Table 5.

Summary of the Clinical Features of Individuals with DNMs in DHDDS (GenBank: NM_024887.3) and NUS1 (GenBank: NM_138459.4)

ID	Gender	Age at Last Examination	Gene	DNM (Detection)	Cognitive and Behavioral Features	Epilepsy Diagnosis	Age at Seizure Onset	Seizure Types	AEDs	EEG	Brain MRI	Associated Neurological Features and Seizure Outcome
indvSG	female	5 years, 1 month	DHDDS	c.110G>A (p.Arg37His) (cWESa)	GDD, severe ID	DEE	18 months	MA photo+, GTC, febrile Fo	VPA, LTG, LEV, ETH, VPA	gen. SW, photo+	normal	hypotonia, short stature, intractable seizures
HSJ0762	male	5 years, 6 months	DHDDS	c.110G>A (p.Arg37His) (WGSb)	GDD	DEE	1 years	M, A, At, fever sensitive	LEV, VPA	gen. SW, diffuse slowing	normal	hypotonia, tremor, wide-based gate, ataxia, no seizures for 1 year on VPA
indvEF	female	5 years, 6 months	DHDDS	c.632G>A (p.Arg211Gln) (cWESc)	GDD, borderline IQ	DEE	4 years	MA	LEV, LTG, OXBZ	epileptiform	normal, Chiari I malformation	hypotonia, tremor, ataxia, inattention, obesity, seizures controlled with OXBZ
MDB31882	male	35 years	DHDDS	c.632G>A (p.Arg211Gln) (WESd)	GDD, severe ID	DEE	6–9 years	M	VPA, benzodiazepines	gen. PSW	normal	gen. tremor, facial myokimia, bradykinesia, hypomimia, rigidity, freezing and impaired postural reactions, frontal lobe impairment features, no seizures since the age of 9 years, normal glycosylation assay, current therapy: VPA, clonazepam, tetrabenazine
indvNCJ	female	7 years, 1 month	DHDDS	c.632G>A (p.Arg211Gln) (cWESe)	GDD, moderate to severe ID	NA	7 years	M	none	normal	normal	ataxia, myoclonus, tremor, dystonia, short stature, no treatment initiated yet for cortical myoclonus, normal glycosylation assay
indvKW	male	7 years, 11 months	NUS1	c.743delA (p.Asp248Alafs) (cWESc)	GDD, severe ID	DEE	12 months	M, GTC	LEV	biF epileptiform	normal	ataxia with LEV, lack of coordination, seizures controlled with LEV
HSJ0623	male	15 years	NUS1	c.128_141dup (p.Val48Profs)∗7 (WGSb)	GDD, moderate ID, ASD	DEE	10 months	MA, At, febrile GTC	VPA, LTG, LEV, ETH, CZP, CBZ, Stiri., CLB	diffuse slowing, biF or gen spikes	normal	ADHD, tremor, seizures controlled under VPA and CLB
HSJ0627	female	20 years	NUS1	exon 2 deletion (WGSb)	motor delay, mild ID	DEE	2.5 years	M status, MA, At	VPA, LEV, CLB, FEL, LTG, CZP	gen. SW and PSW	normal	tremor, dysarthria, seizures controlled on VPA, LTG, and CZP

Underlining indicates treatment with clinical response (decreased seizure frequency or severity), and italics indicates a negative response (aggravation of seizure frequency and/or severity). Abbreviations are as follows: NA, not applicable; cWES, clinical whole-exome sequencing; WGS, whole-genome sequencing; GDD, global developmental delay; ID, intellectual disability; IQ, intelligence quotient; ASD, autism spectrum disorder; DEE, developmental and epileptic encephalopathy; MA, myoclonic absence; MA photo+, myoclonic absences with photosensitivity; GTC, generalized tonic-clonic; Fo, focal; M, myoclonic; A, absence; At, atonic; AED, anti-epileptic therapy; FEL, felbamate; VPA, valproic acid; LTG, lamotrigine; LEV, levetiracetam; ETH, ethosuximide; CZP, clonazepam; CBD, cannabidiol; CLB, clobazam; LTG, lamotrigine; OXBZ, oxcarbazepine; Stiri, stiripentol; EEG, electroencephalography; gen., generalized; SW, spike-wave; photo+, photosensitive; PSW, poly-spike and wave; biF, bi-frontal predominance; MRI, magnetic resonance imaging; and ADHD, attention-deficit hyperactivity disorder.

^aBaylor College of Medicine.

^bCENet.

^cGeneDx.

^dOspedale Pediatrico Bambino Gesù.

^eRadboud University Medical Center.