Table 3.
Summary of the clinical findings from the eight most common single-gene epilepsies
| Genetic cause | ||||
|---|---|---|---|---|
| PRRT2 | SCN1A | KCNQ2 | SLC2A1 | |
| Number of patients in this cohort and whether related | 17 (8 female) | 14 (5 female) | 10 (5 female) | 7 (3 female) |
| All unrelated | All unrelated | All unrelated | All unrelated | |
| Incidence | 1 per 9970 live births | 1 per 12 200 live births | 1 per 17 000 live births | 1 per 24,300 live births |
| (10.0/100 000; 95% CI 5.26–14.8). | (8.26/100 000; 95% CI 3.93–12.6). | (5.89/100 000; 95% CI 2.24–9.56). | (4.13/100 000; 95% CI 1.07–7.19). | |
| Age range at presentation in months (median) | 3–19 (7) | 1.5–19 (6.5) | 0.17–4 (0.24) | 11–18 (12) |
| Most common presentation(s) | Afebrile focal seizures: 71% (12/17) | Febrile seizures: 50% (7/14) | Afebrile focal seizures: 70% (7/10) | Afebrile generalized seizures: 86% (6/7) |
| Afebrile focal seizures: 36% (5/14) | ||||
| Status epilepticus: 36% (5/14) | ||||
| Diagnosis at latest follow-up | Self-limited infantile epilepsy: 88% (15/17) | Dravet syndrome: 79% (11/14) | Self-limited neonatal epilepsy: 60% (6/10) | Glut1-deficiency with epilepsy: 100% (7/7) |
| Unclassified focal epilepsy: 6% (1/17) | Febrile seizures only: 14% (2/14) | KCNQ2 encephalopathy: 20% (2/10) | ||
| Unclassified epilepsy: 6% (1/17) | Genetic epilepsy with febrile seizures plus: 7% (1/14) | Self-limited infantile epilepsy: 10% (1/10) | ||
| Unclassified focal epilepsy: 10% (1/10) | ||||
| Developmental concerns at presentation | 24% (4/17) | 29% (4/14) (29%) | 20% (2/10) | 57% (4/7) |
| Developmental concerns at follow-up | 12% (2/17) | 64% (9/14) | 30% (3/10) | 43% (3/7) |
| Therapy-resistant seizures | None (0/17) | 86% (12/14) | 20% (2/10) | 14% (1/7) |
| Recommended treatment(s) (Table 4) | Carbamazepine | Stiripentol | Carbamazepine | Ketogenic diet |
| Fenfluramine | Phenytoin | |||
| Cannabidiol | ||||
| Avoidance of sodium channel blocking medications | ||||
| Zygosity | 100% heterozygous (17/17) | 100% heterozygous (14/14) | 100% heterozygous (10/10) | 100% heterozygous (7/7) |
| Inheritance of causative variant | 12% de novo (2/17) | 70% de novo (10/14) | 30% de novo (3/10) | 70% de novo (5/7) |
| 71% inherited (12/17) | 30% inherited (3/14) | 50% inherited (5/10) | 15% inherited (1/7) | |
| 18% unknown (3/17) | 10% unknown (1/14) | 20% unknown (2/10) | 15% unknown (1/7) | |
| Genetic cause | ||||
| CDKL5 | PCDH19 | DEPDC5 | SLC6A1 | |
| Number of patients in this cohort and whether related | 4 (3 female) | 4 (all female) | 4 (2 female) | 4 (all female) |
| All unrelated | All unrelated | All unrelated | 3 were siblings | |
| Incidence | 1 per 42 400 live births | 1 per 20 600 live born females | 1 per 42 400 live births | N/A |
| 2.36/100 000 (95% CI 0.805–5.59) | 4.85/100 000 (95% CI 1.97–9.15) | 2.36/100 000 (95% CI 0.81–5.59) | ||
| Age range at presentation in months (median) | 0.5–6 (1.65) | 6–18 (11.5) | 2.5–26 (20) | 12–31 (19) |
| Most common presentation(s) | Infantile spasms: 50% (2/4) | Afebrile focal seizures: 75% (3/4) | Afebrile focal seizures: 50% (2/4) | Afebrile focal seizures: 75% (3/4) |
| Afebrile focal seizures: 50% (2/4) | ||||
| Diagnosis at latest follow-up | CDKL5 developmental and epileptic encephalopathy: 100% (4/4) | PCDH19 related developmental and epileptic encephalopathy: 75% (3/4) | Unclassified focal epilepsy: 75% (3/4) | Unclassified epilepsy 75% (3/4) |
| Unclassified epilepsy: 25% (1/4) | Infantile spasms (West syndrome) 25% (1/4) | Epilepsy with myoclonic-atonic seizures 25% (1/4) | ||
| Developmental concerns at presentation | 50% (2/4) | None (0/4) | None (0/4) | 75% (3/4) |
| Developmental concerns at follow-up | 100% (4/4) | 75% (3/4) | 25% (1/4) | 100% (4/4) |
| Therapy-resistant seizures | 100% (4/4) | 100% (4/4) | 50% (2/4) | 50% (2/4) |
| Recommended treatment(s) (Table 4) | Ketogenic diet | Clobazam | No specific recommendation | Sodium valproate |
| Zygosity | 75% heterozygous (3/4) | 100% heterozygous (4/4) | 100% heterozygous (4/4) | 100% heterozygous (4/4) |
| 25% hemizygous (1/4) | ||||
| Inheritance of causative variant | 75% de novo (3/4) | 50% paternally inherited (2/4) | 50% de novo (2/4) | 100% inherited (4/4) |
| 25% unknown (1/4) | 50% de novo (2/4) | 50% inherited (2/4) | ||