Table 1. Clinical summary of the patients with ATP1A3 variants and polymicrogyria.
DQ, developmental quotient; EEG, electroencephalogram; CT, computed tomography; MRI, magnetic resonance imaging.
| Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| Familial occurrence | Sporadic | Sporadic | Sporadic | Sporadic | Sporadic | Sporadic | Sporadic | Sporadic |
|
ATP1A3 mutation (NM_152296.4) |
c.2976_ 2978del, p.(Asp992del) de novo |
c.2976_2978del, p.(Asp992del) de novo |
c.2972_2982delins TTGCGCAT CTTCATCTG, p.(Tyr4_Ile994delins PheAlaHisLeuHisLeu) de novo |
c.2975_2983dup, p.(Ile994_ Arg995ins HisGluIle) de novo |
c.2570_2572del, p.(Phe857del) de novo |
c.2560_ 2568del, p.(Gly854_Phe856del) de novo |
c.1787G>A, p.(Cys596Tyr) de novo |
c.2684A>C, p.(Gln895Pro) de novo |
| Ethnicity | Japanese | Japanese | Japanese | Japanese | Israeli | Japanese | Japanese | Japanese |
| Age | 3 years 10 months |
1 year 4 months |
7 years 0 months | 5 years 9 months |
2 years 6 months (deceased at 3 years) |
10 years 9 months |
5 years 0 months |
6 years 10 months |
| Sex | Male | Female | Male | Female | Female | Male | Female | Male |
| Clinical diagnosis | Perisylvian polymicrogyria |
Frontoparietal polymicrogyria |
Frontoparietal polymicrogyria |
Frontoparietal polymicrogyria |
Perisylvian polymicrogyria |
Frontoparietal polymicrogyria |
Perisylvian polymicrogyria |
Perisylvian polymicrogyria |
| Gestation | 37 weeks | 35 weeks | 39 weeks | 38 weeks | 35 weeks | 37 weeks | 41 weeks | 40 weeks |
| Birth length | 40.0 cm (−2.92 SD) |
40.0 cm (−2.24 SD) |
48.0 cm (−0.46 SD) |
43.6 cm (−2.38 SD) |
Unknown | 49.5 cm (+1.01 SD) |
Unknown | 49.0 cm (−0.00 SD) |
| Birth weight | 2152 g (−1.53 SD) |
2450 g (+0.17 SD) |
2754 g (−1.01 SD) |
2622 g (−0.82 SD) |
1820 g (10th–25th percentile) |
2928 g (+0.76 SD) |
2822 g (−0.91 SD) |
3438 g (+0.68 SD) |
| Birth head circumference |
32.0 cm (−0.48 SD) |
32.0 cm (+0.47 SD) |
31.0 cm (−1.64 SD) |
31.5 cm (−1.21 SD) |
30 cm (10th percentile) |
33.0 cm (+0.17 SD) |
31.5 cm (−1.67 SD) |
33.0 cm (−0.49 SD) |
| Facial dysmorphism | No | No | Retrognathia and partial cleft palate |
No | No | No | Telecanthus and micrognathia |
No |
| Other malformations |
Hypo pigmented brownish hair |
No | Bell-shaped narrow chest, single transverse palmar crease |
No | No | No | No | No |
| Seizure onset | 30 s | Soon after birth | 3 days | 10 min | 4 days | 1 hour | 2 days | No |
| Seizure types | Tonic convulsions, clonic convulsions, eye deviation, eye blinking, and twitching of the corner of the mouth |
Generalized tonic-clonic seizures |
Right-side dominant tonic-clonic convulsions, tonic seizures, focal or generalized clonic seizures, and autonomic seizures |
Focal motor seizures and autonomic seizures |
Generalized seizures starting with increased tonus in the left hand and foot, the head and eyes turn to the left, and sometimes, the body becomes tonic and clonic |
Apneic spells and tonic seizures |
Eye opening and nystagmus with bilateral extremity quivering and facial stiffening, followed by irregular respiration and cyanosis |
No |
| EEG findings | Suppression burst at 1 month and multifocal spikes at 2 years |
Frequent multifocal sharp waves with diffuse slow waves |
Interictal: frequent sharp waves on T3 propagating to the left hemisphere; ictal: rhythmic activity at T3 or F4 to C4 |
Bilateral frontal sharp waves with decreased background activity |
Abnormal background activity and slow delta waves |
Bilateral spikes with a background of slow waves |
Multifocal epileptic discharges with a background of continuous diffuse slow waves |
Normal at 3 months |
| Prognosis of seizures |
Intractable, hourly |
Seizure-free | Intractable, daily | Intractable, hourly |
Intractable, partially controlled |
Intractable, daily |
Intractable, daily |
Seizure-free |
| Development | No social smile, no head control, DQ < 10 |
No social smile, no head control |
No social smile, no head control, DQ = 2.5 |
No social smile, no head control |
No eye contact, no head control |
No social smile, no head control, DQ < 10 |
No social smile, no head control, DQ < 10 |
No meaningful words, no rolling over |
| Intracranial calcifications on CT |
No | Yes | No | No | Unknown | No | No | No |
| Brain MRI findings |
Poly microgyria |
Poly microgyria |
Poly microgyria |
Poly microgyria |
Poly microgyria |
Poly microgyria |
Poly microgyria |
Poly microgyria |
| Progressive brain atrophy |
Yes | Unknown | Yes | Yes | Unknown | Cerebellar vermis only |
No | No |
| Laboratory findings | Hypo thyroidism |
Normal | Normal | Normal | Normal | Normal | Normal | Normal |
| Other characteristic features |
Congestive cardiac failure during tachycardia |
Episodic tachycardia, right hearing impairment, and tracheostomy at 3 months |
Recurrent cardiac failure in early infancy |
Coagulation abnormalities induced by phenobarbital, requiring mechanical ventilation |
No | No | No | Severe spastic quadriplegia |
|
Diagnostic criteria of AHC | ||||||||
| Repeated attacks of hemiplegia or quadriparesis |
No | No | No | No | No | No | No | No |
| Relief from symptoms upon sleep |
No | No | No | No | No | No | Unknown | No |
| Involuntary movement such as choreoathetosis, dystonia, or ataxia |
No | No | No | No | No | No | No | Dystonia |
|
Supporting feature of AHC | ||||||||
| Repeated attacks of monocular nystagmus |
No | No | No | No | No | No | No | No |
|
Diagnostic criteria of RDP | ||||||||
| Parkinson’s disease | No | No | No | No | No | No | No | No |
| Clear rostrocaudal gradient of involvement |
No | No | No | No | No | No | Unknown | No |
| Prominent bulbar findings on examination |
No | No | No | No | No | No | No | No |
|
Diagnostic criteria of CAPOS | ||||||||
| Cerebellar ataxia | Unknown | Unknown (no voluntary movement) |
No | Unknown (no voluntary movement) |
No | No | Unknown | No |
| Areflexia | Yes | No | Yes | No | No | No | No | No |
| Pes cavus | No | No | No | No | No | No | No | No |
| Optic nerve atrophy | No | Unknown | Unknown | Unknown | No, but cortical blindness |
No | No | No |
| Sensorineural hearing loss |
Yes | Unknown | Unknown | Unknown | No, but normal auditory brainstem response |
No | Yes | No |