Table 1:

Phenotypic spectrum of SYNJ1 epileptic encephalopathy (early infantile epileptic encephalopathy-53)

										Our reported patient
	Consanguineous family from Pakistan5	Siblings from a consanguineous family of Moroccan origin6		Consanguineous family from Moroccan origin6		Non-consanguineous Caucasian couple. Only one affected had genetic testing.6		Consanguineous family from Emirati family of Omani origin7		Consanguineous family from Saudi Arabian origin
	homozygous c.406C>T, p.Arg136	homozygous c.2663A>G, p.Tyr888Cys		homozygous c.2528G>A, p.Trp843		Compound heterozygous c.1938delT, p.Gln647Argfs*6 and c.3365-2A>G, p.Ser1122Thrfs*6		homozygous c.709C>T, p.Gln237		homozygous c.858_862delACAAA
	Boy	Girl	Boy	Girl	Girl	Boy	Boy	Girl	Boy	Girl
Intellectual impairment	Profound delay	Profound delay	Profound delay	Profound delay	Profound delay	Profound delay	Profound delay	Severe delay	Profound delay	Profound delay
Seizure	Clusters of tonic seizures, tonic- clonic seizures from day 9 of life	Flexion spasm at 10 months (may have started at 2.5 months) Developed myoclonic and tonic seizures	Epileptic spasms at 6 months Developed myoclonic and tonic seizures	Clonic seizure during day 1 of life and then developed myoclonic and tonic-clonic seizure	Clonic seizure during day 1 of life and then developed myoclonic and tonic-clonic seizure	Eye blinking and shoulder movement from Day 12 of life and then evolved into myoclonic and tonic-clonic type	Eye deviation from Day 1 of life and then refractory GTC and myoclonic seizures	Lip smacking and tonic seizures from D2 of life	Epileptic spasms, tonic clonic seizures, and myoclonus	Multifocal seizures from 2 days of age. Later developed epileptic spasms and myoclonic seizures
EEG	Modified hypsarrhythmia	modified hypsarrhythmia or multifocal epileptic activity on a slow background	modified hypsarrhythmia or multifocal epileptic activity on a slow background	modified hypsarrhythmia or focal spikes on a slow background	modified hypsarrhythmia or focal spikes on a slow background	Multifocal epileptiform activity in a slow background	Multifocal epileptiform activity in a slow background	Hypsarrhythmia	Hypsarrhythmia	modified hypsarrhythmia or multifocal epileptic activity on a slow background
Brain MRI	Mild cerebral atrophy at 5 years of age	normal	normal	normal	normal	normal	thin corpus callosum and limited gliosis and atrophy of the periventricular white matter	normal	Mild dilatation of ventricles and subarachnoid spaces	normal
Dystonia	Not available	no	no	no	no	yes	Yes	no	no	Yes
Parkinsonism	Not available	no	no	no	no	no	no	no	no	no
Other clinical features	Progressive neurodegenerative course, feeding intolerance, and G tube dependence, hypotonia progressed to multiple contractures, cortical blindness, Death at age 6 years	Progressive neurodegenerative course, feeding intolerance, and G tube dependence, hypotonia progressed to spastic quadriparesis, cortical visual impairment	Progressive neurodegenerative course, feeding intolerance, and G tube dependence, hypotonia progressed to spastic quadriparesis, cortical visual impairment	Progressive spastic quadriplegia and feeding problem	Progressive spastic quadriplegia and feeding problem	Progressive neurodegenerative course, feeding intolerance, and G tube dependence, hypotonia progressed to hypetonia to opisthotonus, Death at the age of 2.5 years	Progressive neurodegenerative course with death at the age of 8 years, spastic quadriparesis, cotical visual impairment, feeding dysfunction	Both developed acquired microcephaly and axial hypotnia and girl child had scoliosis	Hypotonia progressed to spastic quadriparesis, feeding intolerance and G tube dependence
Other features	Decreased complex I activity and predominance of type 2 fibers in the muscle biopsy, tau- immunoreactive neurofibrillary degeneration in the substantia nigra			high lactate, combined deficiency in complex III and IV activity in liver and fibroblasts	Increased creatine kinase