Table 2 Summary of age at diagnosis, details of variants identified and management change in SZ/SZ+ groups.
Group | Age at diagnosis | Gene affected | Gene function | Class | Variant type | Change in management | Outcome at 12 months after change in management |
|---|---|---|---|---|---|---|---|
SZ | 25 days | KCNQ2 | IC | 5 | LoF | Commenced on phenobarbitone | Seizures stopped. Medications weaned off. |
29 days | KCNQ2 | IC | 5 | LoF | Commenced on phenobarbitone | Only 1 minor seizure. Medication weaned off. | |
38 days | SCN2A | IC | 5 | GoF | Changed to carbamazepine | Seizures stopped. Medication weaned off. | |
40 days | SLC6A5 | Dev | 5 | LoF | Clonazepam added. Specialist (neurology) referral | Seizures stopped. Medications weaned off. | |
58 days | SCN8A | IC | 5 | GoF | Changed to sodium channel blocker (lamotrigine) and nitrazepam | Seizures continued (daily multiple seizures). Two attendances to A&E department. | |
102 days | 2q24.3 dup | CNV | 5 | n/a | Changed to carbamazepine | Seizures stopped. Medication weaned off. | |
152 days | SCN2A | IC | 4 | GoF | Changed to carbamazepine | Lost to follow-up | |
392 days | SCN1A | IC | 4 | LoF | Changed to sodium valproate | Seizures continue. At least one admission to PICU required. | |
16 months | POLG | Misc/Mito | 5 | LoF | Ketogenic diet added Avoidance of sodium valproate. Specialist (mitochondrial service) referral | Deceased | |
19 months | SCN1A | IC | 4 | LoF | Changed to sodium valproate | Seizures only at the time of viral illnesses. Continued on medication. | |
SZ+ | 20 days | ASNS | Met | 5 | LoF | Palliative care | Deceased |
23 days | BRAT1 | Dev | 5 | LoF | Palliative care | Deceased | |
29 days | GLDC | Misc/Mito | 5 | LoF | Palliative care | Deceased | |
120 days | CAD | Met | 5 | LoF | Changed to uridine | Seizures stopped. Under the care of a metabolic specialist. | |
172 days | SUOX | Met | 5 | LoF | Palliative care | Deceased | |
272 days | SLC52A3 | Dev | 4 | LoF | Changed to riboflavin | Seizures stopped. One PICU admission and long-term inpatient care required. | |
1 year | ALG13 | Met | 5 | LoF | Ketogenic diet added | Seizures increased in frequency: absence seizures most days and myoclonic jerks up to 2-3 times a day. Three attendances to A&E department. | |
2 years | KCTD7 | IC | 5 | LoF | Specialist (metabolic medicine) referral | Seizures stopped. Continued only on medication for dystonia. One attendance to A&E department. | |
2.4 years | ABCD5 | Met | 5 | LoF | Specialist (metabolic medicine) referral | Seizures increased. Required several attendances to A&E department. | |
4.5 years | TPP1 | Met | 5 | LoF | Commenced on ceroliponase, specialist (metabolic medicine) referral | Seizures continued but at reduced frequency (50%). Successfully weaned off topiramide and clobazam. | |
7 years | KCNQ5 | IC | 4 | GoF | Changed to carbamazepine, ketogenic diet added | Seizures continued. A couple of Tonic-clonic seizures a day. Clobazam added. Attended A&E department 4 times. | |
13.5 years | 3q28q29 del 3q28dup, 10qdup | CNV | 5 | n/a | Changed to phenytoin | Lost to follow-up |
