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.