Table 1.
Clinical Characteristics of Patients and Mutations Detected in EIF2B2, EIF2B4, and EIF2B5[Note]
|
Patient Number |
||||||||
| Characteristic | 941-1a | 941-2a | 944 | 992 | 943a | 871 | 948 | 1014 |
| Age at examination | 23 | 24 | 33 | 16 | 29 | 31 | 48 | 16 |
| Development: | ||||||||
| Walking at age (mo) | 18 | 12 | 12 | 12 | 12 | 12 | 17 | 12 |
| Speech | Delayed | Normal | Normal | Normal | Delayed | Normal | Normal | Normal |
| Education | DS | DS | DS | DS | DS | HS graduate | HS teacher | HS student |
| Ovarian function: | ||||||||
| Menarche at age | NA | 16b | 14c | NA | NA | 13d | 14 | 14 |
| Amenorrhea at age | NA | NA | 26 | NA | NA | 27 | 31 | 16 |
| Size of ovariese | Atrophied | Atrophied | Atrophied | ND | Atrophied | ND | Normal | ND |
| Neurologic signs: | ||||||||
| Spasticity | + | + | + | ++ | − | + | + | − |
| Gait instability at age | 10 | 15 | 25 | 10 | NO | 27 | 30 | NO |
| Walker use at age | NO | 16 | 30 | 16 | NO | NO | NO | NO |
| Dysarthria at age | NO | 20 | NO | 14 | NO | NO | NO | NO |
| Sphincter dysfunction at age | NO | 20 | 26 | NO | NO | NO | 30 | NO |
| Optic atrophy | + | + | + | − | − | − | − | − |
| Other | +f | − | − | − | +g | − | − | − |
| Acute episodes at age | NO | NO | 28 (visual loss) | NO | NO | 31 (recurrent headaches) | 3 (simple seizures) | NO |
| Cognitive function | IQ = 77 at age 15; IQ = 79 at age 23; VMD; speed processing | IQ = 60 at age 16; IQ = 66 at age 24; VMD; attention deficit | IQ = 60 at age 29; IQ= 65 at age 30; VMD; poor executive function | IQ not evaluated; no deterioration | IQ = 80 at age 6; IQ = 52 at age 28; frontal lobe syndrome | IQ not evaluated; slow with anxiety and depression at age 27 | Mini mental status = 21/30 at age 45 | IQ = 96 at age 16 |
| Alive | Yes | Yes | Yes | Yes | Yes | Noh | Yes | Yes |
| Mutated gene | EIF2B4 | EIF2B4 | EIF2B2 | EIF2B2 | NI | EIF2B5 | EIF2B5 | EIF2B5 |
| Nucleotide changesi | C1393T, C1465T | C1393T, C1465T | C512T, 607-12del/insTG | C547T, A638G | NI | G338A, G338A | G338A, G338A | G338A, C583T |
| Amino acid changesj | C465R, Y489H | C465R, Y489H | S171F, M203fs | R183stop, E213G | NI | R113H, R113H | R113H, R113H | R113H, R195C |
Note.— Age is shown in years, except as otherwise noted. + = spasticity; ++ = severe spasticity; − = none; DS = difficulties in school; fs = frameshift; HS = high school; NA = not applicable; ND = not determined; NI = not identified; NO = not observed; VMD = visual motor difficulties.
Three patients were reported elsewhere (Schiffmann et al. 1997); patient 941-1 reported as patient 1, patient 941-2 as patient 2, and patient 943 as patient 3.
Patient 941-1 had irregular menses at ∼6-mo intervals.
Patient 944 had with irregular menses and was treated with a combination of estrogen and progesterone.
Patient 871 had a first-trimester spontaneous abortion at age 22 years.
Ovaries observed by use of pelvic ultrasonography.
Patient 941-1 experienced fine motor difficulties at age 23 years.
Patient 943 experienced left facial weakness.
Patient 871 died of status epilepticus at age 32 years.
For the nucleotide changes, numbering starts with A of ATG start codon.
For the amino acid changes, numbering starts with first methionine. R113H = mutation of arginine to histidine.