Table 1 Clinical features of individuals with NUS1 variants

Mutation

c.691 + 1C > A

c.691 + 1C > A

c.691 + 3dupA

c.743delA

c.128_141dup

exon 2 deletion, 1.3 kb

c.869G > A

c.869G > A

Amino acid change

c.601_691del:p.(Arg202Glnfs*9)

c.601_691del:p.(Arg202Glnfs*9)

–

(p.Asp248Alafs*4)

(p.Val48Profs*7)

–

p.Arg290His

p.Arg290His

Zygosity

de novo

de novo

de novo

de novo

de novo

de novo

homozygous

homozygous

Age

17 years

59 years

26 years

8 years 9 months

15 years

29 years

Deceased at 29 months

4 years

Sex

Female

Male

Female

Male

Male

Female

Male

Male

Consanguinity

No

No

N/A

N/A

No

No

N/A

N/A

Ethnicity

Japanese

Japanese

Chinese Han

N/A

French-Canadian

Caucasian

Czechs

Czechs

Birth weight

2826 g (−0.44 SD)

3500 g

N/A

N/A

2489 g

N/A

N/A

N/A

Birth length

N/A

56 cm

N/A

N/A

N/A

N/A

N/A

N/A

Age at seizure onset

9 months

8 years

16 years

12 months

10 months

2.5 years

11 months

7 months

Type of seizures

Febrile seizure at 9 months, generalized tonic-clonic convulsion without fever at 14 months, status epilepticus at 6 years 3 months

Loss of consciousness without convulsion at 8 years

N/A

Generalzed myoclonic epilepsy, convulsive epilepsy, nocturnal jerks

Myoclonic absences with behavioural arrest, facial and palpebral myoclonus

Myoclonic absences with behavioural arrest and eyelid flutters, as well as limb myoclonus

Tonic-clonic seizures, refractory epilepsy and recurrent attacks of “status epilepticus”

Refractory epilepsy, severe seizure

Frequency of seizures

Seizure-free since 6 years of age

N/A

N/A

N/A

5 times a day, lasting 5–10 s

1–2 times a week

N/A

N/A

Type of EEG

3-Hz, diffuse, spike-and-slow-wave, complexed with 7-Hz, slow wave background

8–9 Hz slow α rhythm background with no epileptiform activity

N/A

Bifrontal epileptiform activity

Diffuse background slowing, with rhythmic, bifrontal, high-amplitude theta discharges

Generalized spike-wave and poly-spike wave activity

N/A

N/A

Effective medicines for seizures

Valproic acid was effective for seizures, levetiracetam lessened 3-Hz, diffuse, spike-and-slow wave complexes

Myoclonus lessened with 50 mg baclofen

N/A

Levetiracetam

N/A

Relatively well-controlled with a combination of valproic acid, lamotrigine and clonazepam

N/A

N/A

Brain MRI

Normal at 20 months,slight cerebellaratrophy at 14 years

Normal

Normal

Normal (2 years 3 months)

Normal (8 years)

Normal

N/A

Severe cortical atrophy

Intellectual disability

Mild to moderate

Moderate

N/A

Moderate

Moderate

Mild

Yes

N/A

Language delay

Mild (speaking two-word sentences at 2 years)

Yes

No

Yes

Mild

No

N/A

N/A

Developmental delay

Mild psychomotor delay

No

N/A

Yes

Yes

Mild motor delay

Yes

N/A

Ataxia

Yes

Yes

N/A

Yes

No

No

N/A

N/A

Autsim

No

No

N/A

N/A

Yes

N/A

N/A

N/A

Scoliosis

Yes (operation at 15 years of age)

Yes

N/A

N/A

N/A

N/A

Yes, congenital

Yes, congenital

Hypotonia

No

No

N/A

N/A

N/A

N/A

Severe

Severe

Dysmorphic features

No

No

N/A

N/A

No

N/A

Microcephaly

Microcephaly

Additional features

Dysgraphia due to tremulous myoclonus of bilateral extremities

Eye pursuits were saccadic, hyperkinesie volitionelle-like movement, cortical myoclonus

Parkinson’s disease, asymmetric onset, bradykinesia, resting tremor in limbs, mild gait difficulties

–

–

Eye pursuits were saccadic, but saccades were normal

Histophathological examination of autopsy tissue revealed non-specific neuronal loss in brain cortex and cerebellum

–