Neuronal Migration Disorder Panel

Last modified: Mar 21, 2018


  • Is a 58 gene panel that includes assessment of non-coding variants
  • Is ideal for patients with a clinical suspicion of neuronal migration disorder.

Analysis methods

  • PLUS
  • SEQ


3-4 weeks

Number of genes


Test code


CPT codes

SEQ 81405
SEQ 81406
SEQ 81407
DEL/DUP 81479


The Blueprint Genetics Neuronal Migration Disorder Panel (test code MA2601):

  • Is a 58 gene panel that includes assessment of selected non-coding disease-causing variants
  • Is available as PLUS analysis (sequencing analysis and deletion/duplication analysis), sequencing analysis only or deletion/duplication analysis only

ICD codes

Commonly used ICD-10 code(s) when ordering the Neuronal Migration Disorder Panel

ICD-10 Disease
Q04.3 Neuronal migration disorder

Sample Requirements

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 3μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

Neuronal migration disorders (NMDs) are a group of birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. During development, neurons must migrate from the areas where they are originate to the areas where they will settle into their proper neural circuits. The structural abnormalities found in NMDs include schizencephaly, porencephaly, lissencephaly, agyria, macrogyria, polymicrogyria, pachygyria, microgyria, micropolygyria, neuronal heterotopias, agenesis of the corpus callosum, and agenesis of the cranial nerves. Mutations of many genes are involved in neuronal migration disorders, such as DCX in classical lissencephaly spectrum, TUBA1A in microlissencephaly with agenesis of the corpus callosum, and RELN and VLDLR in lissencephaly with cerebellar hypoplasia. Mutations in ARX cause a variety of phenotypes ranging from hydranencephaly or lissencephaly to early-onset epileptic encephalopathies, including Ohtahara syndrome and infantile spasms or intellectual disability with no brain malformations.

Genes in the Neuronal Migration Disorder Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
ACTB* Baraitser-Winter syndrome AD 38 27
ACTG1* Deafness, Baraitser-Winter syndrome AD 21 43
ADGRG1 Polymicrogyria, bilateral frontoparietal, Polymicrogyris, bilateral perisylvian AR 25 30
AKT3 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome AD 12 22
ARFGEF2 Heterotopia, periventricular AR 7 12
ARX Lissencephaly, Epileptic encephalopathy, Corpus callosum, agenesis of, with abnormal genitalia, Partington syndrome, Proud syndrome, Hydranencephaly with abnormal genitalia, Mental retardation XL 64 85
ATP6V0A2 Cutis laxa, Wrinkly skin syndrome AR 16 53
B3GALNT2 Muscular dystrophy-dystroglycanopathy AR 11 13
COL4A1 Schizencephaly, Anterior segment dysgenesis with cerebral involvement, Retinal artery tortuosity, Porencephaly, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, Brain small vessel disease AD 46 97
COL4A2 Hemorrhage, intracerebral AD 11 11
DCX Lissencephaly, Subcortical laminal heterotopia XL 126 138
DYNC1H1 Spinal muscular atrophy, Charcot-Marie-Tooth disease, Mental retardation AD 49 60
EMX2 Schizencephaly AD 4 6
FAT4 Van Maldergem syndrome 2 AR 13 22
FH Hereditary leiomyomatosis and renal cell cancer AD/AR 142 174
FKTN Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle) AD/AR 34 53
FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects XL 102 220
FLVCR2 Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome AR 9 16
GMPPB Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), Limb-girdle muscular dystrophy-dystroglycanopathy AR 13 29
GPSM2 Deafness, Chudley-McCullough syndrome AR 14 11
ISPD Muscular dystrophy-dystroglycanopathy AR 23 44
KATNB1 Lissencephaly 6, with microcephaly AR 6 10
KIF1BP Goldberg-Shprintzen megacolon syndrome AR 6 10
KIF7 Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova syndrome, Joubert syndrome AR/Digenic 15 40
L1CAM Mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome, Hydrocephalus due to congenital stenosis of aqueduct of Sylvius, Spastic, CRASH syndrome, Corpus callosum, partial agenesis XL 57 286
LAMA2 Muscular dystrophy, congenital merosin-deficient AR 90 256
LAMB1 Lissencephaly 5 AR 5 4
LAMC3 Cortical malformations, occipital AR 4 15
LARGE Muscular dystrophy-dystroglycanopathy AR 15 25
MED12 Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndrome XL 24 26
MEF2C Mental retardation AD 31 71
MPDZ Hydrocephalus, nonsyndromic, autosomal recessive 2 AR 7 22
NDE1 Microhydranencephaly, Lissencephaly AR 12 13
NSDHL Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome), CK syndrome XL 15 28
OCLN*,# Pseudo-TORCH syndrome 1 (Band-like calcification with simplified gyration and polymicrogyria) AR 11 15
PAFAH1B1 Lissencephaly, Subcortical laminar heterotopia AD 114 165
PHGDH Neu-Laxova syndrome 1 AR 12 19
PIK3CA* Cowden syndrome, CLOVES AD 83 46
PIK3R2 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 AD 8 6
POMGNT2 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 AR 4 9
POMT1 Muscular dystrophy-dystroglycanopathy AR 34 85
RAB3GAP1 Warburg micro syndrome AR 17 62
RAB3GAP2# Warburg micro syndrome, Martsolf syndrome AR 10 11
RAB18# Warburg micro syndrome 3 AR 5 5
RELN Lissencephaly, Epilepsy, familial temporal lobe AD/AR 20 38
RTTN Microcephaly, short stature, and polymicrogyria with or without seizures AR 11 8
SEPSECS Pontocerebellar hypoplasia, type 2D AR 7 14
SRPX2 Rolandic epilepsy, mental retardation, and speech dyspraxia XL 1 3
TMEM5 Muscular dystrophy-dystroglycanopathy AR 8 7
TUBA1A* Lissencephaly AD 59 64
TUBA8 Polymicrogyria with optic nerve hypoplasia AR 1 1
TUBB2A*,# Cortical dysplasia, complex, with other brain malformations 5 AD 10 4
TUBB2B*,# Polymicrogyria, asymmetric AD 20 30
TUBB3* Fibrosis of extraocular muscles, congenital, Cortical dysplasia, complex, with other brain malformations AD/AR 27 24
TUBG1* Cortical dysplasia, complex, with other brain malformations 4 AD 4 3
VLDLR Cerebellar ataxia, mental retardation, and dysequilibrium syndrome AR 9 24
WDR62 Microcephaly AR 30 44
YWHAE Distal 17p13.3 microdeletion syndrome, Endometrial stromal sarcoma, 17p13.3 microduplication syndrome, Miller-Dieker syndrome AD/AR 12 42

* Some, or all, of the gene is duplicated in the genome. Read more.

# The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads).

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#)

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Orphanet databases.

Non-coding variants covered by the panel

Gene Genomic location HG19 HGVS RefSeq RS-number
ADGRG1 Chr16:57673285 c.-435_-421delCAACGGTTGCCAGGG NM_001145774.1
COL4A1 Chr13:110802679 c.*31G>T NM_001845.4
COL4A1 Chr13:110802678 c.*32G>T NM_001845.4
COL4A1 Chr13:110802675 c.*35C>A NM_001845.4
FKTN Chr9:108368857 c.648-1243G>T NM_006731.2
L1CAM ChrX:153133652 c.1704-75G>T NM_000425.4
L1CAM ChrX:153131293 c.2432-19A>C NM_000425.4
L1CAM ChrX:153128846 c.3531-12G>A NM_000425.4
L1CAM ChrX:153136500 c.523+12C>T NM_000425.4
LAMA2 Chr6:129636608 c.3556-13T>A NM_000426.3 rs775278003
LAMA2 Chr6:129714172 c.5235-18G>A NM_000426.3 rs188365084
POMT1 Chr9:134379574 c.-30-2A>G NM_007171.3
TUBA8 Chr22:18604221 c.4-21_4-8delGTTGCTTCCCTCTC NM_018943.2
YWHAE Chr17:1303862 c.-458G>T NM_006761.4

Added and removed genes from the panel

Genes added Genes removed

Test strength

The strengths of this test include:
  • CAP and ISO-15189 accreditations covering all operations at Blueprint Genetics including all Whole Exome Sequencing, NGS panels and confirmatory testing
  • CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
  • Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
  • Careful construction of clinically effective and scientifically justified gene panels
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • Our publically available analytic validation demonstrating complete details of test performance
  • 1479 non-coding disease causing variants in Blueprint WES assay (please see below ‘Non-coding disease causing variants covered by this panel’)
  • Our rigorous variant classification based on modified ACMG variant classification scheme
  • Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
  • Our comprehensive clinical statements

Test limitations

The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: OCLN (5, 7, 8), RAB3GAP2 (8, 9, 17, 18, 21, 27, 28, 30, 32, 34), RAB18 (6). Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene's target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:
  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).

This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

The Blueprint Genetics neuronal migration disorder panel covers classical genes associated with neuronal migration disorder. The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sliced from our high-quality whole exome sequencing data. Please see our sequencing and detection performance table for different types of alterations at the whole exome level (Table).

Assays have been validated for different starting materials including EDTA-blood, isolated DNA (no FFPE), saliva and dry blood spots (filter card) and all provide high-quality results. The diagnostic yield varies substantially depending on the assay used, referring healthcare professional, hospital and country. Blueprint Genetics' Plus Analysis (Seq+Del/Dup) maximizes the chance to find a molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be a cost-effective first line test if your patient's phenotype is suggestive of a specific mutation type.

Performance of Blueprint Genetics Whole Exome Sequencing (WES) assay. All individual panels are sliced from WES data.

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide variants 99.65% (412,456/413,893) >99.99%
Insertions, deletions and indels by sequence analysis
1-10 bps 96.94% (17,070/17,608) >99.99%
11-50 bps 99.07% (957/966) >99.99%
Copy number variants (exon level dels/dups)
Clinical samples (small CNVs, n=52)
1 exon level deletion 92.3% (24/26) NA
2 exons level deletion/duplication 100.0% (11/11) NA
3-7 exons level deletion/duplication 93.3% (14/15) NA
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb) 100% (37/37)
Simulated CNV detection
2 exons level deletion/duplication 90.98% (7,357/8,086) 99.96%
5 exons level deletion/duplication 98.63% (7,975/8,086) 99.98%
The performance presented above reached by WES with the following coverage metrics
Mean sequencing depth at exome level 174x
Nucleotides with >20x sequencing coverage (%) 99.4%


The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases such as, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as SIFT, PolyPhen, MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, the customer has an access to details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with inadequate coverage if present. This reflects our mission to build fully transparent diagnostics where customers have easy access to crucial details of the analysis process.

Clinical interpretation

We provide customers with the most comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists, medical geneticists and clinical consultants prepare the clinical statement together by evaluating the identified variants in the context of the phenotypic information provided in the requisition form. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals regardless of whether they have formal training in genetics.

Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the Blueprint Genetics Variant Classification Schemes based on the ACMG guideline 2015. Minor modifications were made to increase reproducibility of the variant classification and improve the clinical validity of the report. Our experience with tens of thousands of clinical cases analyzed at our laboratory allowed us to further develop the industry standard.

The final step in the analysis of sequence variants is confirmation of variants classified as pathogenic or likely pathogenic using bi-directional Sanger sequencing. Variant(s) fulfilling all of the following criteria are not Sanger confirmed: 1) the variant quality score is above the internal threshold for a true positive call, 2) an unambiguous IGV in-line with the variant call and 3) previous Sanger confirmation of the same variant at least three times at Blueprint Genetics. Reported variants of uncertain significance are confirmed with bi-directional Sanger sequencing only if the quality score is below our internally defined quality score for true positive call. Reported copy number variations with a size <10 exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen less than three times at Blueprint Genetics.

Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references used, congress abstracts and mutation databases to help our customers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.

Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification within the family. In the case of variants of uncertain significance (VUS), we do not recommend family member risk stratification based on the VUS result. Furthermore, in the case of VUS, we do not recommend the use of genetic information in patient management or genetic counseling. For eligible cases, Blueprint Genetics offers a no charge service to investigate the role of reported VUS (VUS Clarification Service).

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Thus, our database, and our understanding of variants and related phenotypes, is growing by leaps and bounds. Our laboratory is therefore well positioned to re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.