Introduction
Methods
Results
Frequency of biallelic RFC1 expansions
Phenotypic characterization of the RFC1-related DBN syndrome
RFC1-positive group (n = 15) | (GAA)≥200-FGF14-positive group (n = 102) | Genetically unexplained group (n = 50) | RFC1-positive vs GAA-FGF14-positive | RFC1-positive vs genetically unexplained | |
---|---|---|---|---|---|
p value | p value | ||||
Male sex | 7 (74%) | 55 (54%) | 31 (62%) | – | – |
Age at disease onset | 63.5 (44–78) | 67 (30–84) | 67 (17–88) | 0.080 | 0.262 |
Disease duration | 7 (4–18) | 6 (0–26.5) | 4 (0–50) | 0.070 | 0.007 |
Age at last examination | 72 (52–91) | 74.5 (40–92) | 72 (21–89) | 0.210 | 0.878 |
Positive family history | 4/15 (27%) | 35/102 (34%) | 7/49 (14%) | 0.771 | 0.268 |
FARS disability stagea | 3.25 (1.5–4) | 3 (1.5–5) | 2 (1–4) | 0.042 | 0.003 |
History of falls | 8/9 (89%) | 35/64 (55%) | 10/23 (43%) | 0.072 | 0.044 |
Regular use of walking aid | 7/14 (50%) | 19/99 (19%) | 7/49 (14%) | 0.017 | 0.009 |
Symptoms | |||||
Episodic symptoms | 0/14 (0%) | 11/100 (11%) | 18/49 (37%) | 0.354 | 0.006 |
Postural instability | 15/15 (100%) | 101/101 (100%) | 50/50 (100%) | 1.000 | 1.000 |
Visual disturbances | 9/15 (60%) | 55/102 (54%) | 20/50 (40%) | 0.784 | 0.238 |
Fine motor impairment | 3/14 (21%) | 13/98 (13%) | 8/49 (16%) | 0.419 | 0.419 |
Speech impairment | 3/15 (20%) | 17/100 (17%) | 8/48 (17%) | 0.723 | 0.714 |
Swallowing difficulties | 1/15 (7%) | 7/100 (7%) | 4/49 (8%) | 1.000 | 1.000 |
Sensory symptoms | 5/15 (33%) | 13/100 (13%) | 7/49 (14%) | 0.058 | 0.132 |
Autonomic symptoms | 3/15 (20%) | 9/101 (9%) | 3/48 (6%) | 0.187 | 0.141 |
Clinical signs | |||||
Impaired balance/gait | 15/15 (100%) | 80/98 (82%) | 27/46 (59%) | 0.123 | 0.003 |
Positive Romberg test | 12/13 (92%) | 48/87 (55%) | 15/38 (39%) | 0.013 | 0.001 |
Cerebellar ocular motor signs | |||||
Gaze–evoked nystagmus | 10/15 (67%) | 68/102 (67%) | 30/49 (61%) | 1.000 | 0.769 |
Saccadic pursuit | 15/15 (100%) | 100/101 (99%) | 41/49 (84%) | 1.000 | 0.181 |
Dysmetric saccades | 6/15 (40%) | 28/99 (28%) | 14/49 (29%) | 0.374 | 0.526 |
Cerebellar ataxia | |||||
Ataxia of upper limbs | 8/14 (57%) | 17/87 (20%) | 11/38 (29%) | 0.005 | 0.103 |
Dysdiadochokinesia | 5/13 (38%) | 16/87 (18%) | 9/40 (22%) | 0.139 | 0.292 |
Dysarthria | 4/15 (27%) | 14/99 (14%) | 6/45 (13%) | 0.252 | 0.250 |
Neuropathy | |||||
Impaired vibration at ankle (≤ 3/8) | 11/14 (79%) | 17/97 (18%) | 11/48 (23%) | < 0.001 | < 0.001 |
Ankle hyporeflexia | 10/14 (71%) | 24/97 (25%) | 17/48 (35%) | < 0.001 | 0.030 |
Pyramidal tract signs | 0/14 (0%) | 1/95 (1%) | 1/49 (2%) | 1.000 | 1.000 |
Parkinsonism | 2/14 (14%) | 13/97 (13%) | 10/49 (20%) | 1.000 | 1.000 |
MRI | |||||
Disease duration at last MRI | 6 (5–15) | 4 (0–17) | 2 (− 3–50) | 0.013 | 0.007 |
Vermis atrophy | 4/11 (36%) | 9/71 (13%) | 5/33 (15%) | 0.068 | 0.195 |
Cerebellar hemisphere atrophy | 3/11 (27%) | 5/71 (7%) | 4/33 (12%) | 0.070 | 0.341 |
Brainstem atrophy | 1/11 (9%) | 0/70 (0%) | 1/33 (3%) | 0.136 | 0.442 |
Nerve conduction studies | |||||
Abnormal sural SNAP | 6/6 (100%) | 10/20 (50%) | 3/3 (100%) | 0.157 | 1.000 |
Abnormal upper limb SNAP | 4/4 (100%) | 1/10 (10%) | 0/2 (0%) | 0.005 | 0.067 |
Abnormal CMAP (any nerve) | 2/5 (40%) | 7/20 (35%) | 3/3 (100%) | 1.000 | 0.196 |
Vestibular function evaluation—caloric stimulation, vHIT, rotatory chair | |||||
Bilateral vestibulopathy | 15/15 (100%) | 11/97 (11%) | 5/45 (11%) | < 0.001 | < 0.001 |
VOR gain on vHIT in BVP—mean (± SD) | 0.15 (± 0.11) | 0.39 (± 0.15) | 0.50 (± 0.07) | 0.004 | 0.036 |
Response to 4-aminopyridine treatment | |||||
Clinician-reported response | 1/6 (17%) | 33/41 (80%) | 4/9 (44%) | 0.004 | 0.580 |
Patient-reported response | 1/7 (14%) | 32/54 (59%) | 1/11 (9%) | 0.041 | 1.000 |