Comprehensive Epilepsy Panel, Sequencing and Deletion/Duplication

Last Literature 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 (i.e., 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 ClassAnalytic Sensitivity (PPA) Estimatea (%) and 95% Credibility RegionAnalytic Specificity (NPA) Estimate (%)
SNVs>99 (96.9-99.4)>99.9
Deletions 1-10 bpb93.8 (84.3-98.2)>99.9
Insertions 1-10 bpb94.8 (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 duplications83.3 (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 DisordersInheritance
AARS1 (601065)Developmental and epileptic encephalopathy 29AR
Hereditary diffuse leukoencephalopathy with spheroids 2AD
ABAT (137150)GABA-transaminase deficiencyAR
ADGRG1 (604110)Bilateral frontoparietal polymicrogyria; bilateral perisylvian polymicrogyriaAR
ADSL (608222)Adenylosuccinase deficiencyAR
ALDH5A1 (610045)Succinic semialdehyde dehydrogenase deficiencyAR
ALDH7A1 (107323)Pyridoxine-dependent epilepsyAR
ALG1 (605907)Congenital disorder of glycosylation type IkAR
ALG13 (300776)Developmental and epileptic encephalopathy 36XL
ALG3 (608750)Congenital disorder of glycosylation type IdAR
ALG6 (604566)Congenital disorder of glycosylation type IcAR
ALG8 (608103)Congenital disorder of glycosylation type IhAR
ALG9 (606941)Congenital disorder of glycosylation type Il; Gillessen-Kaesbach-Nishimura syndromeAR
AMACR (604489)Alpha-methylacyl-CoA racemase deficiencyAR
AMT (238310)Glycine encephalopathyAR
ANKRD11 (611192)KBG syndromeAD
AP3B2 (602166)Developmental and epileptic encephalopathy 48AR
ARFGEF2 (605371)Periventricular heterotopia with microcephalyAR
ARG1 (608313)ArgininemiaAR
ARHGEF9 (300429)Developmental and epileptic encephalopathy 8XL
ARV1 (611647)Developmental and epileptic encephalopathy 38AR
ARX (300382Developmental and epileptic encephalopathy 1; Proud syndrome; XL lissencephaly 2 with ambiguous genitalia; XL intellectual developmental disorder 29XL
ASAH1 (613468)Spinal muscular atrophy with progressive myoclonic epilepsyAR
ASNS (108370)Asparagine synthetase deficiencyAR
ATN1 (607462)Congenital hypotonia, epilepsy, developmental delay, and digital anomaliesAD
ATP1A1 (182310)Hypomagnesemia, seizures, and impaired intellectual development 2AD
ATP1A3 (182350)Alternating hemiplegia of childhood 2; developmental and epileptic encephalopathy 99AD
ATP6AP2 (300556)Syndromic intellectual developmental disorder Hedera typeXL
ATP7A (300011)Menkes diseaseXL
ATRX (300032)Alpha-thalassemia/mental retardation syndrome; XL intellectual disability-hypotonic facies syndromeXL
BCKDK (614901)Branched-chain keto acid dehydrogenase kinase deficiencyAR
BRAT1 (614506)Neurodevelopmental disorder with cerebellar atrophy and with or without seizures; rigidity and multifocal seizure syndrome, lethal neonatalAR
BTD (609019)Biotinidase deficiencyAR
C12orf57 (615140)Temtamy syndromeAR
CACNA1A (601011)Developmental and epileptic encephalopathy 42; episodic ataxia type 2; familial hemiplegic migraine 1AD
CACNA1D (114206)Primary aldosteronism, seizures, and neurologic abnormalitiesAD
CACNA1E (601013)Developmental and epileptic encephalopathy 69AD
CACNA2D2 (607082)Cerebellar atrophy with seizures and variable developmental delayAR
CAD (114010)Developmental and epileptic encephalopathy 50AR
CARS2 (612800)Combined oxidative phosphorylation deficiency 27AR
CASK (300172)FG syndrome 4; intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasiaXL
CDKL5 (300203)Developmental and epileptic encephalopathy 2XL
CHD2 (602119)Developmental and epileptic encephalopathy 94AD
CHRNA4 (118504)Nocturnal frontal lobe epilepsy 1AD
CHRNB2 (118507)Nocturnal frontal lobe epilepsy 3AD
CLCN4 (302910)Raynaud-Claes syndromeXL
CLN3 (607042)Neuronal ceroid lipofuscinosis 3AR
CLN5 (608102)Neuronal ceroid lipofuscinosis 5AR
CLN6 (606725)Neuronal ceroid lipofuscinosis types 6A and 6B (Kufs type)AR
CLN8 (607837)Neuronal ceroid lipofuscinosis 8; northern epilepsy variantAR
CLTC (118955)Intellectual developmental disorder 56AD
CNKSR2 (300724)XL syndromic intellectual developmental disorder (Houge type)XL
CNTNAP2 (604569)Pitt-Hopkins like syndrome 1AR
COL4A1 (120130)Brain small vessel disease with or without ocular anomaliesAD
CPT2 (600650)CPT II deficiency (infantile or neonatal lethal)AR
Susceptibility to acute infection-induced encephalopathy 4AD/AR
CSTB (601145)Progressive myoclonic epilepsy 1A (Unverricht and Lundborg)AR
CTSD (116840)Neuronal ceroid lipofuscinosis 10AR
CTSF (603539)Neuronal ceroid lipofuscinosis13 (Kufs type)AR
CUL4B (300304)XL syndromic intellectual developmental disorder, Cabezas typeXL
DCX (300121)XL lissencephaly or subcortical laminal heterotopiaXL
DDX3X (300160)XL syndromic intellectual developmental disorder, Snijders Blok typeXL
DEAF1 (602635)Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizuresAR
Vulto-van Silfout-de Vries syndromeAD
DEPDC5 (614191)Familial focal epilepsy with variable foci 1AD
DHDDS (608172)Developmental delay and seizures with or without movement abnormalitiesAD
Congenital disorder of glycosylation type 1bb/retinitis pigmentosa 59AR
DIAPH1 (602121)Seizures, cortical blindness, microcephaly syndromeAR
DMXL2 (612186)Developmental and epileptic encephalopathy 81AR
DNAJC5 (611203)Neuronal ceroid lipofuscinosis 4 (Kufs type)AD
DNM1 (602377)Developmental and epileptic encephalopathy 31AD
DNM1L (603850)Lethal encephalopathy due to defective mitochondrial peroxisomal fission 1AR/AD
DOCK7 (615730)Developmental and epileptic encephalopathy 23AR
DPAGT1 (191350)Congenital disorder of glycosylation type IjAR
DPM1 (603503)Congenital disorder of glycosylation type IeAR
DPYD (612779)Dihydropyrimidine dehydrogenase deficiencyAR
DYNC1H1 (600112)Complex cortical dysplasia with other brain malformationsAD
DYRK1A (600855)Intellectual developmental disorder 7AD
EEF1A2 (602959)Developmental and epileptic encephalopathy 33; intellectual developmental disorder 38AD
EHMT1 (607001)Kleefstra syndrome 1AD
EPM2A (607566)Progressive myoclonic epilepsy 2A (Lafora)AR
FARS2 (611592)Combined oxidative phosphorylation deficiency 14AR
FGF12 (601513)Developmental and epileptic encephalopathy 47AD
FKTN (607440)Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A4AR
FLNA (300017)Neuronal intestinal pseudoobstruction; periventricular heterotopia 1XL
FOLR1 (136430)Neurodegeneration due to cerebral folate transport deficiencyAR
FOXG1 (164874)Congenital variant Rett syndromeAD
FRRS1L (604574)Developmental and epileptic encephalopathy 37AR
GABBR2 (607340)Developmental and epileptic encephalopathy 59; neurodevelopmental disorder with poor language and loss of hand skillsAD
GABRA1 (137160)Developmental and epileptic encephalopathy 19; susceptibility to childhood absence or juvenile myoclonic epilepsyAD
GABRB2 (600232)Developmental and epileptic encephalopathy 92AD
GABRB3 (137192)Developmental and epileptic encephalopathy 43; susceptibility to childhood absence epilepsyAD
GABRD (137163)Idiopathic generalized epilepsy 10; susceptibility to juvenile myoclonic epilepsy; susceptibility to generalized epilepsy with febrile seizures type 5AD
GABRG2 (137164)Developmental and epileptic encephalopathy 74; familial febrile seizures 8; generalized epilepsy with febrile seizures plus type 3AD
GALC (606890)Krabbe diseaseAR
GAMT (601240)Cerebral creatine deficiency syndrome 2AR
GATM (602360)Cerebral creatine deficiency syndrome 3AR
GFAP (137780)Alexander diseaseAD
GNAO1 (139311)Developmental and epileptic encephalopathy 17; neurodevelopmental disorder with involuntary movementsAD
GNB1 (139380)Intellectual developmental disorder 42AD
GOSR2 (604027)Congenital muscular dystrophy with or without seizures; progressive myoclonic epilepsy 6AR
GPHN (603930)Molybdenum cofactor deficiency CAR
GRIA3 (305915)XL syndromic intellectual developmental disorder (Wu type)XL
GRIN1 (138249)Developmental and epileptic encephalopathy 101AR
Neurodevelopmental disorder with or without hyperkinetic movements and seizuresAR/AD
GRIN2A (138253)Epilepsy, focal, with speech disorder and with or without impaired intellectual developmentAD
GRIN2B (138252)Developmental and epileptic encephalopathy 27; intellectual developmental disorder 6 with or without seizuresAD
HACE1 (610876)Spastic paraplegia and psychomotor retardation with or without seizuresAR
HCN1 (602780)Developmental and epileptic encephalopathy 24; generalized epilepsy with febrile seizures plus type 10AD
HECW2 (617245)Neurodevelopmental disorder with hypotonia, seizures, and absent languageAD
HNRNPU (602869)Developmental and epileptic encephalopathy 54AD
HSD17B10 (300256)HSD10 mitochondrial diseaseXL
IQSEC2 (300522)XL intellectual developmental disorder 1XL
ITPA (147520)Developmental and epileptic encephalopathy 35AR
KANSL1 (612452)Koolen-De Vries syndromeAD
KCNA1 (176260)Episodic ataxia/myokymia syndromeAD
KCNA2 (176262)Developmental and epileptic encephalopathy 32AD
KCNB1 (600397)Developmental and epileptic encephalopathy 26AD
KCNC1 (176258)Progressive myoclonic epilepsy 7AD
KCNH1 (603305)Temple-Baraitser syndrome; Zimmermann-Laband syndrome 1AD
KCNJ10 (602208)SESAME syndromeAR
KCNJ11 (600937)Permanent neonatal diabetes 2 with or without neurologic featuresAD
KCNMA1 (600150)Cerebellar atrophy, developmental delay, and seizuresAR
Liang-Wang syndrome paroxysmal nonkinesigenic dyskinesia 3 with or without generalized epilepsy; susceptibility to idiopathic generalized epilepsy 16AD
KCNQ2 (602235)Benign neonatal seizures 1; developmental and epileptic encephalopathy 7AD
KCNQ3 (602232)Benign neonatal seizures 2AD
KCNT1 (608167)Developmental and epileptic encephalopathy 14; nocturnal frontal lobe epilepsy 5AD
KCTD7 (611725)Progressive myoclonic epilepsy 3 with or without intracellular inclusionsAR
KDM5C (314690)XL syndromic intellectual developmental disorder (Claes-Jensen type)XL
KIF1A (601255)NESCAV syndromeAD
LGI1 (604619)Familial temporal lobe epilepsy 1AD
MBD5 (611472)Intellectual developmental disorder 1AD
MDH2 (154100)Developmental and epileptic encephalopathy 51AR
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 atrophyAR
MEF2C (600662)Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired languageAD
MFSD8 (611124)Neuronal ceroid lipofuscinosis 7AR
MOCS2 (603708)Molybdenum cofactor deficiency BAR
MOGS (601336)Congenital disorder of glycosylation type IIbAR
MPDU1 (604041)Congenital disorder of glycosylation type IfAR
MTHFR (607093)Homocystinuria due to MTHFR deficiencyAR
MTOR (601231)Smith-Kingsmore syndromeAD
NDE1 (609449)Lissencephaly 4 with microcephalyAR
NECAP1 (611623)Developmental and epileptic encephalopathy 21AR
NEDD4L (606384)Periventricular nodular heterotopia 7AD
NEU1 (608272)Sialidosis type I or IIAR
NEXMIF (300524)XL intellectual developmental disorder 98XL
NGLY1 (610661)Congenital disorder of deglycosylation 1AR
NHLRC1 (608072)Progressive myoclonic epilepsy 2B (Lafora)AR
NPRL2 (607072)Familial focal epilepsy with variable foci 2AD
NPRL3 (600928)Familial focal epilepsy with variable foci 3AD
NR2F1 (132890)Bosch-Boonstra-Schaaf optic atrophy syndromeAD
NRXN1 (600565)Pitt-Hopkins-like syndrome 2AR
NSD1 (606681)Sotos syndromeAD
NTRK2 (600456)Developmental and epileptic encephalopathy 58; obesity, hyperphagia, and developmental delayAD
OPHN1 (300127)XL syndromic intellectual developmental disorder (Billuart type)XL
PACS1 (607492)Schuurs-Hoeijmakers syndromeAD
PAFAH1B1 (601545)Lissencephaly 1AD
PCDH19 (300460)Developmental and epileptic encephalopathy 9XL
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 10BAR
PEX6 (601498)Peroxisome biogenesis disorder 4A (Zellweger) or 4BAR
PHF6 (300414)Borjeson-Forssman-Lehmann syndromeXL
PHGDH (606879)Phosphoglycerate dehydrogenase deficiencyAR
PIGA (311770)Multiple congenital anomalies-hypotonia-seizures syndrome 2; neurodevelopmental disorder with epilepsy and hemochromatosisXL
PIGG (616918)Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophyAR
PIGN (606097)Multiple congenital anomalies-hypotonia-seizures syndrome 1AR
PIGO (614730)Hyperphosphatasia with impaired intellectual development syndrome 2AR
PIGQ (605754)Multiple congenital anomalies-hypotonia-seizures syndrome 4AR
PIGT (610272)Multiple congenital anomalies-hypotonia-seizures syndrome 3AR
PIGV (610274)Hyperphosphatasia with impaired intellectual development syndrome 1AR
PLCB1 (607120)Developmental and epileptic encephalopathy 12AR
PLPBP (604436)Early-onset vitamin B6-dependent epilepsyAR
PMM2 (601785)Congenital disorder of glycosylation type IaAR
PNKP (605610)Microcephaly, seizures, and developmental delayAR
PNPO (603287)Pyridoxamine 5'-phosphate oxidase deficiencyAR
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 1AR
PRICKLE2 (608501)Early-onset epilepsyAD
PRRT2 (614386)Benign familial infantile seizures 2; episodic kinesigenic dyskinesia 1; familial infantile convulsions with paroxysmal choreoathetosisAD
PSAP (176801)Atypical Gaucher disease; atypical Krabbe disease; combined SAP deficiency; metachromatic leukodystrophy due to SAP-b deficiencyAR
PTPN23 (606584)Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticityAR
PURA (600473)Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficultiesAD
QARS1 (603727)Microcephaly, progressive, seizures, and cerebral and cerebellar atrophyAR
QDPR (612676)Hyperphenylalaninemia BH4-deficient CAR
RELN (600514)Familial temporal lobe epilepsy 7AD
Lissencephaly 2 (Norman-Roberts type)AR
RFT1 (611908)Congenital disorder of glycosylation type InAR
RNASEH2A (606034)Aicardi-Goutieres syndrome 4AR
RNASEH2B (610326)Aicardi-Goutieres syndrome 2AR
RNASEH2C (610330)Aicardi-Goutieres syndrome 3AR
ROGDI (614574)Kohlschutter-Tonz syndromeAR
RORB (601972)Susceptibility to idiopathic generalized epilepsy 15AD
SAMHD1 (606754)Aicardi-Goutieres syndrome 5AR
SATB2 (608148)Glass syndromeAD
SCARB2 (602257)Progressive myoclonic epilepsy 4 with or without renal failureAR
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 2AD
SCN1B (600235)Developmental and epileptic encephalopathy 52AR
Generalized epilepsy with febrile seizures plus type 1AD
SCN2A (182390)Benign familial infantile seizures 3; developmental and epileptic encephalopathy 11; episodic ataxia type 9AD
SCN3A (182391)Developmental and epileptic encephalopathy 62; familial focal epilepsy with variable foci 4AD
SCN8A (600702)Benign familial infantile seizures 5; developmental and epileptic encephalopathy 13AD
SERPINI1 (602445)Familial encephalopathy with neuroserpin inclusion bodiesAD
SETBP1 (611060)Intellectual developmental disorder 29; Schinzel-Giedion midface retraction syndromeAD
SLC12A5 (606726)Developmental and epileptic encephalopathy 34AR
Susceptibility to idiopathic generalized epilepsy 14AD
SLC13A5 (608305)Developmental and epileptic encephalopathy 25, with amelogenesis imperfectaAR
SLC19A3 (606152)Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2)AR
SLC1A2 (600300)Developmental and epileptic encephalopathy 41AD
SLC25A12 (603667)Developmental and epileptic encephalopathy 39AR
SLC25A22 (609302)Developmental and epileptic encephalopathy 3AR
SLC2A1 (138140)GLUT1 deficiency syndrome 1 infantile onsetAD/AR
Dystonia 9; GLUT1 deficiency syndrome 2, childhood onset: stomatin-deficient cryohydrocytosis with neurologic defects; susceptibility to idiopathic generalized epilepsy 12AD
SLC35A2 (314375)Congenital disorder of glycosylation type IImXL
SLC6A1 (137165)Myoclonic-atonic epilepsyAD
SLC9A6 (300231)XL syndromic intellectual developmental disorder (Christianson type)XL
SMARCA2 (600014)Blepharophimosis-impaired intellectual development syndrome; Nicolaides-Baraitser syndromeAD
SMC1A (300040)Cornelia de Lange syndrome 2; developmental and epileptic encephalopathy 85 with or without midline brain defectsXL
SMS (300105)XL syndromic intellectual developmental disorder (Snyder-Robinson type)XL
SNAP25 (600322)Congenital myasthenic syndrome 18AD
SPATA5 (613940)Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalitiesAR
SPTAN1 (182810)Developmental and epileptic encephalopathy 5AD
ST3GAL3 (606494)Developmental and epileptic encephalopathy 15AR
ST3GAL5 (604402)Salt and pepper developmental regression syndromeAR
STRADA (608626)Polyhydramnios, megalencephaly, and symptomatic epilepsyAR
STX1B (601485)Generalized epilepsy with febrile seizures plus type 9AD
STXBP1 (602926)Developmental and epileptic encephalopathy 4AD/AR
SUOX (606887)Sulfite oxidase deficiencyAR
SYN1 (313440)XL epilepsy 1 with variable learning disabilities and behavior disordersXL
SYNGAP1 (603384)Intellectual developmental disorder 5AD
SYNJ1 (604297)Early-onset Parkinson disease 20; developmental and epileptic encephalopathy 53AR
SZT2 (615463)Developmental and epileptic encephalopathy 18AR
TBC1D24 (613577)Developmental and epileptic encephalopathy 16; DOORS syndrome; familial infantile myoclonic epilepsy; rolandic epilepsy with paroxysmal exercise-induce dystonia and writer's crampAR
TBL1XR1 (608628)Intellectual developmental disorder 41; Pierpont syndromeAD
TCF4 (602272)Pitt-Hopkins syndromeAD
TPK1 (606370)Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type)AR
TPP1 (607998)Neuronal ceroid lipofuscinosis 2AR
TREX1 (606609)Aicardi-Goutieres syndrome 1AR/AD
Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestationsAD
TSC1 (605284)Tuberous sclerosis-1AD
TSC2 (191092)Tuberous sclerosis-2AD
TSEN54 (608755)Pontocerebellar hypoplasia (types 2A, 4, 5)AR
UBA5 (610552)Developmental and epileptic encephalopathy 44AR
UBE3A (601623)Angelman syndromeAD
UNC80 (612636)Infantile hypotonia with psychomotor retardation and characteristic facies 2AR
VPS13A (605978)ChoreoacanthocytosisAR
WDR45 (300526)Neurodegeneration with brain iron accumulation 5XL
WWOX (605131)Developmental and epileptic encephalopathy 28; spinocerebellar ataxia, 12AR
ZEB2 (605802)Mowat-Wilson syndromeAD
AD, autosomal dominant; AR, autosomal recessive; XL, X-linked

References