Megalencephaly Panel

General Information

Lab Name

Lab Code

MEGPX

Epic Ordering

Megalencephaly Panel

Description

Megalencephaly Panel is useful for the evaluation of patients with a suspected megalencephaly syndrome. The panel uses next- generation sequencing to detect most mutations in ABCC9, AKT1, AKT2, AKT3, BRAF, BRWD3, CCND2, CDKN1C, CHD8, CRADD, CSF1R, CTNNB1, DEPDC5, DNMT3A, EED, EZH2, FGFR1, FLT4, GATA2, GLI3, GNA11, GNAQ, GNAS, GPC3, HEPACAM, HRAS, IDH1, IDH2, KCNJ8, KRAS, MAP2K1, MED12, MET, MTOR, NPRL2, NPRL3, NRAS, NSD1, PDGFRB, PIK3CA, PIK3R2, PTCH1, PTEN, PTPN11, RASA1, SETD2, SMAD4, STRADA, TSC1, TSC2. The assay completely sequences all exons of these genes AND detects large deletions, duplications and mosaicism.

Genes Tested

Gene	Disease	Reference (PMID)
ABCC9	Cantu syndrome	22610116
AKT1	Proteus syndrome	21793738,22876373
AKT2	Asymmetric overgrowth with hypoglycemia	21979934
AKT3	Hemimegalencephaly, Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, focal cortical dysplasia	22729224,25722288
BRWD3	X-linked intellectual disability and macrocephaly	17668385
CCND2	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome	24705253
CDKN1C	IMAGe syndrome, Beckwith Wiedemann	20301568,24624461
CHD8	Intellectual developmental disorder with autism and macrocephaly	31721432, 31980904
DEPDC5	Focal epilepsy with or without focal cortical dysplasia, familal focal epilepsy with variable foci	23542701,23542697
DNMT3A	Tatton-Brown-Rahman Syndrome	24614070
EED	Overgrowth and macrocephaly	25787343
EZH2	Weaver syndrome	23865096
GLI3	Greig cephalosyndactyly, Acrocallosal syndrome	20301619,12414818
GNAQ	Sturge Weber Syndrome, capillary malformation (port-wine)	23656586
GNAS	Fibrous Dysplasia/McCune-Albright Syndrome, Pseudopseudohypoparathyroidism, pseudohypoparathyroidism 1A, 1B, and progressive osseous heterotopia	25719192
GPC3	Simpson-Golabi-Behmel syndrome	20301398
KCNJ8	Cantu syndrome	24700710
MED12	Opitz-Kaveggia syndrome	20301719
MTOR	Megalencephaly, hemimegalencephaly, focal cortical dysplasia	25799227
NPRL2	Epilepsy, familial focal, with variable foci 2	26505888, 27173016
NPRL3	Epilepsy, familial focal, with variable foci 3	26285051 35136953
NSD1	Sotos syndrome	20301652
PIK3CA	PIK3CA-related overgrowth syndromes (PROS), Megalencephaly with capillary malformation (MCAP), CLOVES syndrome, megalencephaly, hemimegalencephaly, focal cortical dysplasia, Klippel Trenauney syndrome, isolated lymphatic malformations, isolated venous malformations	23946963,25681199,22729224,26637981
PTCH1	Nevoid basal cell carcinoma syndrome, Basal Cell Nevus Syndrome, Gorlin syndrome	20301330
PTEN	Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome (BRRS) PTEN related hamartoma syndrome, autism, focal cortical dysplasia	20301661
SETD2	Overgrowth and macrocephaly	24852293
TSC1	Tuberous Sclerosis	20301399
TSC2	Tuberous Sclerosis	20301399

For previous versions of MegaPlex™ - Megalencephaly Panel, see Previous Versions, MEGPX.

References

Pritchard CC, et al. ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 2012, 14:357-66. 22658618
Walsh T, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A 2010, 107:12629-33. 20616022
Nord AS, Lee M, King MC, and Walsh T. Accurate and exact CNV identification from targeted high-throughput sequence data. BMC Genomics 2011, 12:184. 21486468
Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010, 11:31-46. 19997069

Synonyms

ABCC9, AKT1, AKT2, AKT3, autism, BRAF, BRWD3, CCND2, CDKN1C, CHD8, Chiari malformation, CRADD, CSF1R, CTNNB1, DEPDC5, developmental delay, DNMT3A, EED, EZH2, FGFR1, FLT4, GATA2, GLI3, GNA11, GNAQ, GNAS, GPC3, hemihypertrophy, HEPACAM, HRAS, hydrocephalus, IDH1, IDH2, KCNJ8, KRAS, macrocephaly, MAP2K1, MED12, Megaplex, MET, MTOR, next-generation sequencing, NPRL2, NPRL3, NRAS, NSD1, overgrowth syndrome, PDGFRB, PIK3CA, PIK3R2, polydactyly, PTCH1, PTEN, PTPN11, RASA1, seizures SETD2, SMAD4, STRADA, syndactyly TSC1, TSC2, tuberous sclerosis, ventriculomegaly

Components

Code	Name
MEGGS	Megalencephaly Genes Analyzed
MEGRE	Megalencephaly Panel Result
MEGIN	Megalencephaly Panel Interp
MEGCH	Megalencephaly Panel Clin Hist
MEGMT	Megalencephaly Panel Methods
MEGDI	Megalencephaly Lab Director

Interpretation

Method

Next-generation sequencing.

Sequences are aligned to the human genome reference (hg19). Test performed by targeted capture for listed genes followed by next-generation sequencing with Illumina technology. This test was developed and its performance characteristics were determined by the University of Washington Department of Laboratory Medicine. It has not been cleared or approved by the US Food and Drug Administration. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high-complexity clinical laboratory testing. This test is used for clinical purposes. It should not be regarded as investigational or for research.

Reference Range

See individual components

Ref. Range Notes

No mutations detected.

Guidelines

Next-Generation Sequencing Panels Preauthorization

Ordering & Collection

Specimen Type

Skin biopsy/Cultured fibroblasts, FFPE Tissue, Peripheral Blood, purified DNA

Collection

Preferred:

1. Skin biopsy: 2-4 mm punch biopsy of skin collected under sterile conditions and place in sterile vials with 1-3 mL of transport medium. For specific requirements including preferred transport medium, call cytogenetics laboratory. Do not put biopsy in formaldehyde, formalin, alcohol, 5% dextrose or medium buffered with bicarbonate. Skin biopsies may be routed to cytogenetics for culturing fibroblasts.

For patients within the UW Medicine system: Once biopsy has been obtained, follow instructions for transport of skin biopsies for genetic/molecular testing, see Test catalog entry under Code:599.

2. Formalin-fixed paraffin embedded tissue: Send EITHER (a) formalin-fixed slides, OR (b) formalin-fixed tissue block:

(a) Instructions for slide specimens: 1 slide at 4-micron thickness stained with hematoxylin-and-eosin AND 10 unstained, non-baked slides at 10-micron thickness. Unstained slides can be on charged or uncharged slides. Note: In order to ensure that enough DNA is obtained, the minimum acceptable tissue area is 10 square millimeters when ten 10-micron slides are supplied (1 cubic millimeter of tissue). Tissue sections should contain as much lesional tissue as possible; to ensure detection of all types of mutations, there should be at least 10% lesional cells in the tissue area processed for DNA.

(b) Instructions for tissue block specimen: Provide complete formalin-fixed tissue block containing lesional tissue. If there is more than one tissue block, please provide the block that has the greatest amount of lesional tissue. Tissue block will be returned at completion of testing.

Unacceptable: Decalcified samples; tissue samples treated with fixatives other than formalin.

Also acceptable:

BLOOD:

10 mL whole blood in LAVENDER TOP EDTA or YELLOW TOP ACD tube and purified DNA from peripheral blood or cultured cells.

CULTURED CELLS:

(2) T25 or (1) T75 flask (minimum 1-T25 flask)*.

*Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide Maternal Cell Contamination, Fetal [MCC] for ordering and specimen requirements)

Forms & Requisitions

Requisition Form and Ordering Instructions:

Fill out a Genetics Requisition Form
Check "Megalencephaly Panel"

Genetics Preauthorization Form (preauthorization is only done for providers who are external to the UW system).

Handling Instructions

Ship specimen at room temperature for overnight delivery.

Blood specimens can be held for up to 7 days before shipping if refrigerated.

Ship specimens to:

UW MEDICAL CENTER

LABORATORY MEDICINE - GENETICS LAB

1959 NE PACIFIC ST, ROOM NW220

SEATTLE, WA 98195-7110

Quantity

requested: Entire sample
minimum: For FFPE or skin biopsy, see above. 5 mL whole blood.

Processing

Processing: Blood: Refrigerate whole blood

Unacceptable Conditions: Frozen or clotted specimens

Stability (collection to initiation of testing): Ambient: 5 days; Refrigerated: 7 days; Frozen: Unacceptable

Purified DNA: Refrigerate DNA specimens. Frozen is acceptable.

Performance

LIS Dept Code

Genetics (GEN)

Performing Location(s)

UW-MT	Genetics Attention: Genetics Lab Clinical lab, Room NW220 University of Washington Medical Center 1959 NE Pacific Street Seattle, WA 98195 Tel: 206-598–6429 M–F (7:30 AM–4:00 PM) Fax: 206-616-4584 Lab email: cgateam@uw.edu Tel (EXOME only): 206-543-0459	Faculty Jillian Buchan, PhD, FACMG Runjun Kumar, MD, PhD Regina Kwon, MD, MPH Christina Lockwood, PhD, DABCC, DABMGG Brian Shirts, MD, PhD Abbye McEwen, MD, PhD Colin Pritchard, MD, PhD Vera Paulson, MD, PhD Eric Konnick, MD, MS He Fang, PhD

Frequency

Results within 6 weeks, once sample arrives in the laboratory.

Available STAT?

Billing & Coding

CPT codes
Billing Comments: For additional test/billing information, see following page: MegaPlex™ CPT codes.

For pricing information, contact Client Support Services 206-520-4600 or 800-713-5198.

Billing and Insurance Pre-Authorization

We offer insurance pre-authorization services (preauthorization is only done for providers who are external to the UW system).

Email: gpab@uw.edu or call 1-855-320-4869 for more information.

Genetics Preauthorization Form
LOINC: 51966-0
Interfaced Order Code: UOW2845