La creación del Consejo de la Judicatura en Ecuador

El gobierno de la Función Judicial: origen del Consejo de la Judicatura

2.2 Reforma de la justicia y Consejo de la Judicatura en Ecuador

2.2.2 La creación del Consejo de la Judicatura en Ecuador

Procedure(s) covered by this policy: Procedure Code(s) Requires: Prior- authorization* Lab Procedure Restrictions† Chromosomal Microarray [BAC],

Constitutional 81228 Yes No

Chromosomal Microarray [SNP],

Constitutional 81229 Yes No

Chromosomal Microarray [FISH],

Constitutional 88271 Not Covered Not Covered

* - Clinical Review necessary prior to authorization for this procedure.

† - Lab procedures require specified sequence to be followed and additional information is required to be supplied by lab performing procedure(s).

What Are Copy Number Variants in Developmental Disorders?

• Intellectual disability (ID) and congenital birth defects affect approximately 3-4% of the general population.1 Major structural birth defects can often be identified prenatally by ultrasound evaluation, while some minor anomalies and ID cannot.2 • The etiology of congenital anomalies is complex. Some developmental problems

may be caused by environmental factors, such as injury and infection. However, genetic causes also play a significant role.1,2

• Routine chromosome analysis (karyotyping) by chorionic villus sampling (CVS) or amniocentesis has historically been a first-line test in the evaluation of a pregnancy identified with congenital birth defects.2

• However, small deletions and duplications of genetic material account for a significant proportion of developmental disorders without a clear etiology based on clinical findings.1 These changes are called "copy number variants" (CNVs). CNVs are detected using chromosomal microarray (CMA) testing. CMA is known by several names including array-comparative genomic hybridization (aCGH) and single-nucleotide polymorphism arrays (SNP-array).1

• Chromosomal microarray on chorionic villi or amniocytes is indicated in a

pregnancy identified with one or more major structural abnormalities. Identifying an underlying genetic cause in these patients may:2

o Provide diagnostic and prognostic information o Guide prenatal management and decision-making

o Allow for testing of family members and accurate recurrence risk counseling

• If a unique CNV is detected in a fetus, it is usually necessary to test both parents to determine whether the CNV is inherited or a new (de novo) genetic change. This information along with parental findings can be used to weigh the

possibilities of a benign vs. pathogenic variant. However, even with parental

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studies, the clinical outcome may remain unclear.5 A de novo variant is more likely to represent a pathologic abnormality.5,6

Test Information

• Chromosomal microarray (CMA) testing generally works by fluorescently tagging DNA from a patient test sample with one color and combining it with a control sample tagged in a different color. The two samples are mixed and then added to the array chip, where they compete to hybridize with the DNA fragments on the chip. By comparing the test sample versus the control, computer analysis can determine where genetic material has been deleted or duplicated in the patient. • There are a growing number of CMA testing platforms, including non-chip based

applications, which differ in approach and resolution. Testing guidelines do not endorse one CMA over another.2,4 However, international consensus guidelines do suggest that CMAs should have coverage better than that offered by a standard karyotype (~5 Mb), and resolution of ≥400 kb throughout the genome.4

• CMAs include the subtelomeric regions and all known chromosome

microdeletion syndrome regions, such as those for 22q11.2 (DiGeorge) syndrome, Williams syndrome (7p11.2), and Smith-Magenis syndrome (17p11.2). Therefore, subtelomeric and disease-specific FISH tests are not needed in parallel with CMA, or as follow-up to normal CMA results.

• In contrast to typical chromosome analysis, CMA testing does not require dividing cells in culture. This makes testing possible in samples that may be difficult to culture, such as those from perinatal losses. 5,6

• While there are significant advantages of CMA over conventional karyotyping with regard to resolution and yield, there are disadvantages as well. Limitations of CMA include the inability to detect 1) balanced translocations or inversions, 2) certain forms of polyploidy, 3) low level mosaicism, and 4) some marker

chromosomes. Additional disadvantages of CMA include the detection of CNVs of uncertain clinical significance, the inability to differentiate free trisomies from unbalanced Robertsonian translocations, and the high cost of testing as

compared to traditional karyotyping.2

Guidelines and Evidence

• The American College of Obstetricians and Gynecologists Committee on Genetics and the Society for Maternal-Fetal Medicine (2013) published a joint committee opinion regarding the application of chromosomal microarray in the prenatal setting. This opinion recommended that CMA replaces fetal kayotyping for “patients with a fetus with one or more major structural anomalies identified on ultrasonographic examination and who are undergoing invasive prenatal diagnosis”.5

• Diagnostic yield of CMA testing differs based on clinical presentation. The results of one recent multicenter trial of CMA in the prenatal setting were published in 2012. This study reported that CMA identified a clinically relevant deletion or duplication in 6% of prenatal cases with a structural anomaly and normal

Lab Management Guidelines V1.0.2016

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karyotype. In addition, 1.7% of prenatal cases with an indication of advanced maternal age or positive screening results and normal karyotype had a clinically relevant deletion or duplication identified by CMA.3

• In a large series of fetuses with ultrasound anomalies and normal conventional karyotype, CMA detected chromosome abnormalities in 5% of fetuses and up to 10% in those with 3 or more anatomic abnormalities.2

Criteria

• Genetic Counseling:

o Pre- and post-test genetic counseling by an appropriate provider (as deemed by the Health Plan policy), AND

• Previous Genetic Testing:

o No previous chromosomal microarray testing in the same pregnancy, AND • Diagnostic Prenatal Testing:‡

o The member has sufficient risk of fetal CNV to justify invasive prenatal diagnosis. [It is important to note that invasive diagnostic procedures such as chorionic villus sampling and amniocentesis are associated with risks; the provider and patient must have determined that the associated

benefits outweigh the risks.]

‡

Microarray may also be used in association with in utero fetal demise, stillbirth, or neonatal death. If microarray will be performed on fetal tissue after delivery, reference the developmental disorders policy.

Exclusions and Other Considerations:

• If routine karyotype and CMA are ordered simultaneously, only the most appropriate test based on clinical history will be considered for coverage. • Full karyotype in addition to CMA is considered excessive in the prenatal

diagnosis setting. However, a limited 5 cell analysis will be approved in addition to CMA if criteria for CMA are met. This approval will be subject to claims review to ensure that the appropriate number of units for a limited 5 cell analysis is billed.

• If CMA has been performed, the following tests are often excessive and are not considered medically necessary. Each test may require prior authorization or medical necessity review during the claims process.

o Routine karyotype o FISH analysis o Telomere analysis

o More than one type of microarray analysis (i.e. if 81228 performed, 81229 is not medically necessary)

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References

1. Manning M, Hudgins L; for the Professional Practice and Guidelines Committee. American College of Medical Genetics Practice Guidelines: Use of array-based technology in the practice of medical genetics. Genet Med. 2007;9(9):650-3.

2. Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013 May;15(5):399-407. doi: 10.1038/gim.2013.32. Epub 2013 Mar 21. Available at https://www.acmg.net/docs/pp-g-ASD-schaffer-aop-gim201332a.pdf. 3. Shaffer LG; American College of Medical Genetics Professional Practice and Guidelines

Committee. American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation. Genet Med. 2005;7:650-4. 4. Manning M, Hudgins L; for the Professional Practice and Guidelines Committee. American

College of Medical Genetics Practice Guidelines: Array-based technology and

recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med. 2010;12(11);742-5. Available at

http://www.acmg.net/StaticContent/PPG/Array_based_technology_and_recommendations_fo r.13.pdf.

5. Miller DT, Adam MP, Aradhya S, 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):749-64.

6. Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JP, Burton H. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med. 2009 Mar;11(3):139-46.

7. Hochstenbach R, van Binsbergen E, Engelen J, et al. Array analysis and karyotyping: workflow consequences based on a retrospective study of 36,325 patients with idiopathic developmental delay in the Netherlands. Eur J Med Genet. 2009 Jul-Aug;52(4):161-9. 8. Miles JH, McCathren RB, Stichter J, Shinawi M. Autism Spectrum Disorders (Updated April

13, 2010). In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2014. Available at http://www.ncbi.nlm.nih.gov/books/NBK1442/.

9. Warren JE, Turok DK, Maxwell TM, Brothman AR, Silver RM. Array comparative genomic hybridization for genetic evaluation of fetal loss between 10 and 20 weeks of gestation.

Obstet Gynecol. 2009 Nov;114(5):1093-102.

10. American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013 Dec;122(6):1374-7. doi:

10.1097/01.AOG.0000438962.16108.d1.

11. Regier DA, Friedman JM, Marra CA. Value for money? Array genomic hybridization for diagnostic testing for genetic causes of intellectual disability. Am J Hum Genet. 2010;86:765- 72.

Lab Management Guidelines V1.0.2016

Chromosome Analysis for Blood, Bone

In document Los modelos de integración del Consejo de la Judicatura y su relación con la independencia del Poder Judicial (página 72-78)