Comprehensive Epilepsy Panel, Sequencing and Deletion/Duplication

Content Review: August 2023 Last Update:

Recommended test to establish a diagnosis or determine the genetic etiology of an epilepsy or seizure disorder

If a familial sequence variant has been previously identified, targeted sequencing for that variant may be appropriate; refer to the Laboratory Test Directory for additional information.

Epilepsy is a neurological disorder that causes recurrent unprovoked seizures and affects approximately 1% of the population.  It can be subclassified by seizure type (ie, focal, generalized, generalized and focal, or unknown) and can take idiopathic or syndromic forms. An estimated 30% of epilepsy cases are believed to have a genetic contribution,  and there is high genetic heterogeneity and significant phenotypic overlap between conditions. In addition to clinical evaluation and nonlaboratory testing, genetic testing can be useful to identify the basis of a patient’s epilepsy and to inform prognosis, optimal treatment and management, recurrence risk, and testing of at-risk relatives. 

Disease Overview

According to guidelines from the National Society of Genetic Counselors, patients with unexplained epilepsy, regardless of age of onset, should be offered genetic testing. 

Both focal and generalized epilepsy can have a genetic cause. Factors that increase the likelihood of a genetic cause include  :

  • Earlier age of seizure onset
  • Presence of neurodevelopmental comorbidities such as intellectual disability, developmental delay, autism spectrum disorder, and/or encephalopathy
  • Drug-resistant epilepsy
  • A family history of epilepsy

Genetics

Genes

This panel includes genes associated with Mendelian forms of idiopathic epilepsy and syndromic epilepsy in which seizures are a major or presenting feature.

Refer to Genes Tested for additional details.

Etiology

Epilepsy may have infectious, structural, genetic, metabolic, immune, or unknown causes. An estimated 30% of epilepsy has a genetic cause.  Pathogenic germline variants in numerous genes have been associated with epilepsy. 

Inheritance

Epilepsy may occur sporadically or as a familial trait with autosomal dominant, autosomal recessive, or X-linked inheritance. De novo variation is a common cause of sporadic epileptic encephalopathy.

Penetrance

Variable; influenced by gene and variant.

Test Interpretation

Methodology

This test is performed using the following sequence of steps:

  • Selected genomic regions, primarily coding exons and exon-intron boundaries, from the targeted genes are isolated from extracted genomic DNA using a probe-based hybrid capture enrichment workflow.
  • Enriched DNA is sequenced by massively parallel sequencing (MPS; also known as next generation sequencing, or NGS), followed by paired-end read alignment and variant calling using a custom bioinformatics pipeline. The pipeline includes an algorithm for detection of large deletions and duplications.
  • Sanger sequencing is performed as necessary to fill in regions of low coverage and, in certain situations, to confirm variant calls.
  • Large deletion/duplication calls made using MPS are confirmed by an orthogonal exon-level microarray when sample quality and technical conditions allow.

Clinical Sensitivity

Dependent on clinical phenotype.

Analytic Sensitivity/Specificity

Variant Class Analytic Sensitivity (PPA) Estimatea (%) and 95% Credibility Region Analytic Specificity (NPA) Estimate (%)

SNVs

>99 (96.9-99.4)

>99.9

Deletions 1-10 bpb

93.8 (84.3-98.2)

>99.9

Insertions 1-10 bpb

94.8 (86.8-98.5)

>99.9

Exon-levelc deletions

97.8 (90.3-99.8) [2 exons or larger]

62.5 (38.3-82.6) [Single exon]

>99.9

Exon-levelc duplications

83.3 (56.4-96.4) [3 exons or larger]

>99.9

aPPA values are derived from larger methods-based MPS and/or Sanger validations. These values do not apply to testing performed by multiplex ligation-dependent probe amplification (MLPA) unless otherwise indicated.

bVariants greater than 10 bp may be detected, but the analytic sensitivity may be reduced.

cIn most cases, a single exon deletion or duplication is less than 450 bp and 3 exons span a genomic region larger than 700 bp.

bp, base pairs; NPA, negative percent agreement; PPA, positive percent agreement; SNVs, single nucleotide variants

Limitations

  • A negative result does not exclude a heritable form of epilepsy.
  • Diagnostic errors can occur due to rare sequence variations.
  • Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.
  • The following will not be evaluated:
    • Variants outside the coding regions and intron-exon boundaries of the targeted gene(s)
    • Variants in the mitochondrial genome
    • Regulatory region and deep intronic variants
    • Deletions/duplications in the DYNC1H1, EMP2A, FARS2, SLC19A3, and WWOX genes
    • Breakpoints of large deletions/duplications
    • Gene conversion events, complex inversions, and translocations
    • Repeat expansions (including common expansions in ATN1 exon 5, ARX, and CSTB 5’UTR)
    • This assay does not assess for PMM2-associated hyperinsulinemic hypoglycemia and polycystic kidney disease (HIPKD)
    • SNVs and small deletions/insertions will not be called in the following exons due to technical limitations of the assay:
      • ABAT (NM_001386615) 6
      • ABAT (NM_001386616) partial exon 16(Chr16:8875107-8875145)
      • ADSL (NM_001363840) 14
      • ALG13 (NM_001099922, NM_001257231) partial exon 24(ChrX:110987954-110988035)
      • ALG9 (NM_001352420, NM_001352421) 15
      • ALG9 (NM_001352415, NM_001352416, NM_001352419) 16
      • ALG9 (NM_001352417) 17
      • ANKRD11 (NM_013275, NM_001256183) partial exon 9(Chr16:89345816-89346020)
      • ANKRD11 (NM_001256182) partial exon 10(Chr16:89345816-89346020)
      • ANKRD11 (NM_013275, NM_001256183) 13
      • ANKRD11 (NM_001256182) 14
      • AP3B2 (NM_001348440) 5
      • ARHGEF9 (NM_001353923) 1
      • ARV1 (NM_001346992) 4
      • ARX (NM_139058) partial exon 2(ChrX:25031469-25031834)
      • BRAT1 (NM_001350626) partial exon 14(Chr7:2578419-2578578)
      • BTD (NM_001370752) 5
      • BTD (NM_001370753) 4
      • CARS2 (NM_001352253) 9
      • CLN5 (NM_001366624) 4
      • CUL4B (NM_001369145) 1
      • DMXL2 (NM_001378459) 32
      • DMXL2 (NM_001378463) partial exon 32(Chr15:51755500-51755555)
      • DMXL2 (NM_001378457, NM_001378458) 34
      • DNM1 (NM_001374269) 22
      • EHMT1 (NM_024757, NM_001145527, NM_001354263, NM_001354611) 1
      • EHMT1 (NM_001354259) 16
      • EHMT1 (NM_001354612) partial exon 9(Chr9:140657293-140657296)
      • EHMT1 (NM_001354611) partial exon 10(Chr9:140657293-140657296)
      • EPM2A (NM_001368129, NM_001368132) 3
      • EPM2A (NM_001368130) partial exon 3(Chr6:145956295-145956360)
      • FKTN (NM_001351497) 6
      • FKTN (NM_001351498) partial exon 9(Chr9:108382363-108382373)
      • FOXG1 (NM_005249) partial exon 1(Chr14:29236682-29236856)
      • GABBR2 (NM_005458, NM_001375347) 1
      • GABRG2 (NM_001375344) 7
      • GPHN (NM_001377519, NM_001377514) 5
      • GPHN (NM_001377515, NM_001377516, NM_001377517, NM_001377518) 9
      • GPHN (NM_001377514, NM_001377515, NM_001377516) 10
      • GPHN (NM_001377514) 11
      • KCNQ2 (NM_001382235) 15
      • KCTD7 (NM_001167961) 5
      • KDM5C (NM_001353979, NM_001353981, NM_001353982, NM_001353984) 26
      • KIF1A (NM_001379636) 36
      • KIF1A (NM_001379639) 37
      • KIF1A (NM_001379635, NM_001379638, NM_001379646) 38
      • MBD5 (NM_001378120) partial exon 9(Chr2:149241026-149241704)
      • NR2F1 (NM_005654) partial exon 1(Chr5:92920778-92920891)
      • NTRK2 (NM_001369547) 13
      • PLPBP (NM_001349349) partial exon 1(Chr8:37620073-37620157)
      • PLPBP (NM_001349349) 5
      • PLPBP (NM_001349346) partial exon 6(Chr8:37632827-37632836)
      • RORB (NM_001365023) 1
      • SAMHD1 (NM_001363733) 16
      • SLC19A3 (NM_001371413, NM_001371414) 3
      • SLC9A6 (NM_001379110) 14
      • SMARCA2 (NM_003070, NM_001289396, NM_001289397, NM_139045) 5
      • SPTAN1 (NM_001375318, NM_001375312) 2
      • SPTAN1 (NM_001375310) 50
      • SPTAN1 (NM_001363759) 52
      • SPTAN1 (NM_001375318) 53
      • ST3GAL3 (NM_001350619, NM_001350620) 12
      • ST3GAL3 (NM_001350621) 6,13
      • STXBP1 (NM_001374313, NM_001374314) 19
      • SYNGAP1 (NM_006772) partial exon 19(Chr6:33419581-33419683)
      • SZT2 (NM_001365999) 22
      • TPK1 (NM_001350884) 3
      • TPK1 (NM_001350883) 4
      • TPK1 (NM_001350882) 5
      • TPK1 (NM_001350895) 7
      • TPK1 (NM_001350881) 9
      • TSEN54 (NM_207346) 1
      • UBE3A (NM_001354523) 5
      • UNC80 (NM_001371986) 27
  • The following may not be detected:
    • Deletions/duplications/insertions of any size by MPS
    • Large duplications less than 3 exons in size
    • Noncoding transcripts
    • Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions
    • Low-level somatic or mosaic variants

Genes Tested

Gene Symbol (OMIM Number) Associated Disorders Inheritance

AARS1 (601065)

Developmental and epileptic encephalopathy 29

AR

Hereditary diffuse leukoencephalopathy with spheroids 2

AD

ABAT (137150)

GABA-transaminase deficiency

AR

ADGRG1 (604110)

Bilateral frontoparietal polymicrogyria; bilateral perisylvian polymicrogyria

AR

ADSL (608222)

Adenylosuccinase deficiency

AR

ALDH5A1 (610045)

Succinic semialdehyde dehydrogenase deficiency

AR

ALDH7A1 (107323)

Pyridoxine-dependent epilepsy

AR

ALG1 (605907)

Congenital disorder of glycosylation type Ik

AR

ALG13 (300776)

Developmental and epileptic encephalopathy 36

XL

ALG3 (608750)

Congenital disorder of glycosylation type Id

AR

ALG6 (604566)

Congenital disorder of glycosylation type Ic

AR

ALG8 (608103)

Congenital disorder of glycosylation type Ih

AR

ALG9 (606941)

Congenital disorder of glycosylation type Il; Gillessen-Kaesbach-Nishimura syndrome

AR

AMACR (604489)

Alpha-methylacyl-CoA racemase deficiency

AR

AMT (238310)

Glycine encephalopathy

AR

ANKRD11 (611192)

KBG syndrome

AD

AP3B2 (602166)

Developmental and epileptic encephalopathy 48

AR

ARFGEF2 (605371)

Periventricular heterotopia with microcephaly

AR

ARG1 (608313)

Argininemia

AR

ARHGEF9 (300429)

Developmental and epileptic encephalopathy 8

XL

ARV1 (611647)

Developmental and epileptic encephalopathy 38

AR

ARX (300382

Developmental and epileptic encephalopathy 1; Proud syndrome; XL lissencephaly 2 with ambiguous genitalia; XL intellectual developmental disorder 29

XL

ASAH1 (613468)

Spinal muscular atrophy with progressive myoclonic epilepsy

AR

ASNS (108370)

Asparagine synthetase deficiency

AR

ATN1 (607462)

Congenital hypotonia, epilepsy, developmental delay, and digital anomalies

AD

ATP1A1 (182310)

Hypomagnesemia, seizures, and impaired intellectual development 2

AD

ATP1A3 (182350)

Alternating hemiplegia of childhood 2; developmental and epileptic encephalopathy 99

AD

ATP6AP2 (300556)

Syndromic intellectual developmental disorder Hedera type

XL

ATP7A (300011)

Menkes disease

XL

ATRX (300032)

Alpha-thalassemia/mental retardation syndrome; XL intellectual disability-hypotonic facies syndrome

XL

BCKDK (614901)

Branched-chain keto acid dehydrogenase kinase deficiency

AR

BRAT1 (614506)

Neurodevelopmental disorder with cerebellar atrophy and with or without seizures; rigidity and multifocal seizure syndrome, lethal neonatal

AR

BTD (609019)

Biotinidase deficiency

AR

C12orf57 (615140)

Temtamy syndrome

AR

CACNA1A (601011)

Developmental and epileptic encephalopathy 42; episodic ataxia type 2; familial hemiplegic migraine 1

AD

CACNA1D (114206)

Primary aldosteronism, seizures, and neurologic abnormalities

AD

CACNA1E (601013)

Developmental and epileptic encephalopathy 69

AD

CACNA2D2 (607082)

Cerebellar atrophy with seizures and variable developmental delay

AR

CAD (114010)

Developmental and epileptic encephalopathy 50

AR

CARS2 (612800)

Combined oxidative phosphorylation deficiency 27

AR

CASK (300172)

FG syndrome 4; intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia

XL

CDKL5 (300203)

Developmental and epileptic encephalopathy 2

XL

CHD2 (602119)

Developmental and epileptic encephalopathy 94

AD

CHRNA4 (118504)

Nocturnal frontal lobe epilepsy 1

AD

CHRNB2 (118507)

Nocturnal frontal lobe epilepsy 3

AD

CLCN4 (302910)

Raynaud-Claes syndrome

XL

CLN3 (607042)

Neuronal ceroid lipofuscinosis 3

AR

CLN5 (608102)

Neuronal ceroid lipofuscinosis 5

AR

CLN6 (606725)

Neuronal ceroid lipofuscinosis types 6A and 6B (Kufs type)

AR

CLN8 (607837)

Neuronal ceroid lipofuscinosis 8; northern epilepsy variant

AR

CLTC (118955)

Intellectual developmental disorder 56

AD

CNKSR2 (300724)

XL syndromic intellectual developmental disorder (Houge type)

XL

CNTNAP2 (604569)

Pitt-Hopkins like syndrome 1

AR

COL4A1 (120130)

Brain small vessel disease with or without ocular anomalies

AD

CPT2 (600650)

CPT II deficiency (infantile or neonatal lethal)

AR

Susceptibility to acute infection-induced encephalopathy 4

AD/AR

CSTB (601145)

Progressive myoclonic epilepsy 1A (Unverricht and Lundborg)

AR

CTSD (116840)

Neuronal ceroid lipofuscinosis 10

AR

CTSF (603539)

Neuronal ceroid lipofuscinosis13 (Kufs type)

AR

CUL4B (300304)

XL syndromic intellectual developmental disorder, Cabezas type

XL

DCX (300121)

XL lissencephaly or subcortical laminal heterotopia

XL

DDX3X (300160)

XL syndromic intellectual developmental disorder, Snijders Blok type

XL

DEAF1 (602635)

Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures

AR

Vulto-van Silfout-de Vries syndrome

AD

DEPDC5 (614191)

Familial focal epilepsy with variable foci 1

AD

DHDDS (608172)

Developmental delay and seizures with or without movement abnormalities

AD

Congenital disorder of glycosylation type 1bb/retinitis pigmentosa 59

AR

DIAPH1 (602121)

Seizures, cortical blindness, microcephaly syndrome

AR

DMXL2 (612186)

Developmental and epileptic encephalopathy 81

AR

DNAJC5 (611203)

Neuronal ceroid lipofuscinosis 4 (Kufs type)

AD

DNM1 (602377)

Developmental and epileptic encephalopathy 31

AD

DNM1L (603850)

Lethal encephalopathy due to defective mitochondrial peroxisomal fission 1

AR/AD

DOCK7 (615730)

Developmental and epileptic encephalopathy 23

AR

DPAGT1 (191350)

Congenital disorder of glycosylation type Ij

AR

DPM1 (603503)

Congenital disorder of glycosylation type Ie

AR

DPYD (612779)

Dihydropyrimidine dehydrogenase deficiency

AR

DYNC1H1 (600112)

Complex cortical dysplasia with other brain malformations

AD

DYRK1A (600855)

Intellectual developmental disorder 7

AD

EEF1A2 (602959)

Developmental and epileptic encephalopathy 33; intellectual developmental disorder 38

AD

EHMT1 (607001)

Kleefstra syndrome 1

AD

EPM2A (607566)

Progressive myoclonic epilepsy 2A (Lafora)

AR

FARS2 (611592)

Combined oxidative phosphorylation deficiency 14

AR

FGF12 (601513)

Developmental and epileptic encephalopathy 47

AD

FKTN (607440)

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A4

AR

FLNA (300017)

Neuronal intestinal pseudoobstruction; periventricular heterotopia 1

XL

FOLR1 (136430)

Neurodegeneration due to cerebral folate transport deficiency

AR

FOXG1 (164874)

Congenital variant Rett syndrome

AD

FRRS1L (604574)

Developmental and epileptic encephalopathy 37

AR

GABBR2 (607340)

Developmental and epileptic encephalopathy 59; neurodevelopmental disorder with poor language and loss of hand skills

AD

GABRA1 (137160)

Developmental and epileptic encephalopathy 19; susceptibility to childhood absence or juvenile myoclonic epilepsy

AD

GABRB2 (600232)

Developmental and epileptic encephalopathy 92

AD

GABRB3 (137192)

Developmental and epileptic encephalopathy 43; susceptibility to childhood absence epilepsy

AD

GABRD (137163)

Idiopathic generalized epilepsy 10; susceptibility to juvenile myoclonic epilepsy; susceptibility to generalized epilepsy with febrile seizures type 5

AD

GABRG2 (137164)

Developmental and epileptic encephalopathy 74; familial febrile seizures 8; generalized epilepsy with febrile seizures plus type 3

AD

GALC (606890)

Krabbe disease

AR

GAMT (601240)

Cerebral creatine deficiency syndrome 2

AR

GATM (602360)

Cerebral creatine deficiency syndrome 3

AR

GFAP (137780)

Alexander disease

AD

GNAO1 (139311)

Developmental and epileptic encephalopathy 17; neurodevelopmental disorder with involuntary movements

AD

GNB1 (139380)

Intellectual developmental disorder 42

AD

GOSR2 (604027)

Congenital muscular dystrophy with or without seizures; progressive myoclonic epilepsy 6

AR

GPHN (603930)

Molybdenum cofactor deficiency C

AR

GRIA3 (305915)

XL syndromic intellectual developmental disorder (Wu type)

XL

GRIN1 (138249)

Developmental and epileptic encephalopathy 101

AR

Neurodevelopmental disorder with or without hyperkinetic movements and seizures

AR/AD

GRIN2A (138253)

Epilepsy, focal, with speech disorder and with or without impaired intellectual development

AD

GRIN2B (138252)

Developmental and epileptic encephalopathy 27; intellectual developmental disorder 6 with or without seizures

AD

HACE1 (610876)

Spastic paraplegia and psychomotor retardation with or without seizures

AR

HCN1 (602780)

Developmental and epileptic encephalopathy 24; generalized epilepsy with febrile seizures plus type 10

AD

HECW2 (617245)

Neurodevelopmental disorder with hypotonia, seizures, and absent language

AD

HNRNPU (602869)

Developmental and epileptic encephalopathy 54

AD

HSD17B10 (300256)

HSD10 mitochondrial disease

XL

IQSEC2 (300522)

XL intellectual developmental disorder 1

XL

ITPA (147520)

Developmental and epileptic encephalopathy 35

AR

KANSL1 (612452)

Koolen-De Vries syndrome

AD

KCNA1 (176260)

Episodic ataxia/myokymia syndrome

AD

KCNA2 (176262)

Developmental and epileptic encephalopathy 32

AD

KCNB1 (600397)

Developmental and epileptic encephalopathy 26

AD

KCNC1 (176258)

Progressive myoclonic epilepsy 7

AD

KCNH1 (603305)

Temple-Baraitser syndrome; Zimmermann-Laband syndrome 1

AD

KCNJ10 (602208)

SESAME syndrome

AR

KCNJ11 (600937)

Permanent neonatal diabetes 2 with or without neurologic features

AD

KCNMA1 (600150)

Cerebellar atrophy, developmental delay, and seizures

AR

Liang-Wang syndrome paroxysmal nonkinesigenic dyskinesia 3 with or without generalized epilepsy; susceptibility to idiopathic generalized epilepsy 16

AD

KCNQ2 (602235)

Benign neonatal seizures 1; developmental and epileptic encephalopathy 7

AD

KCNQ3 (602232)

Benign neonatal seizures 2

AD

KCNT1 (608167)

Developmental and epileptic encephalopathy 14; nocturnal frontal lobe epilepsy 5

AD

KCTD7 (611725)

Progressive myoclonic epilepsy 3 with or without intracellular inclusions

AR

KDM5C (314690)

XL syndromic intellectual developmental disorder (Claes-Jensen type)

XL

KIF1A (601255)

NESCAV syndrome

AD

LGI1 (604619)

Familial temporal lobe epilepsy 1

AD

MBD5 (611472)

Intellectual developmental disorder 1

AD

MDH2 (154100)

Developmental and epileptic encephalopathy 51

AR

MECP2 (300005)

Rett syndrome; severe neonatal encephalopathy; XL autism susceptibility 3; XL syndromic intellectual developmental disorder (Lubs type or 13)

XL

MED17 (603810)

Postnatal progressive microcephaly with seizures and brain atrophy

AR

MEF2C (600662)

Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

AD

MFSD8 (611124)

Neuronal ceroid lipofuscinosis 7

AR

MOCS2 (603708)

Molybdenum cofactor deficiency B

AR

MOGS (601336)

Congenital disorder of glycosylation type IIb

AR

MPDU1 (604041)

Congenital disorder of glycosylation type If

AR

MTHFR (607093)

Homocystinuria due to MTHFR deficiency

AR

MTOR (601231)

Smith-Kingsmore syndrome

AD

NDE1 (609449)

Lissencephaly 4 with microcephaly

AR

NECAP1 (611623)

Developmental and epileptic encephalopathy 21

AR

NEDD4L (606384)

Periventricular nodular heterotopia 7

AD

NEU1 (608272)

Sialidosis type I or II

AR

NEXMIF (300524)

XL intellectual developmental disorder 98

XL

NGLY1 (610661)

Congenital disorder of deglycosylation 1

AR

NHLRC1 (608072)

Progressive myoclonic epilepsy 2B (Lafora)

AR

NPRL2 (607072)

Familial focal epilepsy with variable foci 2

AD

NPRL3 (600928)

Familial focal epilepsy with variable foci 3

AD

NR2F1 (132890)

Bosch-Boonstra-Schaaf optic atrophy syndrome

AD

NRXN1 (600565)

Pitt-Hopkins-like syndrome 2

AR

NSD1 (606681)

Sotos syndrome

AD

NTRK2 (600456)

Developmental and epileptic encephalopathy 58; obesity, hyperphagia, and developmental delay

AD

OPHN1 (300127)

XL syndromic intellectual developmental disorder (Billuart type)

XL

PACS1 (607492)

Schuurs-Hoeijmakers syndrome

AD

PAFAH1B1 (601545)

Lissencephaly 1

AD

PCDH19 (300460)

Developmental and epileptic encephalopathy 9

XL

PEX1 (602136)

Peroxisome biogenesis disorder 1A (Zellweger) or 1B (NALD/IRD)

AR

PEX12 (601758)

Peroxisome biogenesis disorder 3A (Zellweger)

AR

PEX2 (170993)

Peroxisome biogenesis disorder 5A (Zellweger)

AR

PEX3 (603164)

Peroxisome biogenesis disorder 10A (Zellweger) or 10B

AR

PEX6 (601498)

Peroxisome biogenesis disorder 4A (Zellweger) or 4B

AR

PHF6 (300414)

Borjeson-Forssman-Lehmann syndrome

XL

PHGDH (606879)

Phosphoglycerate dehydrogenase deficiency

AR

PIGA (311770)

Multiple congenital anomalies-hypotonia-seizures syndrome 2; neurodevelopmental disorder with epilepsy and hemochromatosis

XL

PIGG (616918)

Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy

AR

PIGN (606097)

Multiple congenital anomalies-hypotonia-seizures syndrome 1

AR

PIGO (614730)

Hyperphosphatasia with impaired intellectual development syndrome 2

AR

PIGQ (605754)

Multiple congenital anomalies-hypotonia-seizures syndrome 4

AR

PIGT (610272)

Multiple congenital anomalies-hypotonia-seizures syndrome 3

AR

PIGV (610274)

Hyperphosphatasia with impaired intellectual development syndrome 1

AR

PLCB1 (607120)

Developmental and epileptic encephalopathy 12

AR

PLPBP (604436)

Early-onset vitamin B6-dependent epilepsy

AR

PMM2 (601785)

Congenital disorder of glycosylation type Ia

AR

PNKP (605610)

Microcephaly, seizures, and developmental delay

AR

PNPO (603287)

Pyridoxamine 5'-phosphate oxidase deficiency

AR

POLG (174763)

Mitochondrial DNA depletion syndrome type 4A (Alpers type) or 4B (MNGIE type); mitochondrial recessive ataxia syndrome (includes SANDO and SCAE)

AR

PPT1 (600722)

Neuronal ceroid lipofuscinosis 1

AR

PRICKLE2 (608501)

Early-onset epilepsy

AD

PRRT2 (614386)

Benign familial infantile seizures 2; episodic kinesigenic dyskinesia 1; familial infantile convulsions with paroxysmal choreoathetosis

AD

PSAP (176801)

Atypical Gaucher disease; atypical Krabbe disease; combined SAP deficiency; metachromatic leukodystrophy due to SAP-b deficiency

AR

PTPN23 (606584)

Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity

AR

PURA (600473)

Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties

AD

QARS1 (603727)

Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy

AR

QDPR (612676)

Hyperphenylalaninemia BH4-deficient C

AR

RELN (600514)

Familial temporal lobe epilepsy 7

AD

Lissencephaly 2 (Norman-Roberts type)

AR

RFT1 (611908)

Congenital disorder of glycosylation type In

AR

RNASEH2A (606034)

Aicardi-Goutieres syndrome 4

AR

RNASEH2B (610326)

Aicardi-Goutieres syndrome 2

AR

RNASEH2C (610330)

Aicardi-Goutieres syndrome 3

AR

ROGDI (614574)

Kohlschutter-Tonz syndrome

AR

RORB (601972)

Susceptibility to idiopathic generalized epilepsy 15

AD

SAMHD1 (606754)

Aicardi-Goutieres syndrome 5

AR

SATB2 (608148)

Glass syndrome

AD

SCARB2 (602257)

Progressive myoclonic epilepsy 4 with or without renal failure

AR

SCN1A (182389)

Dravet syndrome; developmental and epileptic encephalopathy 6B (non-Dravet); familial febrile seizures 3A; familial hemiplegic migraine 3; generalized epilepsy with febrile seizures plus type 2

AD

SCN1B (600235)

Developmental and epileptic encephalopathy 52

AR

Generalized epilepsy with febrile seizures plus type 1

AD

SCN2A (182390)

Benign familial infantile seizures 3; developmental and epileptic encephalopathy 11; episodic ataxia type 9

AD

SCN3A (182391)

Developmental and epileptic encephalopathy 62; familial focal epilepsy with variable foci 4

AD

SCN8A (600702)

Benign familial infantile seizures 5; developmental and epileptic encephalopathy 13

AD

SERPINI1 (602445)

Familial encephalopathy with neuroserpin inclusion bodies

AD

SETBP1 (611060)

Intellectual developmental disorder 29; Schinzel-Giedion midface retraction syndrome

AD

SLC12A5 (606726)

Developmental and epileptic encephalopathy 34

AR

Susceptibility to idiopathic generalized epilepsy 14

AD

SLC13A5 (608305)

Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta

AR

SLC19A3 (606152)

Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2)

AR

SLC1A2 (600300)

Developmental and epileptic encephalopathy 41

AD

SLC25A12 (603667)

Developmental and epileptic encephalopathy 39

AR

SLC25A22 (609302)

Developmental and epileptic encephalopathy 3

AR

SLC2A1 (138140)

GLUT1 deficiency syndrome 1 infantile onset

AD/AR

Dystonia 9; GLUT1 deficiency syndrome 2, childhood onset: stomatin-deficient cryohydrocytosis with neurologic defects; susceptibility to idiopathic generalized epilepsy 12

AD

SLC35A2 (314375)

Congenital disorder of glycosylation type IIm

XL

SLC6A1 (137165)

Myoclonic-atonic epilepsy

AD

SLC9A6 (300231)

XL syndromic intellectual developmental disorder (Christianson type)

XL

SMARCA2 (600014)

Blepharophimosis-impaired intellectual development syndrome; Nicolaides-Baraitser syndrome

AD

SMC1A (300040)

Cornelia de Lange syndrome 2; developmental and epileptic encephalopathy 85 with or without midline brain defects

XL

SMS (300105)

XL syndromic intellectual developmental disorder (Snyder-Robinson type)

XL

SNAP25 (600322)

Congenital myasthenic syndrome 18

AD

SPATA5 (613940)

Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities

AR

SPTAN1 (182810)

Developmental and epileptic encephalopathy 5

AD

ST3GAL3 (606494)

Developmental and epileptic encephalopathy 15

AR

ST3GAL5 (604402)

Salt and pepper developmental regression syndrome

AR

STRADA (608626)

Polyhydramnios, megalencephaly, and symptomatic epilepsy

AR

STX1B (601485)

Generalized epilepsy with febrile seizures plus type 9

AD

STXBP1 (602926)

Developmental and epileptic encephalopathy 4

AD/AR

SUOX (606887)

Sulfite oxidase deficiency

AR

SYN1 (313440)

XL epilepsy 1 with variable learning disabilities and behavior disorders

XL

SYNGAP1 (603384)

Intellectual developmental disorder 5

AD

SYNJ1 (604297)

Early-onset Parkinson disease 20; developmental and epileptic encephalopathy 53

AR

SZT2 (615463)

Developmental and epileptic encephalopathy 18

AR

TBC1D24 (613577)

Developmental and epileptic encephalopathy 16; DOORS syndrome; familial infantile myoclonic epilepsy; rolandic epilepsy with paroxysmal exercise-induce dystonia and writer's cramp

AR

TBL1XR1 (608628)

Intellectual developmental disorder 41; Pierpont syndrome

AD

TCF4 (602272)

Pitt-Hopkins syndrome

AD

TPK1 (606370)

Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type)

AR

TPP1 (607998)

Neuronal ceroid lipofuscinosis 2

AR

TREX1 (606609)

Aicardi-Goutieres syndrome 1

AR/AD

Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations

AD

TSC1 (605284)

Tuberous sclerosis-1

AD

TSC2 (191092)

Tuberous sclerosis-2

AD

TSEN54 (608755)

Pontocerebellar hypoplasia (types 2A, 4, 5)

AR

UBA5 (610552)

Developmental and epileptic encephalopathy 44

AR

UBE3A (601623)

Angelman syndrome

AD

UNC80 (612636)

Infantile hypotonia with psychomotor retardation and characteristic facies 2

AR

VPS13A (605978)

Choreoacanthocytosis

AR

WDR45 (300526)

Neurodegeneration with brain iron accumulation 5

XL

WWOX (605131)

Developmental and epileptic encephalopathy 28; spinocerebellar ataxia, 12

AR

ZEB2 (605802)

Mowat-Wilson syndrome

AD

AD, autosomal dominant; AR, autosomal recessive; XL, X-linked

References