Table 1.

Clinical features of patients with Developmental and Epileptic Encephalopathy and recurrent KCNC1 missense variant p.Ala421Val.

Patient	1	2	3	4	5	6
Inheritance	De novo	De novo	De novo	De novo	De novo	De novo
Gender	F	M	F	M	F	M
Age at onset	Birth	3 months	10 months	9 months	9.5 months	5 months
Seizure types	Myoclonic Atypical absence GTCS	Focal to bilateral tonic clonic Focal	GTCS Focal Myoclonic	Myoclonic Atypical absence Atonic GTCS	Myoclonic	Myoclonic GTCS Absence with myoclonus Focal to bilateral tonic clonic
Response to treatment	Refractory	Response to LMT and VPA	Refractory then response to VPA Clobazam Stiripentol	Refractory to medication, response to VNS	Response to LEV and LMT	Response to VPA
Age at walking	2.5 years	3 years	2.5 years	2 years	2.5 years	3 years
Intelligible speech	Yes	Yes	Yes	Yes	Yes	Yes
Cognitive Function	Severe ID	Moderate‐severe ID	Moderate‐severe ID	Moderate‐severe ID	Global developmental delayb	Moderate ID
Neurological Features	Ataxiaa	Ataxiaa, severe hypotonia	Nil	Ataxiaa, mild decreased power, hypotonia	Ataxiaa, mild athetosis, hypotonia	Unsteady gait, hypotonia
Co‐morbidities	Behavioural disturbance	EsophagitisSleeping disturbance Failure to thrive Pectus excavatum	Nil	GERD, Chronic diarrhoea, Failure to thrive, Central sleep apnoea, Autism Functional B cell deficiency	Nil	Sleep disturbance Hypermobile joints Stereotypies
Clinical course	Refractory seizures age 16	Monthly seizures at 3 years	Seizure control improved age 15	<1 seizure every 3 months post VNS	Seizures every 2–3 months	Seizure control improved at age 9

Abbreviations: GERD, gastro‐esophageal reflux disease; ID, intellectual disability; GTCS, generalized tonic clonic seizures; LEV, levetiracetam; LMT, lamotrigine; VNS, vagal nerve stimulator; VPA, sodium valproate.

^aAtaxia, where noted, was mild and non‐progressive.

^bChild too young for grading of intellectual disability.