Table 1.

Clinical features associated with FGF12 aberrations.

		This study		Willemsen et al (2020)			Siekierska et al (2016)		Takeguchi et al (2018)
		Patient 1	Patient 2	Patient 3	Patient 4	Patient 5 (the mother of patient 4)	Patient 6	Patient 7 (the younger brother of patient 6)	Patient 8	Patient 9
FGF12 aberrations (GRCh38)		Biallelic SVs (Del/Dup) chr3: 192,083,678–192,145,703 (involving exon6, 3′UTR) chr3: 192,330,351–192,499,579 (involving exon 3–4)	NM_004113.6 c.259G>A p.(Glu87Lys) (Homozygous variant)	Heterozygous duplication chr3:192,142,300–192,733,325 (involving exon1-6)	Heterozygous duplication chr3:192,159,179–192,736,896 (involving exon1-5)	Heterozygous duplication chr3:192,159,179–192,736,896 (involving exon1-5)	NM_004113.6 c.155G>A p.(Arg52His) (Heterozygous variant)	NM_004113.6 c.155G>A p.(Arg52His) (Heterozygous variant)	NM_004113.6 c.155G>A p.(Arg52His) (Heterozygous variant)	NM_004113.6 c.155G>A p.(Arg52His) (Heterozygous variant)
Sex		Female	Male	Male	Male	Female	Female	Male	Male	Male
Ethnicity		Japanese	Portuguese and African	N/A	N/A	N/A	Caucasian	Caucasian	Japanese	Japanese
Current age at reported or age at last examination		8 yr 10 mo	Died at 11 yr because of COVID-19 pneumonia	10 yr	3 yr	30 yr	Died at 7 yr because of status epilpticus	Died at 3 yr 6 mo (unknown cause)	33 yr 3 mo	2 yr 6 mo
Seizure type		Generalized tonic-clonic, focal motor, bilateral tonic-clonic, status epilepticus	Epileptic spasm, tonic, myoclonic jerks	Tonic-clonic, atonic, tonic, myoclonic, autonomic	Generalized tonic-clonic, history of febrile seizures, myoclonic jerks	Generalized tonic-clonic	Tonic, combined generalized and focal	Tonic, combined generalized and focal	Focal, tonic	Apnea attack, generalized tonic-clonic, focal seizure with pallor
Interictal EEG		Multifocal, multiple spike, hypsarrhythmia	Multiple discharges, hypsarrhythmia	Slow background, multifocal seizeures	Generalized epileptic activity	Normal	Slow background with multifocal epileptiform discharges, later hypsarrhythmia	Slow background with multifocal epileptiform discharges, later hypsarrhythmia	Suppression burst pattern, later hypsarrhythmia	Slow background with multifocal epileptiformm discharges
AED treatment (current or most recent)		Resistant to AEDs (Valproate, Zonisamide, Phenytoin, Phenobarbital)	Resistant to AEDs (Carbamazepine)	Resistant to AEDs	Valproate	Resistant to AEDs	Resistant to AEDs	Resistant to AEDs	Resistant to AEDs	Resistant to AEDs
Seizure onset	Age at onset	5 mo	5–6 mo	12 mo	13 mo	1 mo	14 d	1 mo	7 d	1 d
	Initial symptom	Spasm, developmental delay	Spasm, developmental delay	Seizures	Febrile convulsion	Seizures	Tonic seizures	Tonic seizures	Seizures	Apnea attack
Development	Head control	None	8 mo	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	Sitting	None	11 mo	N/A	N/A	N/A	24 mo	N/A	None	None at 1 yr 5 mo
	Walking	None	3 yr	Wheelchair dependent	Walk independently (5 yr), uncoordinated gait	Walking with unsteadiness	None	N/A	None	N/A
	Meaningful words	Non verbal	Non verbal	No speech	Clearly speech, but vocabulary reduced	Speech problem	Non verbal	N/A	Non verbal	Non-verbal at 1 yr 5 mo
	Regression	4 mo	No, always delayed but he seems to get worse when seizures are not under control	N/A	None	None	N/A	N/A	N/A	5 mo
Degree of ID		Severe	Moderate	Severe	Moderate	Mild to moderate	Severe	Severe	Severe	Severe
Movement disability		No voluntary movement, myoclonus (hands)	Cerebellar ataxia with occasional dyskenetic movements, spasticity	Ataxia	Unsteady	Unsteady and migraine	Ataxia	Ataxia	Spastic dystonic quadriplegia, dystonic hypertonia of the neck and upper extremities	N/A
Behavioral features		No smile, no eye contact	Autisti-like traits	None	Autism spectrum disorder	None	Stereo types, no eye contact	Stereo types, no eye contact	Stereo types, no eye contact	Poor eye contact
Brain MRI (CT) findings		Almost normal (7 mo), diffuse cerebral atrophy without obvious cerebeller atrophy (1 yr 7 mo)	Normal myelination with a mild cerebral atrophy (12 mo and 1 yr 7 mo), gray matter atrophy with cortical atrophy (6 yr)	Bilateral delayed myelination in the parieto-occipital region	Mild prominence of the subarachnoid space in the frontal regions bilaterally otherwise normal	Normal (CT)	Normal (5 mo), cerebeller atorophy (6 yr)	Normal (2 mo), cerebeller atorophy (3 yr)	Normal (7 yr), mildly enlarged lateral ventricles (13 yr)	Mild cerebral atorophy (6 mo), diffuse cerbral atrophy (1 yr 7 mo)
Other features		Cholecystitis, gallbladder removal at 8 yr	Hypotonia, tremors (early mo∼2 yr), dysmorphic facial features (broad forehead, pointed chin)	Recurrent infection (upper airway), reflux, constipation, feeding difficulties	Dysmorphic facial features	Recurrent infections (perianal abscess, dental infections)	Acquired microcephaly, axial hypotonia, severe feeding difficulties, cerebral visual impairment	Acquired microcephaly, hypotonia, feeding difficulties	Microcephaly, multiple contractures of the extremities in flexion	Microcephaly

Del: intragenic deletion allele, Dup: intragenic tandem duplication allele, AEDs: anti-epileptic drugs, CT: computed tomography, MRI: magnetic resonance imaging, N/A: no assesment.