Table 4:

Clinical information on AxD patients

Patient no.	Mutation	Sex	Onset	First symptom	Highest cognitive	Highest motor	Main deterioration	Age at loss of unassisted walking
1	R70Q	F	40.5	Ataxia	Normal	Walks without support	Gait	No
2	N77S	M	0.16	Frequent arching, seizures	Severe ID	None at all	Severe spasticity, intractable seizures	N/A
3	N77S	F	1	Speech and motor delay	Moderate ID	Walks without support, but wide-based gait	ND	ND
4	N77S, S152L	F	0.58	Seizures	Normal	Walks with support	Motor and language deterioration	Yet to walk without support
5	R79C	M	0.5	Motor delay	Mild ID	Walks without support	Spastic tetraparesis, cognitive problems	14 years
6	R79C	M	0.25	Macrocephaly, developmental delay	Normal	Walks without support	None	No
7	R79C	F	4^*	ND	ND	ND	ND	ND
8	R79C	F	0.5	Developmental delays in speech, walking, hypotonia	Mild–moderate ID	Standing	Facial droop after concussion	Yet to walk without support
9	R79G	F	0.29	Seizures	Severe ID	Sitting without support	Loss of sitting	Never walked without support
10	R79H	F	0.58	Seizure	Mild ID	Walks without support	Ataxia	ND
11	R79H	F	0.5	Arching back and eye rolling upward	Normal	Walks with support	Seizures	Yet to walk without support
12	R79H	F	1.25	Seizure	Moderate ID	Walks without support	Motor skills, cognition	No
13	R79H	F	0	Hypotonia	Severe ID	Reaching for objects	N/A	N/A
14	R79L	M	0.5	Progressive macrocephaly; slowed development	Moderate ID	Walks a few steps without support	None	No
15	R88C	M	4	Short stature, followed by slowed cognitive development	Mild ID	Walks without support	Progressive dysarthria, cognitive delay	No
16	R88C	M	0.75	Macrocephaly, developmental delay	Mild ID	Walks with support	None	Yet to walk without support
17	R88C	M	2	Seizure	Mild ID	Walks without support	Motor decline, seizures, bulbar problems	5 years
18	R88C	M	10	Deterioration in academic skills	Mild ID	Walks without support	Neurocognitive decline and spasticity	No
19	R88C^†	F	10	Vomiting, anorexia	Normal	Walks without support	Scoliosis, gait	30 years

20	R88C^†	M	10	Incoordination	Normal	Walks without support	Scoliosis, gait, some cognitive decline	No
21	R105W^‡	F	6	Memory, math and spelling, behavior	Mild ID	Walks without support	None	No
22	L123P	M	50	Progressive gait problems, inbalance	Normal	Walks without support	Bulbar dysfunction	ND
23	E207Q	M	10.5	Scoliosis, followed by abnormal gait, fatigue, and weakness	Normal	Walks without support	Difficulty walking, urinary incontinence	22 years
24	L231H^†	M	50	Ataxia	Normal	Walks without support	Ataxia	63 years
25	L231H^†	M	na	None	Normal	Walks without support	None	No
26	R239C	M	0.5	Macrocephaly, developmental delay	Severe ID	Standing with support	Swallowing, tone, hydrocephalus	Yet to walk without support
27	R239C	F	1.5	Hypotonia, gross motor delay, macrocephaly	Severe ID	Walks with support	Failure to thrive, emesis, but no regression	Yet to walk without support
28	R239C	F	7	Choking episodes	Mild ID	Walks without support	Gait deterioration, dysarthria, urinary incontinence	No
29	R239C	F	1.67	Intermittent ataxia	Normal	Walks without support	Occasional unsteadiness	No
30	R239H	F	0.29	Vomiting, hypotonia, minimal development	Only social contact	None at all	Progressive bulbar dysfunction	Never walked without support
31	R239H	F	0	Hydrocephalus, minimal development	Severe ID	None	N/A	N/A
32	R239P	M	2	Vomiting, deterioration of gait	Moderate ID	Walks without support	Mild deterioration of gait	No
33	R239P	M	1.5	Speech and motor delay	Mild ID	Walks with support	None	Yet to walk without support
34	S247P	M	10	Severe morning emesis	Normal	Walks without support	Sleep apnea	No
35	R258P	M	0	Macrocephaly, hypotonia	Mild–moderate ID	Walks without support	Seizures, dysarthria, ataxia	No
36	R270-A272del	F	<0.25	Motor delay, macrocephaly	Severe ID	Very limited	N/A	N/A
37	Q290E	F	12	Worsening migraines	Normal	Walks without support	No	No
38	E362Q	F	5	Seizures, ataxia, rigidity	Normal	Normal	Dysarthria, short-term memory, executive function	No
39	E371Q	M	<1	Motor delay	Mild ID	Walks without support	Neurocognitive delay	No
40	E373A	F	34	Numbness, burning sensation	Normal	Normal gait	Fatigue, balance, bladder	No
41	E374G	F	0	Hypotonia, lack of development	Moderate ID	Walks with support	Lost all skills, frequent vomiting	Never walked without support
42	S398F	F	45	Dysarthria	Normal	Walks without support	Ataxia, palatal tremor	No
43	S398Y	F	51^*	MRI after subarachnoid hemorrhage at 51 years, mild urinary urgency at 56 years	Normal	Walks without support	Urinary urge-incontinence, unsteadiness	No
44	M415I^†	F	40	Balance difficulties	Normal	Walks without support	Speech, urinary, headache	No
45	M415I^†, D157N^§	F	4	Ataxia	Normal	Walks without support	Urinary retention, bulbar dysfunction	∼8 years
46	R416W	M	14	Behavior and gait problems; single seizure	Low normal	Walks without support	Ataxia, dysarthria, behavior	18 years
47	R416W	M	13	Dysarthria, dysphagia	Normal	Walks without support	Cognitive impairment, neurogenic bladder, obstructive sleep apnea, palatal tremor	29 years
48	R416W	M	6	Febrile seizure	Low normal	Walks without support	Mild proximal weakness	No
49	R416W	F	16	Balance, bladder	Normal	Walks without support	Balance coordination, weakness, swallowing, hallucinations	No
50	Q426L	F	30	Urinary incontinence, neurogenic bladder	Normal	Normal	Exercise intolerance	45

Information regarding each patient is shown including age of onset, nature of first symptom, highest cognitive level, highest motor level, major deterioration (if any), and age at loss of unassisted walking (if it occurred). All ages are given in years. ID, Intellectual disability; N/A, not applicable; ND, not determined or unknown; F, female; M, male.
↵* Age of onset was estimated.
↵† Parent-child duos are shown together on consecutive lines (19-20, 24-25, and 44-45).
↵‡ The pathogenicity of the R105 mutation is uncertain.
↵§ The D157N mutation is considered a benign variant, but its impact in a compound heterozygote is not known.