World Fragile X day 22 nd July

Fragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities, ataxia (after 50 years of age) and cognitive impairment.

  • Males are more severely affected by this disorder than females.
  • Fragile X syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females.
  • Fragile X syndrome is inherited in an X-linked dominant pattern
  • Fragile X-Associated Diminished Ovarian Reserve and Primary Ovarian Insufficiency (4-5%)
  • Family history with mental retardation especially in males
  • Females with Premature ovarian insufficiency POI (very scant or highly delayed period interval or no period prior to 40 years of age ), with or without diminished ovarian reserve ,(high FSH>10- 15 miu/ml, Low Anti Mullerian Hormone AMH < 1.5 ng/ml , Low Antral Follicular Count AFC follicles between 2-9mm ,in both ovaries combined ,of < 7 in number ) should be offered testing , using the PCR DNA blood test If this is positive , the patient can be offered preimplantation genetic testing or prenatal diagnosis) , thus preventing the conception of affected children .

Reproductive Genetics Services at BAUFICI Genetic Laboratory now available

Pre-Conception level testing:

  • a. Individual blood PCR test for
    Fragile x syndrome/
    Duchene muscular dystrophy(DMD)
    Spinal muscular atrophy(SMA) are available .

    Sample collection method: blood samples from couples in lavender colour PCR tube

  • b. Carrier screening for Common genetic diseases in couples before planning a natural pregnancy or ART treatments. This include :

    Thalassemia HBB Globin gene testing
    Sickle cell Anemia
    Duchenne’s Muscular dystrophy (DMD)
    Spinal muscular atrophy ( SMA)
    Fragile X syndrome- repeated expansion disorder testing
    Exome screening covering the entire genome

    Sample collection method: blood samples from couples in lavender colour PCR tube

  • c. Preimplantation Genetic testing for Aneuploidy(PGT A), Balanced translocations(PGT SR), Monogene defects( PGT M)

    • 1.PGT A- For couples with recurrent misscarraiges, recurrent IVF failures, age > 35 years ,elective single embryo transfer
    • 2.PGT SR- either couple carrier of any translocations or inversions and had recurrent pregnancy failures
    • 3.PGT M- ideal for couples with a family history of a genetically affected child or have an indexed child affected with any genetic condition

      Sample Collection method :

      • a. Blastocyst biopsy of Trophectoderm Cells TE can be shipped in cold temperature preferably -20 degrees Genetic counselling must for all the PGT Cases and embryo
      • b. For the first time in India, we offer Non invasive pre implanantion genetic testing ni pGTa for aneuploidy using a new malbac technology PCR amplification of DNA that has leaked out of the embryo , into the spent culture media . This test has concordance rate of 50 to 80 % . It is not as accurate as the standard Embryo biopsy + PGTa on Blastocyst . However it can very effectively grade and prioritize the embryo to be transferred , thus providing the highest chance of implantation & pregnancy , and the lowest chance of miscarriage .

C) Post conceptional Genetic testing

  • a. Non invasive prenatal testing (NIPT)-
    Chromosome screening mainly for trisomy 21, 18,13 and any sex chromosomal abnormalities . Ideal for twin pregnancies, surrogate pregnancy, donor pregnancies. Fetal fraction will also be provided.
    Collection method: 10 ml maternal blood in streck tube
  • b. Product of conceptus testing (POC)-
    POC testing provides aneuploidy information of the aborted fetus. Maternal contamination (common in karyotyping) check also available at our lab which provides high accuracy for testing. Testing is NGS based and there are no chances of cell culture failure (common in karyotyping). Information on all the 23 pairs of chromosomes will be provided
    Sample collection: Tissue sample from fetus dipped in normal saline

American College of OBGYN Recommendations for Genetic screening 2017:

  • Ethnic-specific, pan-ethnic, and expanded carrier screening are acceptable strategies for pre-pregnancy and prenatal carrier screening. Each obstetrician–gynecologist or other healthcare provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening.
  • If a patient requests a screening strategy other than the one used by the obstetrician–gynecologist or other healthcare provider, the requested test should be made available to her after counseling on its limitations, benefits, and alternatives.
  • All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies. Fragile X premutation carrier screening is recommended for women with a family history of fragile X–related disorders or intellectual disability suggestive of fragile X syndrome, or women with a personal history of ovarian insufficiency. Additional screening also may be indicated based on family history or specific ethnicity.
  • Couples with consanguinity should be offered genetic counseling to discuss the increased risk of recessive conditions being expressed in their offspring and the limitations and benefits of carrier screening.
  • Carrier screening will not identify all individuals who are at risk of the screened conditions. Patients should be counseled regarding residual risk with any test result.
  • Prenatal carrier screening does not replace newborn screening, nor does newborn screening diminish the potential benefit of prenatal carrier screening.
  • If a woman is found to be a carrier for a specific condition, her reproductive partner should be offered screening to provide accurate genetic counseling for the couple with regard to the risk of having an affected child. Additional genetic counseling should be provided to discuss the specific condition, residual risk, and options for prenatal testing.
  • If a carrier couple (ie, carriers for the same condition) is identified before pregnancy, genetic counseling is encouraged so that reproductive options (eg, donor gametes, pre-implantation genetic diagnosis, prenatal diagnosis) can be discussed.
  • Individuals with a family history of a genetic disorder may benefit from the identification of the specific familial mutation or mutations rather than carrier screening. Knowledge of the specific familial mutation may allow for more specific and rapid prenatal diagnosis.
  • Given the multitude of conditions that can be included in expanded carrier screening panels, the disorders selected for inclusion should meet several of the following consensus-determined criteria: have a carrier frequency of 1 in 100 or greater, have a well-defined phenotype, have a detrimental effect on quality of life, cause cognitive or physical impairment, require surgical or medical intervention, or have an onset early in life. In addition, screened conditions should be able to be diagnosed prenatally and may afford opportunities for antenatal intervention to improve perinatal outcomes, changes to delivery management to optimize newborn and infant outcomes, and education of the parents about special care needs after birth.
  • Carrier screening panels should not include conditions primarily associated with a disease of adult onset.

ACOG notes that these recommendations are not a substitute for other important routine testing, including newborn screening, and they do not identify all individuals who are at risk of a condition.

References

1.Committee Opinion No. 690 Summary: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol.
March 2017