Table 1.

Clinical characteristics of HDLS cases

Family	US 1			US 2	Norwegian		US 3		US 4	US 5	US 6		Germany	US 7		US 8
CSF1R mutation	Met766Thr			Ile775Asn	Gly585_Lys619delinsAla		Glu633Lys		Cys774_Asn814del	Cys774_Asn814delinsQG LQSHVGPSLPSSSPQAQ	Ile794Thr		Ala770Pro	Met875Thr		Gly589Glu
Case #	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16
Age of onset	18	43	27	48	38	36	42	67	50	23	35	57	52	58	71	58
Disease duration	Alive	6	4	Alive	3	4	4	7	5	Alive	Alive	6	11	8	Alive	3
Initial symptom(s)	Depression	Depression/Cognitive impairments	Depression	Left leg stiffness and gait problems	Depression/Cognitive impairments	Depression Cognitive impairments	Impaired dexterity in hand and fingers and bradykinesia	Cognitive impairments/ Personality changes	Cognitive impairments/ Memory problems	Spastic gait	Cognitive impairments	Depression, Personality changes	Cognitive impairments	Cognitive impairments/ Personality changes	Cognitive impairments	Cognitive impairments
Bradykinesia	1	2	2	2	2	2	2	2	2	2	2	2	1	2	2	1
Rigidity	0	2	1	2	0	0	2	2	1	0	0	0	0	0	0	1
Tremor	0	2	1	2	0	0	1	2	0	0	0	1	2	0	0	0
Resting tremor	-	+	-	-	-	-	-	+	-	-	-	-	-	-	-	-
Kinetic or postural tremor	-	+	+	+	-	-	+	+	-	-	-	+	+	-	-	-
Postural instability	0	2	1	2	2	2	2	2	1	1	1	1	1	1	1	2
Gait impairments	1	2	2	2	1	2	2	2	1	2	1	2	2	1	1	2
Shuffling gait	-	+	-	+	-	-	+	+	-	-	-	na	-	-	na	+
Freezing	-	+	-	+	-	-	+	+	-	-	-	na	-	-	na	-
Reduced strides	-	-	+	+	-	-	+	+	-	-	+	na	+	-	na	+
Stooped posture	-	-	-	+	-	+	-	-	-	-	-	na	-	-	na	-
Reduced arm swing	+	+	+	+	na	+	+	-	-	+	+	na	-	-	na	-
Spastic gait	-	-	-	-	-	-	+	-	-	+	-	na	-	-	na	-
Hypomimia	1	2	1	2	1	1	2	2	1	1	1	1	1	1	1	1
Hypophonia	0	2	1	2	0	0	2	2	0	0	0	0	0	0	0	1
Dysarthria	0	2	2	2	0	0	2	2	0	2	0	0	1	na	na	1
Other speech problems¥	0	2	2	1	2	2	2	2	2	2	2	2	2	2	1	2
Dyskinesia	0	0	1פ	0	0	0	0	0	0	0	0	2۵	0	0	0	1פ
Dystonia	0	2	1	0	0	2	1	2	0	0	1	0	0	0	0	2
Myoclonus	0	2	1	0	0	0	0	2	0	0	0	0	2	0	0	1
Chorea	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ataxia	0	na	2L	na	1L	1L	1L	na	na	2SAD	na	na	1L	na	0	na
Spasticity	0	1	0	1	0	0	1	0	0	1	0	na	0	0	na	0
Pyramidal weakness; Initially	0	0	0	0	0	0	1	0	0	0	0	1	1	0	na	0
Pyramidal weakness; Advanced	0	2	1	1	2	2	1	2	2	2	2	1	2	2	1	1
Gegenhalten	0	0	1	0	0	1	0	0	0	0	0	na	0	1	na	1
Cognitive impairments/memory problems	1	2	2	1	2	2	2	2	2	2	2	2	2	2	2	2
Apraxia	0	1a	2b	1	2	2	1	1	2	2	2	2	na	2	1	2
Depression	2	2	1	1	2	2	1	2	2	1	1	2	1	1	1	1
Executive dysfunction	1	2	2	1	2	2	2	2	2	2	2	2	2	2	2	2
Aggressiveness	0	1	0	0	0	0	0	1	1	0	0	1	1	0	0	0
Seizure	-	-	-	-	+β	+β	-	-	-	-	-	+∞	-	-	-	+β
Daytime sleepiness	1	1	1	1	1	1	1	1	1	na	1	1	1	1	1	1
Nighttime sleep disturbance	1	1	1	1	1	1	1	1	1	1	1	2μ	1	1	1	2μ
Eye movement abnormalities	0	na	21	22	21	21	na	13	na	na	13	na	14	na	na	22
Orthostatic hypotension	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urinary/fecal incontinent	0	2	2	2	2	2	2	2	2	0	1	2	2	2	0	2
Clinical diagnosis	LD	LD	LD	PD vs. PSP vs. MS	MS	MS	CBS	CBS	FTD vs. AD vs CADASIL	LD	CADASIL	AD	FTD	FTD vs. AD	FTD	FTD
Criteria for parkinsonism	-	D	D	D	Ps	Ps	D	D	D	Ps	Ps	Ps	Ps	Ps	Ps	D

AD: Alzheimer’s disease; CADASIL: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy; CBS: Corticobasal syndrome; D: Definite; FTD: Frontotemporal dementia; L: Limb; LD: Leukodystrophy of unknown origin; MS: Multiple sclerosis; na: Not available; Ps: Possible; PSP: Progressive supranuclear palsy; SAD: Spastic, ataxic dysarthria;

^¥Defined as aphasia and mutism at the advanced stage of the disease;

^μRestless leg syndrome, the other cases had unspecific sleep problems;

^βGeneralized tonic clonic seizure;

^∞Complexed partial seizure;

¹Homonymous hemianopsia to either right or left side;

²Occulomotor apraxia;

³Poor eye pursuit movements;

⁴Vertical gaze palsy;

^aLimb apraxia;

^bIdeomotor and constructional apraxia;

^cLimb, ideomotor, and constructional apraxia;

^ΩTremor of tongue;

^פGrimacing and tics;

^۵Akathisia.