Table 1.

Clinical, imaging and electrophysiological features of SYNE1 patients

Patient ID	Phenotype category	Genotype (cDNA)	Origin/ gender	SARA score	SDFS	Age of onset	First clinical symptom	Age at last examin ation (years)	Cerebellar ataxia	Dysfunction upper motor neuron	Dysfunction lower motor neuron	Additional clinical features	Cerebellar atrophy (MRI)	Peripheral neuropathy (NCS)	EMG changes (muscle)	Abnormal MEPs
1-1	Ataxia MND	c.18583C>T; c.18583C>T;	Turkey/m	10	2	17	Fasciculations face	25	+; onset 20 yrs	+ signs; no spasticity	Fasciculations face		+	n	Anterior tibial and deltoid muscle: acute and chronic denervation	Prolonged UL + LL
1-2	Ataxia MND	c.18583C > T; c.18583C > T;	Turkey/m	23	3	11	Speech disturbance	28	+; onset 17 yrs	+ signs; no spasticity	+ thenar and hypothenar atrophy; fibrillation tongue	CK elevation (257U/l), pes equinovarus,	+	Tibial CMAP amplitude reduced	Anterior tibial and deltoid muscle: acute and chronic denervation	Prolonged UL + LL
2-1	Ataxia MND	c.23554_23555delCA; c.4732C > T	Belgium/f	14	5	6	Mild spasticity LL	28	+; onset 15yrs	+ signs; no spasticity	+ thenar atrophy (4-/5), mainly proximal in LL (4/5)	Unilateral diaphragm paralysis left with restrictive lung function, CK elevation (341 U/L),	n (age 22 years)	Reduced CMAP amplitudes LL; normal SNAP	Chronic denervation proximal and distal PSW, fibrillation potentials	n.d.
3-1	Ataxia MND	c.24814C > T c.13567_13570delGAAG	Turkey/f	19	6	28	Gait disturbance	37	+; onset 28yrs	+ signs; mild spasticity	-	Downbeat nystagmus	+	n	n	Normal UL, LL
4-1	Ataxia cognition	c.15029_15032delAGGA; c.15438 + 2T > A	Germany/f	14.5	4	42	Gait disturbance	49	+; onset 42yrs	-	-	Cognitive impairment: attention, memory, executive function	+	n	n	Normal UL, LL
5-1	Ataxia MND	c.10379_10380delAT; c.10996_ 11003delCTGGACGA	Germany/m	13	3	23	Gait disturbance	44	+; onset 23yrs	+ spasticity	fasciculations and atrophy tongue	Writer's cramp, polyneuropathy	+	Reduced sural SNAP and SNCV, normal tibial NCS	n.d.	n.d.
6-1	Ataxia MND cognition	c.1903dupA; c.1903dupA	Italy/m	9,5	2	7	Cognitive deficits; gait disturbance	35	+; onset 7 yrs	+ signs; spasticity	-	Cognitive impairment: attention, memory, executive function; impaired colour vision; urinary dysfunction; depression	+	n.d.	n.d.	n
7-1	Ataxia MND	c.25655delG; c.21971C > A	Italy/m	20	3	6	Speech and gait disturbance	27	+; onset 6 yrs	+ signs; spasticity	distal atrophy UL and LL	Hammer-toes, motor polyneuropathy	+	Reduced CMAP, normal, SNAP	Acute denervation LL and UL	n.d.

Patient ID = family number_individual number; ataxia MND = cerebellar ataxia plus motor neuron disease involving upper and/or lower neuron damage; m = male; f = female; + = present; - = absent; SARA = scale for the assessment and rating of ataxia; SDFS = spinocerebellar degeneration functional score, assessing disability stage from 1 to 7 (0: no functional handicap; 1: no functional handicap but signs at examination; 2: mild, able to run, walking unlimited; 3: moderate, unable to run, limited walking without help; 4: severe, walking with one stick; 5: walking with two sticks; 6: unable to walk, requiring wheelchair; 7: confined to the bed); upper motor neuron signs = extensor plantar response positive and/or hyperreflexia of muscle tendon reflexes; UL = upper limb, LL = lower limb; CK = creatine kinase; NCS = nerve conduction studies; CMAP = compound muscle action potential; SNAP = sensory nerve action potential; SNCV = sensory nerve conduction velocity; EMG = electromyography; MEP = motor evoked potentials; PSW = positive sharp waves; n.d. = not done; n = normal.