and concise

limitations

• legal disclaimers that the patient should understand

• some are always included

  • does not detect small abnormalities

  • cant exclude low level mosaicism

recommendations

• help the clinician determine if they need more genetic testing

• must be specific and realistic

• only make recommendations for the patient

• 
  

CCMG retention guidelines (and why)

specimens and analysis records need to be retained for

• legal issues (wrongful dioagnosis)

• investigate potential lab error or quality issue

• family studies

• disease monitoring

• reagent validation/control

• research, presentations, rounds

rentention guidelines

• original specimen (like blood) = until it is verified that metaphases are available for analysis

• cell pellet = 2 weeks after final report is released

• stained GTG slides = 2 years

• images and final reports = 20 years