Brain Malformation Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
12613 ACTB 81479,81479 Order Options and Pricing
ACTG1 81479,81479
ADGRG1 81479,81479
ARFGEF2 81479,81479
ARX 81404,81403
CASK 81479,81479
CHMP1A 81479,81479
CTNNA2 81479,81479
DCX 81405,81479
DYNC1H1 81479,81479
EXOSC3 81479,81479
FKRP 81404,81479
FKTN 81405,81479
FLNA 81479,81479
KATNB1 81479,81479
KIF2A 81479,81479
KIF5C 81479,81479
KIF7 81479,81479
KIFBP 81479,81479
LAMB1 81479,81479
LAMC3 81479,81479
LARGE1 81479,81479
MACF1 81479,81479
NDE1 81479,81479
NEDD4L 81479,81479
OPHN1 81479,81479
PAFAH1B1 81406,81405
POMGNT1 81406,81479
POMT1 81406,81479
POMT2 81406,81479
PQBP1 81405,81404
RAB3GAP1 81479,81479
RAB3GAP2 81479,81479
RARS2 81479,81479
RELN 81479,81479
RTTN 81479,81479
TMTC3 81479,81479
TSEN2 81479,81479
TSEN34 81479,81479
TSEN54 81479,81479
TUBA1A 81479,81479
TUBA8 81479,81479
TUBB 81479,81479
TUBB2A 81479,81479
TUBB2B 81479,81479
TUBB3 81479,81479
TUBG1 81479,81479
VLDLR 81479,81479
VRK1 81479,81479
WDR62 81407,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
12613Genes x (50)81479 81403, 81404, 81405, 81406, 81407, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Brain malformation is a group of complex conditions influenced by both genetic and environmental factors such as chemicals, infections or radiation during pregnancy. This brain malformation panel focuses on important brain malformations including tubulinopathies, cortical dysplasia, cortical malformations, periventricular heterotopia, lissencephaly, polymicrogyria, pontocerebellar hypoplasia, and muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies. Most brain malformations have onset before birth. The symptoms vary with different causes. For example, in tubulinopathies, the major features include lissencephaly, pachygyria, cortical dysplasia, simplified gyral pattern, microlissencephaly, abnormality of corpus callosum, brain stem and cerebellum. These malformations led to severe intellectual disability and early onset seizures or infantile spasms (Brock et al. 2018. PubMed ID: 29706637; Poirier et al. 2013. PubMed ID: 23603762; Di Donato et al. 2018. PubMed ID: 29671837; Romaniello et al. 2017. PubMed ID: 28677066).

For diagnosis of brain malformation, brain imaging techniques such as CT and MRI are the most powerful tools. For example, in the case of tubulinopathies, MRI shows pachygyric cortex with posterior to anterior gradient, enlarged lateral ventricles, variable degrees of reduced white matter volume (Brock et al. 2018. PubMed ID: 29706637; Poirier et al. 2013. PubMed ID: 23603762; Romaniello et al. 2017. PubMed ID: 28677066). In defects of neuronal migration, MRI reveals diffuse periventricular heterotopia, thin corpus callosum, and cortical and hippocampal atrophy (Sheen et al. 2004. PubMed ID: 14647276; Tanyalçin et al. 2013. PubMed ID: 23755938).

Genetics

The genetic etiology of the brain malformation is extremely heterogeneous, ranging from monogenic causes with little or no influence from modifiers or environmental factors to genetically complex forms. In this panel, we mainly focus on a group of genes causative for certain congenital brain malformations. These selected genes have been well documented, such as cortical dysplasia due to defects in structural protein tubulin (TUBA1A, TUBB2A, TUBB2B, TUBB3, TUBB, TUBG1,TUBA8), cortical dysplasia due to defects in actin regulation and neuronal migration (CTNNA2), cortical dysplasia due to defects in microtubule proteins (KIF2A, KIF5C, DYNC1H1), Baraitser-Winter syndrome or lissencephaly due to defect in actin cytoskeleton and microtubule associated proteins (ACTB, ACTG1, DCX), lissencephaly or cerebellar hypoplasia due to defect in Reelin signaling (RELN, VLDLR), cortical malformations or lissencephaly due to defect in epithelial structures laminin or extracellular matrix laminin (LAMC3, LAMB1), heterotopia due to defect in neuronal migration and neurogenesis (ARFGEF2, FLNA, NEDD4L), and heterotopia and lissencephaly due to defects in platelet-activating factor acetylhydrolase (PAFAH1B1). This panel also include genes involving other various cellular functions which cause lissencephaly (ARX, KATNB, MACF1, NDE1, TMTC3), muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies (FKRP, FKTN, LARGE1, POMGNT1, POMT1, POMT2). In total, this panel covers more than 50 disorders (Bahi-Buisson and Cavallin et al. 2016. PubMed ID: 27010057; Spalice et al. 2009. PubMed ID: 19120042; Lange et al. 2015. PubMed ID: 26471271; Parrini et al. 2006. PubMed ID: 16684786; Barak et al. 2011. PubMed ID: 21572413; Bouchet et al. 2007. PubMed ID: 17559086; Di Donato et al. 2018. PubMed ID: 29671837). Brain malformation can be inherited in autosomal dominant, autosomal recessive and X-linked manner. The type of pathogenic variant varies with different genes. For example, the vast majority of pathogenic variants in genes involving tubulinopathies occurr de novo (Bahi-Buisson and Cavallin. 2016. PubMed ID: 27010057; Rodan et al. 2017. PubMed ID: 27770045). Germline mosaicism has been seen in a patient with tubulinopathy (Brock et al. 2018. PubMed ID: 29706637).

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 97.8% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

Brain malformations are clinically and genetically heterogeneous. The sensitivity is variable depending on different disorders. For example, in analysis of FLNA in 120 patients with classical bilateral periventricular nodular heterotopia and periventricular heterotopia, 25 pathogenic variants were detected in 40 patients (Parrini et al. 2006. PubMed ID: 16684786). In a study of the fetal form of type II lissencephaly, 22 out of 41 unrelated families had positive results in genes causative for muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies (Bouchet et al. 2007. PubMed ID: 17559086). When considering lissencephaly, the four most common genes (PAFAH1B1, DCX, TUBA1A, and DYNC1H1) account for 69% of cases (Di Donato et al. 2018. PubMed ID: 29671837).

Indications for Test

The brain malformation panel is recommended for patients suspected to have tubulinopathies, cortical dysplasia, cortical malformations, periventricular heterotopia, lissencephaly, polymicrogyria, pontocerebellar hypoplasia, and muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies.

Diseases

Name Inheritance OMIM ID
Acrocallosal Syndrome, Schinzel Type AR 200990
Al-Gazali-Bakalinova syndrome AR 607131
Baraitser-Winter Syndrome 1 AD 243310
Baraitser-Winter Syndrome 2 AD 614583
Cardiac Valvular Dysplasia, X-Linked XL 314400
Congenital Muscular Dystrophy-Dystroglycanopathy (With Brain And Eye Anomalies) Type A5 AR 613153
Congenital Muscular Dystrophy-Dystroglycanopathy (With Or Without Mental Retardation) Type 5B AR 606612
Cortical Dysplasia, Complex, With Other Brain Malformations AD 614039
Cortical dysplasia, complex, with other brain malformations 2 AD 615282
Cortical dysplasia, complex, with other brain malformations 3 AD 615411
Cortical Dysplasia, Complex, with other Brain Malformations 4 AD 615412
Cortical Dysplasia, Complex, with other Brain Malformations 5 AD 615763
Cortical dysplasia, complex, with other brain malformations 6 AD 615771
Cortical dysplasia, complex, with other brain malformations 9 AR 618174
Cortical Malformations, Occipital AR 614115
Epilepsy, Familial Temporal Lobe, 7 AD 616436
Epileptic encephalopathy, early infantile, 1 XL 308350
FG Syndrome 2 XL 300321
FG Syndrome 4 XL 300422
Frontometaphyseal Dysplasia XL 305620
Fukuyama Congenital Muscular Dystrophy AR 253800
Goldberg-Shprintzen Megacolon Syndrome AR 609460
Heterotopia, Periventricular, Autosomal Recessive AR 608097
Hydrolethalus Syndrome 2 AR 614120
Intestinal Pseudoobstruction Neuronal Chronic Idiopathic X-Linked XL 300048
Lissencephaly 1 AD 607432
Lissencephaly 2 AR 257320
Lissencephaly 3 AD 611603
Lissencephaly 4 AR 614019
Lissencephaly 5 AR 615191
Lissencephaly 6, with microcephaly AR 616212
Lissencephaly 8 AR 617255
Lissencephaly 9 with complex brainstem malformation AD 618325
Martsolf Syndrome AR 212720
Melnick-Needles Syndrome XL 309350
Mental Retardation And Microcephaly With Pontine And Cerebellar Hypoplasia XL 300749
Mental Retardation, Autosomal Dominant 13; MRD13 AD 614563
Mental Retardation, X-Linked, With Or Without Seizures, Arx-Related XL 300419
Microcephaly, short stature, and polymicrogyria with seizures AR 614833
Microhydranencephaly AR 605013
Muscle Eye Brain Disease AR 253280
Muscular Dystrophy-Dystroglycanopathy (Congenital With Brain And Eye Anomalies), Type A, 2 AR 613150
Muscular Dystrophy-Dystroglycanopathy (Congenital With Brain And Eye Anomalies), Type A, 6 AR 613154
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 1 AR 613155
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 2 AR 613156
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 3 AR 613151
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 6 AR 608840
Muscular Dystrophy-Dystroglycanopathy (Congenital Without Mental Retardation), Type B, 4 AR 613152
Oto-Palato-Digital Syndrome Type 1 XL 311300
Oto-Palato-Digital Syndrome, Type II XL 304120
Partington X-Linked Mental Retardation Syndrome XL 309510
Periventricular Nodular Heterotopia 7 AD 617201
Polymicrogyria With Optic Nerve Hypoplasia AR 613180
Polymicrogyria, Asymmetric AD 610031
Polymicrogyria, Bilateral Frontoparietal AR 606854
Polymicrogyria, bilateral perisylvian AR 615752
Pontocerebellar Hypoplasia Type 1 AR 607596
Pontocerebellar Hypoplasia Type 1B AR 614678
Pontocerebellar Hypoplasia Type 2A AR 277470
Pontocerebellar Hypoplasia Type 2B AR 612389
Pontocerebellar Hypoplasia Type 2C AR 612390
Pontocerebellar Hypoplasia Type 4 AR 225753
Pontocerebellar Hypoplasia Type 5 AR 610204
Pontocerebellar Hypoplasia Type 6 AR 611523
Pontocerebellar Hypoplasia Type 8 AR 614961
Primary Autosomal Recessive Microcephaly 2 AR 604317
Proud Levine Carpenter Syndrome XL 300004
Renpenning Syndrome 1 XL 309500
Terminal Osseous Dysplasia XL 300244
VLDLR-Associated Cerebellar Hypoplasia AR 224050
Walker-Warburg Congenital Muscular Dystrophy AR 236670
Warburg Micro Syndrome 1 AR 600118
Warburg Micro Syndrome 2 AR 614225
X-Linked Lissencephaly XL 300067
X-Linked Lissencephaly 2 XL 300215
X-Linked Periventricular Heterotopia XL 300049
X-LinkedMental Retardation With Cerebellar Hypoplasia And Distinctive Facial Appearance XL 300486

Related Test

Name
PGxome®

Citations

  • Bahi-Buisson and Cavallin. 2016. PubMed ID: 27010057
  • Barak et al. 2011. PubMed ID: 21572413
  • Bouchet et al. 2007. PubMed ID: 17559086
  • Brock et al. 2018. PubMed ID: 29706637
  • Di Donato et al. 2018. PubMed ID: 29671837
  • Lange et al. 2015. PubMed ID: 26471271
  • Parrini et al. 2006. PubMed ID: 16684786
  • Poirier et al. 2013. PubMed ID: 23603762
  • Rodan et al. 2017. PubMed ID: 27770045
  • Romaniello et al. 2017. PubMed ID: 28677066
  • Sheen et al. 2004. PubMed ID: 14647276
  • Spalice et al. 2009. PubMed ID: 19120042
  • Tanyalçin et al. 2013. PubMed ID: 23755938

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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