Postnatal Testing

Clinical Indications:

  • Developmental Delay/ Intellectual Impairment (DD/ID)
  • Autism/Autism Spectrum Disorder (ASD)
  • Multiple congenital anomalies (MCA), with or without dysmorphic features
  • Unexplained Seizure Disorder
  • Progressive Disability
  • Cerebral palsy
  • Fragile X syndrome
  • Hearing loss
  • Psychiatric Illness
  • Neuromuscular deterioration
  • Attention deficit Hyperactivity disorder
  • Pervasive Development Disorder (PDD)
  • Duchene Muscular Dystrophy (DMD)
  • Speech delay
  • Apparently syndromic Developmental Delay (DD)/Intellectual Disability (ID)

Studies have suggested that patients with ASD and up to 40 percent of those with DDs/ID may have a genetic etiology for the disability4.Accurate determination of the cause may provide a developmental prognosis, suggest plans for educational and training programs, help in genetic counselling, and relieve parental guilt.

Conventional Approach

G-banded karyotyping has for many years been the standard first-line test for detection of genetic imbalances in infants or children with characteristics of developmental delay/intellectualdisability or autism spectrum disorder. It allows visualization and analysis of chromosomes for chromosomal rearrangements including genomic gains and losses.

Chromosomal microarray (CMA)

First-line test to aid in the diagnostic evaluation of intellectual disability.

Recommendation: Consensus statement by International Collaboration for Clinical Genomics (ICCG)

CMA should be the first tier test for individuals with developmental disabilities, intellectual disabilities, autism spectrum disorders, or multiple congenital anomalies. CMA testing is also indicated for individuals with seizures and other developmental problems for which a genomic basis is suspected.

Recommendation: American College of Medical Genetics (ACMG) practice guidelines

Cytogenetic microarray (CMA) testing for copy number variation (CNV) is recommended as a first-line test in the initial postnatal evaluation of individuals with the following:

  1. Multiple anomalies not specific to a well-delineated genetic syndrome
  2. Apparently non-syndromic developmental delay/intellectual disability
  3. Autism spectrum disorders.

“With karyotyping, we can see only when pieces of the genome of about 5 million base pairs are missing from a chromosome. With CMA, we can see missing pieces of fewer than 100,000 base pairs.”

AUTOMATED

CMA has less human intervention and evaluates fetal DNA directly unlike karyotyping which is a subjective test that depends solely on the expertise of technician & cytogeneticists and is subject to culture artifact in 50% of cases.

EVALUATION OF FETAL DEMISE OR STILL BIRTH

CMA analysis does not require cultured cells. Viability does not come into play at all –DNA can be extracted from tissue that is not living (from product of conception (POC) samples & still births).

MORE SENSITIVE

CMA can identify submicroscopic abnormalities such as translocations, micro deletion or micro duplications disorders more likely to be associated with later pregnancy losses that are missed by karyotyping.

MORE INFORMATIVE

CMA detects copy number variations or loss of heterozygosity regions in cases of normal karyotypes and abnormal / normal ultrasound findings.

FASTER TURN AROUND TIME

CMA eliminates the need to culture cells, therefore turn around the analysis in 10 days, as opposed to 3 weeks by karyotyping.

HIGHER RESOLUTION

CMA yields greater detection rate and precise location of Copy number variations.

Specimen Type: Blood

Specimen requirements: Draw blood in EDTA (purple-top) or Sodium Heparin (green-top) tubes.

Infants 2yrs: 3-5 ml blood

Storage and shipping: Store samples at room temperature before shipping. Ship samples within 24hrs of collection at room temperature in an insulated container and by overnight delivery. In hot weather use ice pack for shipping of blood.

Specimen Type: DNA

Specimen requirements: At least 5 micrograms of DNA in TE (10 mM Tris-cl pH 8.0, 1mM EDTA), or water at ~100 ng/ul concentration. DNA sample extracted using a column based method (Qiagen) or bead-based technology is preferred.

Specimen Type: Tissue (Fresh frozen)

Specimen requirements: Fresh frozen tissue accepted. Please contact us for details. Fixed, paraffin embedded samples are not accepted.

Specimen Type: Cultured Cells

Specimen requirements: Ship at least two T25 flasks of confluent cells.

Storage and shipping: T25 flasks need to be shipped in appropriate complete culture medium filled to the brim. Ship T25 flasks at room temperature in an insulated container once 90% confluency is reached and by overnight delivery.

1. HM Kearney et. al.  American College of Medical Genetics recommendations for the design and performance expectations for clinical genomic copy number microarrays intended for use in the postnatal setting for detection of constitutional abnormalities. Genet Med 2011; 13(7):676–679.

http://www.nature.com/gim/journal/v13/n7/full/gim92011109a.html

2. DT Miller et. al. Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies. Am J Hum Genet 2010; 86(5):749–764.

http://www.cell.com/ajhg/pdf/S0002-9297(10)00208-9.pdf

3. M Manning et. al. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010; 12(11):742–745.

http://www.nature.com/gim/journal/v12/n11/full/gim2010122a.html

4. A Rauch et. al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A. 2006 Oct 1;140(19):2063-2074.

http://www.researchgate.net/profile/Franz_Rueschendorf/publication/6869968_Diagnostic_yield_of_various_genetic_approaches_in_patients_with_unexplained_developmental_delay_or_mental_retardation/links/0fcfd510633362c72f000000.pdf

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