Table 3.
Patient phenotypes.
| ID | Sex | Gene | Age | Epilepsy phenotype | ID | Family Hx epilepsy | Seizure onset | Seizure types | Cognitive and behavioural features | Associated features | EEG | EEG abnormalities | MRI |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | DYNC1H1 | Adult | Focal epilepsy | Y | N | 13–18 months | GAS, GTCS | ID, BI | Did not achieve usual milestones, no regression noted, awkward gait | Abnormal | Multifocal epileptiform | Abnormal (frontal cortical dysplasia) |
| 5 | F | ALDH5A1 | Adult | Generalised epilepsy | Y | Y | 6 years | GTCS | Moderate ID, Mood disorder, BI | Hypothyroidism, chronic constipation | Abnormal | Focal slowing | NA |
| 9 | M | CHD2 | Adult | Generalised epilepsy | Y | N | Unknown | GTCS, GTAS | ID and ASD | Slow to meet milestones, speech delay | Abnormal | Generalied epileptiform | NA |
| 25 | F | DCX | Adult | Generalised epilepsy | Y | N | <6 months | GTCS, CPS | Severe ID, BI, Self-injurous behaviour | Non-verbal, regression | Abnormal | Generalied epileptiform | Abnormal (bilateral pachygyria) |
| 30 | M | CHD2 | Adult | Focal epilepsy | Y | N | 4 years | GTCS, GTS | ID and ASD | Met early milestones, lack of skills progression age 4, started losing acquired skills age 6 | NA | NA | NA |
| 34 | M | PURA | Adult | Generalised epilepsy | Y | N | 16 years | GTCS | Moderate-Severe ID | Hypotonia, missed all milestones | Abnormal | Both generalised and focal epileptiform | Normal |
| 37 | M | MBD5 | Adult | Febrile and drop seizures | Y | Y | 9 months | FS, TCS, DS | Mild ID and ASD | Milestones slightly delayed | NA | NA | NA |
| 39 | M | MBD5 | Adult | Febrile and drop seizures | Y | Y | Unknown | GTCS | Moderate ID | Non-verbal, poor social skills | Normal | Normal | Normal |
| 42 | M | SCN1A | Paed | Generalised epilepsy | Y | N | <6 months | CPS, FS, GTAS | Mild ID, Global development delay | Grade 2 ureteric reflux (significant family history of renal disease) | Normal and Abnormal | Normal | Normal |
| 43 | F | STXBP1 | Paed | Generalised epilepsy | Y | N | <6 months | GTCS, GTS | Severe ID | ACTH induced cardiomyopathy and myopathy, Kyphosis thoracic spine, Scoliosis lumbar spine, hip dysplasia, myopic astigmatism | Abnormal | Epileptic encephalopathy | Abnormal (atrophy) |
| 50 | F | GABRA1 | Adult | Generalised epilepsy | Y | N | 2 years | GMS, GTCS, GAAS | Severe ID, ASD, BI | Delayed Milestones | Normal | Normal | Normal |
| 52 | F | SMC1A | Adult | Generalised epilepsy | Y | N | Unknown | GTCS, GMS | Moderate ID | Selective mutism | NA | NA | Normal |
| 55 | M | TSC1 | Adult | Generalised epilepsy | Y | N | 6–12 months | GTCS, GTAS | Severe ID, BI, Self-injurous behaviour | Ventral Septal Defect, Chronic ear dermatitis and otitis media, Strep Viridans Endocarditis, Chronic Renal Failure, IGa Nephropathy, Hypertension, Ungal Fibromas | NA | NA | NA |
| 57 | M | FGFR3 | Adult | Generalised epilepsy | Y | Y | <6 months | GTAS, GTCS | Severe ID and ASD | Challenging behaviour | NA | NA | NA |
| 75 | M | FGFR3 | Adult | Single, unprovoked event | Y | Y | <6 months | Severe ID | Delayed development, head circumference on 75th centile. Coarse features | Abnormal | Multifocal epileptiform | NA | |
| 58 | M | STXBP1 | Paed | Generalised epilepsy | Y | N | <6 months | GTCS | Global Developmental Delay | Dysmorphic features, left side weakness, weak neck, metabolic workup normal | Abnormal | Focal epileptiform | Normal (reduction in white matter noted) |
| 59 | F | CNV (ATP2A1,TUFM) | Paed | Generalised epilepsy | Y | N | Unknown | GAS, CPS, GMS, GTCS | ID, ASD, Pica | Non-verbal, over-weight, regression | Abnormal | Both generalised and focal epileptiform | Normal |
| 61 | M | NONO | Adult | Unclassified epilepsy syndrome | Y | N | Unknown | Head shaking and staring | Severe ID | Incontinent | Abnormal | Generalised slowing | NA |
| 68 | M | ALG13 | Paed | Generalised epilepsy, West syndrome. | Y | N | 6–12 months | GTS, GCS, GTAS | Severe ID | Missed all milestones, not able to indicate needs | Abnormal | Multifocal epileptiform | NA |
| 71 | F | CHD2 | Paed | Idiopathic generalised epilepsy | Y | N | 3 years | GTS, GMS | Mild-moderate ID | Regression from age 3, Myocoloic astatic phenotype | Abnormal | Both generalised and focal epileptiform | Normal |
| 73 | M | NEDD4L | Paed | Generalised epilepsy | Y | N | 2 years | GAS, GTCS, GAAS, GTS, GMS | Global Developmental Delay | Hypotonia, poor coordination, strabismus right eye | Abnormal | Generalied epileptiform | NA |
| 83 | M | PAFAH1B1 | Adult | Generalised epilepsy | Y | N | 2 years | GTCS, CPS | Severe ID | Delayed milestones, non-verbal | Abnormal | Generalied epileptiform | Abnormal (lissencephaly) |
| 84 | M | CNV (RORA) | Paed | Focal epilepsy | Y | N | 4 years | GTAS, CPS | Global Developmental Delay | Myopia, adaptive behavourial and cognitive intellectual disability, dysmorphic features | Abnormal | Multifocal epileptiform | Normal |
| 88 | M | PPP3CA | Paed | Paediatric epilepsy syndrome | Y | N | 2 years | GTCS, GMS, GCS | Language delay, autistic features | Possible ataxia, met early milestones | Abnormal | Generalised slowing | Normal |
| 89 | F | GRIN2A | Adult | Paediatric epilepsy syndrome | Y | N | 4 years | CPS | Speech and language delay, BI, normal development until 4 years and then regressed | Early puberty (10 years of age), tall stature | Abnormal | Multifocal epileptiform | Normal (small, ovoid fatty mass to the left of the midbrain) |
| 96 | F | SCN1A | Adult | Generalised epilepsy | Y | N | 6–12 months | GTCS, GTAS | Moderate-Severe ID | History of febrile seizures | Abnormal | Generalied epileptiform | NA |
| 97 | F | ANKRD11 | Adult | Generalised epilepsy | Y | Y | 12 years | GTCS, GTAS | Mild ID, attends main-stream scholing | Slow to meet milestones | Abnormal | Generalied epileptiform | Normal |
| 98 | F | ANKRD11 | Adult | Generalised epilepsy | Y | Y | 11 years | GTCS, GAAS | Mild ID | Slow to meet milestones, had twin to twin transfusion syndrome | Abnormal | Generalied epileptiform | Normal |
| 100 | M | KPTN | Adult | Generalised epilepsy | Y | Y | 4 years | GTCS | Moderate-Severe ID | Behavioural problems, contractures, dysphagia | Abnormal | Focal slowing | NA |
| 101 | M | CACNA1A | Adult | Focal/Generalised epilepsy | Y | N | 6 years | GMS, GTCS, GTAS, GTS | Mild ID/ Learning difficulties | Oseopenia, behavioural problems | Abnormal | Generalied epileptiform | Normal |
| 108 | F | SYNGAP1 | Paed | Focal/Generalised epilepsy | Y | N | 6 years | GAS | Profound ID, global developmental delay, ASD | Did not meet milestones, non-verbal, microcephalic, poor circulation, hypotonic | Abnormal | Both generalised and focal epileptiform | Normal |
| 109 | F | SCN1A | Adult | Generalised epilepsy | Y | N | 13–18 months | GTCS, GMS | Moderate ID | Early development normal, regression from age 9/10 | Abnormal | Multifocal epileptiform | Undetermined (no acute intracranial abnormality) |
| 111 | M | PTEN | Adult | Generalised epilepsy | Y | N | 9 years | GTCS, GMS, GTS | Mild ID | Macrocephaly, regression from 10 years of age, cough variant asthma and eczema | Abnormal | Both generalised and focal epileptiform | Normal |
| Potential incidental findings: | |||||||||||||
| 6 | M | KCNH2 | Adult | Idiopathic generalised epilepsy | Y | N | 6 years | GTS, GMS, GTCS, GTAS | ID | Abnormal development noted at age 6 | Abnormal | Generalied epileptiform | Normal |
| 65 | F | KCNQ1 | Adult | Generalised epilepsy | Y | N | 3 months | GTCS, GMS | Severe ID | NA | NA | NA | |
| 96 | F | MYH11 | Adult | Generalised epilepsy | Y | N | 6–12 months | GTCS, GTAS | Moderate-Severe ID | History of febrile seizures | Abnormal | Generalied epileptiform | NA |
| 108 | F | VHL | Paed | Focal/Generalised epilepsy | Y | N | 6 years | GAS | Profound ID, global developmental delay, ASD | Did not meet milestones, non-verbal, microcephalic, poor circulation, hypotonic | Abnormal | Both generalised and focal epileptiform | Normal |
| Less secure (not ACMG confirmed), noteworthy variants: | |||||||||||||
| 29 | F | LRP2 | Adult | Generalised epilepsy | Y | N | 14 years | GCS, GTCS | Severe ID | Microcephaly, bilateral hearing loss, abnormality of cerebellum | NA | NA | NA |
| 36 | M | OPHN1 | Adult | Generalised epilepsy | Y | N | 3 years | GTCS, GTAS | Mild ID | Heart murmer as a child, hypothyroidism, ataxic gait | NA | NA | Abnormal (microcephalic, arachnoid cyst) |
GTCS generalised tonic clonic seizures, ID intellectual disability, NA not available, FHx family history, GTAS generalised typical absence seizures, CPS complex partial seizures, BI behavioural issues, ASD austism spectrum disorder, GTS generalised tonic seizures, FS febrile seizures, TCS tonic clonic seizures, DS drop seizures, GTAS generalised typical absence seizures, GMS generalised myoclonic seizures, GAAS generalised atypical absence seizures, GCS generalised clonic seizures, SPS simple partial seizures, GAS generalised atonic seizures.