Table 1.
| Twins A and B | Proband of Family 1 in James, et al. (5) | Average CMT2D phenotype | Average dSMA V phenotype | |
|---|---|---|---|---|
| Onset | Infantile | 6 months | 2nd decade (4,9) | 2nd decade (3) |
| 1st Symptoms | No spontaneous movement of feet or toes. Gross developmental delay with some regression of skills. |
“floppy” feet | Hand weakness +/− cramping and pain (9) | UE in 6/9 LE in 1/9 UE+LE in 2/9 (3) |
| Inheritance | De novo | De novo | Autosomal Dominant or de novo | Autosomal Dominant or de novo |
| Mutation with location | GARS: G652A in Anticodon Binding Domain | GARS: G598A in Anticodon Binding Domain |
GARS: G240R, E71G, P244L, I280F, D500N, S581L. Predominantly in catalytic domain, centered around the dimer interface (3,7) |
GARS: L129P, E71G, H418R, G526, D500N. BSCL2: N88S (3) |
| Distal axonal neuropathy with UE>LE | UE symptoms = LE symptoms | No, LE symptoms > UE symptoms | Yes, but 20/20 developed bilateral foot and peroneal weakness and atrophy within an average of 3.3 yrs after hand atrophy (9) | 8/12 with UE+LE motor deficits 6/12 with UE+LE atrophy (3) |
| Course | Slowly Progressive | Slow-to-moderate progression | Slowly Progressive | Slowly Progressive |
| Limited use of fingers/hands | Yes: finger extension difficult; impaired grip | Yes: impaired finger grip at age 7 yrs | Reported intrinsic hand muscle wasting, but no clear report of decreased hand function | Reported intrinsic hand muscle wasting, but no clear report of decreased hand function |
| Pes Cavus | No, flat feet | No, flat feet | 16/20 (9) | 5/12 subjects (3); 4/38 (9) |
| LE Distal Wasting | Yes--at 2 yrs | Yes--at 3 yrs | 7/20 (9) | 1/12 subjects (3); 12/40 (9) |
| UE DTRs | 1–2+ | Absent | Absent (4) | Absent in 5/12 (3) |
| LE DTRs | Absent | Absent | Absent or decreased in 17/20 (4,9) | Absent or decreased in 1/12 (3); 25/40 (9) |
| Pyramidal Signs | No | No | None or rare (8,9) | 5/40 (9); “Some” (3); “Common” (8) |
| Sensory Signs | None to date (4 years) | None by age 7 years | Yes: vibration deficits common in most CMT2D patients; decreased touch, pain, and temperature sensation in some (9) | Rarely, but in advanced stages of disease--average of 30 yrs after symptom onset (8,9) |
| Hyperlordosis | Yes (severe in Twin B) | Yes, severe | None Reported | None Reported |
| Scoliosis | No in Twin A; Yes in Twin B | Yes | Reported in some: 4/60 (9) | 3/12 (3) |
| Independent Ambulation | Not to date, but walk with AFOs and reverse walker | No | Yes, but 5/60 developed need for assistance in advanced stages of disease (9) |