Article Figures & Data
Figures
- Fig 1.
The first row (A) shows axial T2- and T1-weighted images, not obtained in our institution, at the age of 3.5 months. The rows B–D represent MR imaging studies (axial T2-weighted, axial FLAIR, axial T1-weighted precontrast, axial T1-weighted postcontrast) and proton MR spectroscopy studies (long-echo TE, 288; with the voxel placed on the left frontal white matter) performed at our institution at the ages of 8 months, 19 months, and 39 months, respectively. White matter signal-intensity abnormality (high T2-weighted, FLAIR, and low T1-weighted) with frontal predominance involving the arcuate fibers and the external and the extreme capsule is apparent in all studies. The white matter has a swollen appearance in all studies except the last one (D). Basal ganglia symmetric signal-intensity abnormality with patchy appearance involving mainly the caudate and putamen (striatum) is apparent in the first 3 studies. The signal intensity is significantly less in the last study (D). Increasing size of the frontal cavitations is apparent with the subsequent studies. A periventricular rim of high intensity is seen on the T1-weighted images of the studies B–D. Contrast enhancement is less apparent in the last study (D). Spectroscopy results are shown on Table 2.
- Fig 2.
Sequencing chromograms show the C to T base change corresponding to nucleotide 1087 (1087c→t) that was detected on the patient’s GFAP alleles. Both parents tested negative for the presence of the 1087c→t mutation.
- Fig 3.
The figure depicts the location of each of the mild AD–associated mutations in GFAP, in relation to the protein domain structure of intermediate filaments. The protein has a central rod domain that is subdivided into 4 a-helical subdomains separated by nonhelical areas.
Tables
Age Echo Time 1 NAA Cr & PCr Cho mIns Glx Echo Time 2 Lactate 8 months 35 3.9 4.6 1.5 6.0 7.7 288 2.7 19 months 35 3.6 4.3 1.6 6.1 7.6 288 3.3 39 months 35 1.7 4.3 1.9 7.7 7.6 288 4.4 Note:—Concentrations are reported in institutional units (IU). N-acetylaspartate (NAA), creatine and phosphocreatine (Cr & PCr), choline (Cho), myo-inositol (mIns), glutamate/ glutamine (Glx) concentration values are reported from the spectroscopy acquired at an echo time of 35 ms from the left frontal white matter. Lactate concentration values are reported from the spectroscopy acquired at an echo time of 288 ms from the left frontal white matter. Acquisitions used a repetition time of 2000 ms.
- Table 2:
Features of the clinical, neuroimaging, and genetic characteristics of cases of infantile onset Alexander disease associated with mild clinical phenotype
Mutation Sex Age Presentation Age Follow-up Macrocephaly Seizures Spasticity Bulbar signs Cognitive impairment MRI Reference 1* F 7 m 19 y + + + – + T 6 R79C 235 c → t 2* M 3 m 14 y 17 3* M 11 m 7 y 4† 0 m 7.5 y – + –→ + – –→ + T R79H 250 g → a 5† 6 m 20 y – + –→ + – –→ + T 15 6† 6 m 4.7 y – + – – – T 7† F 12 m 8 y 17 8* M Asymptomatic at 4 y – – – – – T 14 R88C 276 c → t 9* M Asymptomatic at 3 y + – – – – T 18 10* 6 m 3.5 y – – – – – T 15 L90P 283 c → t 11†§ F 5 m 5.9 y – + –→ + – –→ + T 16 R239C 716 c → t 12† M 8 m 8 y + + – + + T 13¶ 18 m 8 y – + –→ + – –→ + T 15 A253G 758 g → t 14¶§ M <12 m 8 y – – – + – A 19 15 ¶§ M 1 m – – – – – A 6 L331P 1006 c → t 16¶§ M Asymptomatic + – – – – T 20 17¶§ F Asymptomatic at 7 y – – – – – A A358V 1087 c → t 18† F 3 m 5 y + + – – – T Present R416W 1260 c → t 19* M Asymptomatic at 11 y – – – – – T 14 * Note:— indicates previously proven pathogenic mutation;
† , absence of the mutation in both parents;
¶ , absence of the mutation in one parent;
§ , absence of the mutation in healthy control subjects; m, months; y, years; †, presence; –, absence; T, typical; A, atypical.
