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

4, class 4 likely pathogenic variant; 5, class 5 pathogenic variant.

CNV copy number variants, del deletion, Dev developmental genes, dup duplication, GoF gain-of-function variant, IC ion channel, LoF loss-of-function variant, Met metabolic genes, Misc/Mito miscellaneous/mitochondrial genes (both nuclear and mitochondrial genes).