Table VII:
Imaging genetics studies in intellectual disability syndromes (fragile X syndrome (FMR1), tuberous sclerosis (TSC1 and TSC2), neurofibromatosis type 1 (NF1), and Rett syndrome (MECP2)). No studies for Timothy syndrome (CACNA1C) were retrieved in our search of the literature.
| Disorder | Gene | Imaging modality | Imaging phenotype | Samples size (mean age in years) | Primary results (main effect of genotype) | Reference |
|---|---|---|---|---|---|---|
| Fragile X syndrome | FMR1 full mutation | sMRI | Quantitative morphometry | Subgroups of 51 FXS; 120 HC | ↑ CN volume, and lateral ventricle (in males). | (Reiss et al. 1995) |
| Hippocampus and amygdala volume | 10 FXS (5 ‡ (6.3); 5 † (9.0)); 10 HC (5 ‡ (6.4); 5 † (8.7)) | ↑ Right hippocampal volume. | (Kates et al. 1997) | |||
| Regional brain volumes | 10 FXS (9.0); 10 HC (8.5) | ↑ CN and ventricular volumes. | (Kaplan et al. 1997) | |||
| Tissue volumes | 10 FXS (9.1); 10 HC (8.5) | ↑ CN GM volume. | (Reiss et al. 1998) | |||
| TBM | 36 FXS (14.66); 33 HC (14.67) | ↑ CN and lateral ventricle volumes, and trend-level parietal and temporal WM ↑. | (Lee et al. 2007) | |||
| GM VBM and manual tracing; multivariate pattern classification | 51 FXS (35 months); 32 HC (29.7 months); 18 DD (34.8 months) ‡ | ↓ GM volumes in regions including hypothalamus, insula, medial and lateral PFC. Spatial patterns that discriminated FXS from other groups included a medial to lateral gradient of increased and decreased regional brain volumes in posterior vermis, amygdala, and hippocampus. |
(Hoeft et al. 2008) | |||
| CN, hippocampus, putamen, amygdala volume | 52 FXS (2.9); 63 ASD (2.8); 19 DD (3,0); 31 HC (2.6) ‡ | ↑ CN volume compared to all control groups. FXS: ↓ amygdala volume. ASD:↑ amygdala volume. |
(Hazlett et al. 2009) | |||
| VBM of regional GM | 10 FXS (28.9); 10 ASD (30.1); 10 HC (29.4) | FXS: ↑ GM volumes within frontal, parietal, temporal, and cingulate gyri, and in CN and cerebellum compared to ASD. FXS: ↑ GM volumes in frontal gyri and CN and ↓ GM volumes in cerebellar, parietal and temporal regions compared to HC. ASD: ↑ GM volumes in frontal and temporal gyri compared to FXS and ↓ GM cerebellar volumes compared to HC. |
(Wilson et al. 2009) | |||
| Total and regional insular volumes | 11 FXS (5 † (15.3); 6 ‡ (16.3)); 8 HC ((5 † (16.5); 3 ‡ (13.3)); 11 DD (6 † (16.4); 5 ‡ (16.0)) | ↓ Total, anterior and posterior insular volumes compared to HC and DD. | (Cohen et al. 2011) | |||
| Univariate VBM; multivariate pattern classification and clustering. | 52 FXS (2.90); 63 ASD (2.77); 31 HC (2.55); 19 DD (2.96) ‡ | ↓ (for FXS) and ↑ (for ASD) volumes of frontal and temporal GM and WM regions (including medial PFC, OFC, superior temporal region, temporal pole, amygdala, insula, and dorsal cingulum) compared to HC. Overall pattern of brain structure in ASD resembles that of HC more than FXS. |
(Hoeft et al. 2011) | |||
| Regional brain bulk volumes (stereology) and GM and WM volume (VBM) | 17 FXS (30); 18 HC (35) ‡ | ↑ CN, parietal lobes and right brainstem bulk volume. ↓ Left frontal lobe volume. ↑ GM volumes of fronto-striatal regions including CN. ↑ WM in regions extending from brainstem to parahippocampal gyrus, and from left cingulate cortex to CC. |
(Hallahan et al. 2011) | |||
| Age-related change in regional brain volumes | 59 FXS (36 † (16.0); 23 ‡ (15.2)) (19 with longitudinal data); 83 HC (47 † (15.8); 36 ‡ (15.5)) (17 with longitudinal data) | Consistent FXS related volume differences in CN compared to HC across adolescence. Aberrant maturation of PFC gyri. | (Bray et al. 2011) | |||
| Cortical volume, thickness, complexity, surface area and gyrification index | 11 FXS (9.16) (6 FXS; 5 FXS+ASD); 10 HC (8.25) ‡ | FXS: ↑Cortical volume, thickness and complexity compared to HC. FXS+ASD: ↑ Left parietal lobe volume, ↓ gyrification specifically in the left temporal and a trend for ↓ right frontal surface area compared to FXS. |
(Meguid et al. 2012) | |||
| Total brain, regional (lobar) and subcortical volumes; brain growth | 53 FXS (2.9); 68 ASD (2.8); 19 DD (3.0); 31 HC (2.6) ‡ | FXS: ↑ Global brain volumes compared to HC but not ASD. ↑ Temporal lobe WM, cerebellar GM, and CN volume compared to ASD. ↓ Amygdala volume compared to ASD. Rate of brain growth from 2 to 5 years similar to HC. |
(Hazlett et al. 2012) | |||
| Relationship repetitive behaviors and CN volume | 41 FXS (4.6) (16 FXS+ASD (4.8)); 30 ASD (4.7) ‡ | FXS: Positive correlation of self-injury with CN volume. ASD: Positive correlation of compulsive behaviors with CN volume. |
(Wolff et al. 2013) | |||
| CN volume and topography | 48 FXS (21.3); 28 IQ-matched controls (19.5); 36 HC (19.7) | ↑ CN compared to both control groups, with ↑ bilateral CN radial distance, ↑ dorsolateral CN head and ventromedial CN body radial distances. | (Peng et al. 2014) | |||
| CN and hippocampal volume | 14 FXS+ASD (22.6); 17 HI (22.0); 25 HC (21.6) ‡ | FXS: ↑ Hippocampus and CN volume compared to HC. HI: ↓ Hippocampal volumes. |
(Molnar and Keri 2014) | |||
| DTI | Whole-brain, frontal-caudate, and sensory-motor tract FA | 10 FXS (16.7); 10 HC (17.1) † | ↓ FA in WM in fronto-striatal pathways and parietal sensory-motor tracts. | (Barnea-Goraly et al. 2003) | ||
| Ventral frontostriatal WM | 17 FXS (2.8); 13 HC (2.3); 8 DD (3.0) ‡ | ↑ Density of fibers localized in left ventral frontostriatal pathway. | (Haas et al. 2009) | |||
| Voxel-based comparison of anisotropy and diffusivity | 18 FXS (11.01); 25 22q11.2DS (10.75); 17 TS (10.56); 41 HC (10.6) † | FXS: ↓ FA in posterior limbs of internal capsule, posterior thalami, and precentral gyrus. | (Villalon-Reina et al. 2013) | |||
| sMRI | GM density (VBM) | 17 FXS (17.5); 16 HC (16.3) | ↑ GM density in bilateral caudate head, left hippocampus, left planum temporale, left angular gyrus, and left superior parietal lobule. ↓ GM density in bilateral insular cortex, precuneus cortex, thalamus, and subgenual cingulate cortex. |
(Hall et al. 2013) | ||
| rs-fMRI | Fractional Amplitude (fALFF); functional connectivity (group ICA and dual regression) | ↓ Functional connectivity in salience, precuneus, left executive control, language, and visuospatial networks. ↓fALFF in bilateral insular, precuneus, and ACC. |
||||
| fMRI | ROI activation during 1-back and 2-back visuospatial working memory tasks | 10 FXS; 15 HC † | No change in activation between 1-back and 2-back tasks in IFG, middle frontal gyrus, superior parietal lobule, and supramarginal gyrus, while HCs showed ↑ activation. | (Kwon et al. 2001) | ||
| Activation during a counting Stroop task | 14 FXS; 14 HC † (15.4) † | ↓ Activation in orbitofrontal gyrus, insular cortex, superior temporal gyrus. No activation in inferior/superior parietal lobe as seen in HC. |
(Tamm et al. 2002) | |||
| FG and STS activation in response to face and gaze stimuli | 11 FXS (16.4); 11 HC (15.5) † | ↓ Left STS activation to all stimuli. No greater FG activation to forward faces compared to angled faces as seen in HC. |
(Garrett et al. 2004) | |||
| Go/nogo task | 10 FXS (15.4); 10 DD (14.6); 10 HC (16.7) ‡ | ↓ Activation in right ventrolateral PFC and right caudate head, and ↑ left ventrolateral PFC activation compared with both control groups. Positive correlation between task performance and activation in left ventrolateral PFC. |
(Hoeft et al. 2007) | |||
| Emotional attribution task | 10 FXS (16.4); 10 HC (15.6) † | ↓ ACC activation for neutral compared to scrambled faces. ↓ CN activation for sad compared to scrambled faces. FXS: ↑ Negative correlation between IQ and insula activation for neutral compared to scrambled faces. HC: ↑ Positive correlation between IQ and ACC activation for neutral compared to scrambled faces. |
(Hagan et al. 2008) | |||
| Activation during face encoding | 11 FXS (18.5); 11 HC (18.7) | ↓ Activation of prefrontal regions including medial and superior frontal cortex during successful face encoding. Negative correlation social anxiety and brain activity during face encoding. | (Holsen et al. 2008) | |||
| Whole-brain and ROI activation during directed or averted eye gaze stimuli | 13 FXS (15.5); 10 DD (16.1); 13 HC (15.0) ‡ | ↓ PFC activation and ↑ left insula activation to direct eye gaze stimuli. ↑ Sensitization in left amygdala with successive exposure to direct gaze compared to controls. |
(Watson et al. 2008) | |||
| Auditory temporal discrimination task | 10 FXS (18.7); 10 HC (14.7) † | ↑ Activation in a left-lateralized network including left medial frontal gyrus, left superior and middle temporal gyrus, left cerebellum, and left brainstem (pons). | (Hall et al. 2009) | |||
| Brain activity during a gaze habituation task | 30 FXS (20.9); 25 HC (19.0) | ↓ Neural habituation and significant sensitization in cingulated gyrus, fusiform gyrus and frontal cortex in response to gaze stimuli. | (Bruno et al. 2014) | |||
| Neurofibromatosis type 1 | NF1 | sMRI | Cerebral GM and WM | 22 NF1; 20 HC | ↑ Brain volume, especially WM. | (Said et al. 1996) |
| Number, volume, distribution and change in time of UBOs | 46 NF1 (7.8) (28‡; 18†) | UBOs found in 93% of subjects, localized most commonly in GP (30.4%), cerebellum (23.5%), and midbrain (16.2%). ↑ UBO number and volume between 4 to 10 years with a reduction in subjects aged 10+ years. |
(Griffiths et al. 1999) | |||
| 24 ventricular and parenchymal dimensions and area calculations | 27 NF1 (8.8) (20‡; 7†); 43 HC (5.9) (22‡;21†) | ↑ Bicaudate width, biatrial width, and biparietal diameter, but not hemispheric length. ↑ Iter measures, descending sigmoid sinus, and ↑ brainstem height (age-specific). |
(DiMario et al. 1999) | |||
| TBV, GM, WM, CSF, CC regions and hyperintensities | 52 NF1 (10.9); 19 HC (9.8) | ↑ TBV due to ↑ GM volume. ↑ CC size. ↑ Group differences in GM to WM ratio in younger compared to older subjects. |
(Moore et al. 2000) | |||
| Morphometric and volumetric measures of (midline) structures; GM and WM volume | 18 NF1 (range 6.2-14.7); 60 HC (range 4.5-16.1) | ↑ Bilateral hyperintensities and ↑ midline structure size in macrocephalic compared to normocephalic NF1. ↑ Brain volume and WM volume but not GM or ventricular volume in macrocephalic subjects compared to HC. |
(Steen et al. 2001) | |||
| Surface area, GM volume, and asymmetry of the PT and PP | 24 NF1 (11.1); 24HC (11.8) | ↓ Left PT surface area and GM volume and ↑ symmetry between left and right PT in NF1 boys compared to NF1 girls and HC. | (Billingsley et al. 2002) | |||
| Number of affected regions, UBO volume and number | 12 NF1 (13.0) | UBO prevalent in GP/internal capsule. ↓UBO locations, number and/or volume for all regions except cerebellar hemispheres between ages 7 to 12 years and ↑ during adolescence. |
(Kraut et al. 2004) | |||
| GM and WM volumes | 36 NF1 (9.3); 39 HC (9.5) | ↑ GM volumes predominantly in temporal, parietal and occipital regions and WM volumes predominantly in frontal lobe. | (Greenwood et al. 2005) | |||
| Frequency, signal characteristics and localization of T2 hyperintensities at different ages | 103 NF1 (13.9) | ↓ Frequency, size, and intensity of T2 hyperintensities in BG and cerebellum/brainstem with age. No differences in hemispheric lesions with age. |
(Gill et al. 2006) | |||
| Regional subcortical volumes; cortical volume, thickness, surface area and gyrification | 14 NF1 (11.3); 14 HC (11.9) | ↑ Volume of thalami, right CN and middle CC. ↓ Gyrification indices in frontal and temporal lobes, insula, cingulate cortex, parietal and occipital regions. No differences in cortical volume, thickness and surface area. |
(Violante et al. 2013) | |||
| SVM; VBM | 21 NF1 (11.1); 29 HC; 18 NF1 (33.1); 31 HC (35.0) | SVM classifiers correctly classified 94% of cases (sensitivity 92%; specificity 96%). | (Duarte et al. 2014) | |||
| GM and WM volume | 16 NF1 (29.8); 16 HC (33.1) | ↓ GM volume of superior frontal gyrus, orbital gyrus and right STG ↑ GM volume in frontal, temporal,,parietal and limbic lobes |
(Pride et al. 2014) | |||
| sMRI | TBV; CC morphology | 10 NF1 (range 20-68): 10 HC (range 21-64) | No differences in TBV. ↑ CC length (10%), CC area (20%). |
(Wignall et al. 2010) | ||
| DTI | CC diffusion characteristics | ↑ Minor eigenvalues at genu of CC. | ||||
| GM and WM volume | 14 NF1 (24); 12 HC (22.7) | ↑ GM and WM volume. | (Karlsgodt et al. 2012) | |||
| TBSS | ↓ FA and radial diffusion and ↑ ADC with greatest magnitude in frontal lobe. | |||||
| DTI | FA and ADC brainstem, basal ganglia, thalamus, CC, and frontal and parietooccipital WM regions | 10 NF1 (25.8); 10 HC (26.3) | ↑ ADC and ↓ FA in all regions of interest. | (Zamboni et al. 2007) | ||
| Diffusion characteristics (ADC, FA, A(m), eigenvalues) healthy and disordered brain matter | 50 NF1 ((21 female (12.2); 29 male (12.3)); 8 HC | ↑ ADC and eigenvalues in UBO compared to normal-appearing sites ↑ ADC in normal-appearing sites compared to HC. No differences in FA or A(m) in most regions. |
(van Engelen et al. 2008) | |||
| FA BG, cerebellum, pons, thalamus | 44 NF1(12.8); 20 HC (14.1) | ↓ Bilateral cerebellar and thalamic FA. | (Ferraz-Filho et al. 2012) | |||
| FA, ADC CN, putamen, GP, thalamus | 14 NF1 (16.3) (8 with UBOs; 6 without UBOs and 9 <18 years;5 > 18 years); 8 HC (16.1) | ↑ ADC in CN, putamen, GP, thalamus. | (Nicita et al. 2014) | |||
| ADC,FA, RD, eigenvalues for 7 GM and 8WM ROIs; WM trajectories for adjacent WM tracts of NBOs | 14 NF1 (7.2); HC | ↑ ADC and eigenvalues in GM and WM UBOs compared to contralateral normal-appearing sites and HC and ↓ FA compared to HC. Three out of 18 UBOs disrupt WM tracts. ↑ADC, lambda(2) and radial diffusivity of WM UBOs in patients with neurological symptoms compared to patients without. |
(Ertan et al. 2014) | |||
| fMRI | Activity in ten ROIs during phonologic processing | 15 NF1 (14.4); 15 HC (15.3) | Inferior and dorsolateral PFC activation relative to posterior activation ↑ during auditory phonologic processing and ↓ during orthographic processing. | (Billingsley et al. 2003) | ||
| Occipital and parietal cortex activity during visual-spatial processing | 15 NF1 (14.4); 15 HC (15.3) | ↑ Posterior cortex activation relative to lateral and inferior frontal activation. | (Billingsley et al. 2004) | |||
| Activation in frontal, temporal, parietal, and occipital regions during visuospatial processing | 13 NF1 (9.8); 13 HC (9.8) | ↑ Left instead of right hemisphere activation. ↓ Activation in primary visual cortex. |
(Clements-Stephens et al. 2008) | |||
| Early cortical visual pathway and DN activation during visual stimuli activating magnocellular and parvocellular pathways | 15 NF1 (11.7); 24 HC (12.0); 13 NF1 (33.1)†; 15 HC (32.7)† | ↓ Activation of low-level visual cortex. ↓ Deactivation or ↑ activation of midline regions of DN during magnocellular- biased stimulation. |
(Violante et al. 2012) | |||
| rs-fMRI | Ventral ACC, amygdala, OFC, PCC RSFC | 14 NF1 (12.5); 30 HC (12.3) | ↑ Connectivity between: left ventral ACC and frontal cortex, insula, and subcortical areas (CN, putamen); left amygdala and frontal cortex, insula, supramarginal gyrus, and PCC/precuneus; left OFC and frontal and subcortical areas (CN, pallidum). | (Loitfelder et al. 2015) | ||
| Tuberous sclerosis complex | TSC1/TSC2 | sMRI | Number and location of cerebellar tubers and volumes of underlying parenchyma | 34 TSC (8.9) | Mean tuber number was 14.3 and 44.1% of subjects showed both cerebral and cerebellar tubers and had more global cortical lesions than subjects with cerebral tubers only. ↓ Focal volume associated with tubers in cerebellum. |
(Marti-Bonmati et al. 2000) |
| GM, WM and CSF volume | 10 TSC (41.5); 8 HC (40.0) | ↓ GM volume in medial temporal lobes, posterior cingulate gyrus, thalamus, BG and right fronto-parietal cortex. ↓ Of limbic and subcortical GM volume negatively correlated with tuber count. ↓ WM of longitudinal fasciculi and other major intrahemispheric tracts. ↑ Cerebellar WM. |
(Ridler et al. 2001) | |||
| Tuber distribution and lesion load | 25 TSC (39.0) | Highest tuber frequency in frontal lobes and highest tuber density in parietal regions with variation in tuber density but no lateralization of tubers. Nodules were located predominantly in CN. Tuber and nodule volumes positively correlated. ↑ Tuber volume in subjects with a history of epilepsy. |
(Ridler et al. 2004) | |||
| Characteristics of cerebellar lesions | 73 TSC (range 0-28 years) | 16.4% of TSC subjects showed cerebellar lesions. Six subjects showed atrophy of cerebellar parenchyma around tubers. | (Jurkiewicz et al. 2006) | |||
| GM, WM and CSF volume and lesion load | 25 TSC (39.3); 25 HC (34.3) | ↓ Subcortical GM volume in regions including thalamus, BG, insula, and cerebellum. ↓ WM in intrahemispheric tracts. |
(Ridler et al. 2007) | |||
| Tuber number and tuber/brain proportion | 58 TSC (20.6) (19 TSC1 (25.0); 34 TSC2 (19.0)) | ↑ Tubers and tuber/brain proportion in TSC2 compared to TSC1 subjects and in subjects with a mutation deleting or directly inactivating tuberin GAP domain compared to subjects with an intact GAP domain. | (Jansen et al. 2008a) | |||
| Tuber number and tuber/brain proportion as determinants of seizures and cognitive function | 61 TSC (17.9) (14 TSC1; 30 TSC2) | Tuber/brain proportion was inversely related to age at seizure onset and intelligence. | (Jansen et al. 2008b) | |||
| Presence of SENs and SGCTs | 81 TSC (28) | 15% of TSC subjects showed SGCTs. 62% showed SENs, 24% of which also showed SGCTs. ↑ SGCT volume at follow-up. |
(Michelozzi et al. 2013) | |||
| Cerebellar volume | 36 TSC (9.7)(19 TSC2; 7 TSC1); HC (9.7) | ↓ Cerebellar volume, with strongest effect in subjects with TSC2 mutations. | (Weisenfeld et al. 2013) | |||
| (Cyst-like) tuber/ brain proportion and tuber number in relation to age at seizure onset | 23 TSC (12.4) | Tuber/brain proportion and number of tubers, but not cyst-like tuber/brain proportion and number of cyst-like tubers, were negatively correlated with age at seizure onset. | (Nakata et al. 2013) | |||
| DTI | ADC, FA of epileptogenic tubers | 15 TSC | ↑ ADC values in subtuber WM in epileptogenic tubers compared to nonepileptogenic tubers. | (Chandra et al. 2006) | ||
| ADC of NAWM in frontal, parietal and occipital lobes, and pons | 23 TSC (12); 18 HC | ↑ ADC values in frontal WM and pons for age group between 96 and 144 months and in right parietal and occipital WM for subjects older than 144 months. | (Arulrajah et al. 2009) | |||
| ADC, FA in tubers and WM lesions | 14 TSC (15.1) | ↑ ADC values in cortical tubers. ↑ ADC values and ↓ FA values in WM lesions compared with contralateral regions. |
(Piao et al. 2009) | |||
| FA, diffusion characteristics in ROIs in or adjacent to cortical tubers in epileptogenic and non-epileptogenic zones | 12 TSC (8.2) | ↓ FA of cortical tubers in epileptogenic compared to non-epileptogenic zones. ↑ Radial diffusivity and ↓ FA in NAWM in epileptogenic zones compared to non-epileptogenic zones. |
(Widjaja et al. 2010) | |||
| FA, trace, eigenvalues CC and internal capsules, in relation to tuber load | 12 TSC (9.2); 23 HC (11.1) | Tubers were found in frontal lobes (144), parietal lobes (64), temporal lobes (42), occipital lobes (57) and insular cortex (7). ↓ FA, ↑ trace and average lambda(3) in CC and ↑ trace in internal capsules. Tuber volume correlated with multiple DTI characteristics in CC and internal capsules. |
(Simao et al. 2010) | |||
| Diffusion characteristics geniculocalcarine tract, internal capsule, temporal gyri and splenium of the CC | 10 TSC (range 1.5-25 years); 6 HC (range 1.1-25 years) | ↓ FA in geniculocalcarine tracts and splenium of CC. ↓ Axial diffusivity in internal capsule, STG, and geniculocalcarine tracts. ↑ Mean and radial diffusivity in splenium of CC. |
(Krishnan et al. 2010) | |||
| FA, mean radial and axial diffusivities of CC | 40 TSC (7.2) (12 with ASD); 29 HC (7.7) | ↓ Average FA and ↑ diffusivity values in CC. ↓ Average FA in TSC +ASD subjects compared to HC and TSC −ASD subjects (who showed no differences). |
(Peters et al. 2012) | |||
| Diffusion characteristics in major tracts | 16 TSC (13.0); 12 HC (15.3) | ↓ FA and axial diffusivity in wide-spread WM regions. ↓ Number of fibers and number of tract points of commissural fibers, projection fibers and major WM tracts. |
(Wong et al. 2013) | |||
| Diffusion characteristics of RMLs, tubers, SENs, cerebellar lesions and SGCT and NAWM | 30 TSC (15.5); 16 HC (7 children (9); 9 adults (36)) | Mean of 47 RMLs, 27 tubers, and 10 SENs per TSC subject. Inverse correlation of RML FA and MD. No differences NAWM FA and MD. |
(van Eeghen et al. 2013) | |||
| FA dorsal language circuit tract | 38 TSC (10 TSC + ASD; 17 TSC − ASD); 24 HC | ↓ FA values in dorsal language circuit tract. ↓ FA in WM close to Geschwind’s territory and WM close to Broca’s area in TSC +ASD compared to TSC −ASD subjects. |
(Taquet et al. 2014) | |||
| FA, ADC, axial and radial diffusivity of tubers and WM lesions | 18 TSC (9.3) | ↓ FA and ↑ ADC and axial and radial diffusivity values in tubers compared to contralateral normal regions. ↑ Radial diffusivity and ↓ FA in WM lesions. |
(Dogan et al. 2015) | |||
| Global and regional WM connectivity | 20 TSC (range 3-24 years)(11 TSC+ DD; 9 TSC − DD; 20 HC (range 2-23 years) | ↓ Interhemispheric connectivity. ↑ MD, positively correlated with tuber load severity. ↑ MD in TSC + DD subjects compared to TSC – DD subjects. |
(Im et al. 2015) | |||
| Rett syndrome | MECP | sMRI | TBV, cortical GM and WM, subcortical gray nuclei, CSF volumes | 11 RTT (10.1); 15 HC (11.2) † | ↓ Cerebral volume ↑ Loss of GM in comparison to WM, with largest decrease in frontal regions and CN and midbrain volume. |
(Reiss et al. 1993) |
| TBV, cortical GM and WM, subcortical GM, CSF and posterior fossa volumes | 20 RTT (9.8); 20 HC (9.0) † | ↓ GM volume most pronounced in prefrontal, posterior-frontal, and anterior-temporal regions. ↓ WM volume uniformly throughout brain. ↓ CN volume. No differences in midbrain volumes. |
(Subramaniam et al. 1997) | |||
| Absolute and relative changes in GM and WM volumes | 23 RTT (8.6) (12 more severe (8.8); 10 less severe (8.3)); 25 HC (8.9)† | ↓ Absolute volume throughout the brain ↓ Relative parietal lobe GM volume, particularly dorsal. ↓ Cortical WM volume. ↓ Anterior frontal lobe volumes in more severely affected subjects. |
(Carter et al. 2008) | |||
| DTI | Regional FA | 32 RTT (5.5); 37 HC (6.1)† | ↓ FA in genu and splenium of CC and external capsule, and regions of cingulate, internal capsule, posterior thalamic radiation, and frontal WM. No differences in visual pathways. ↓ FA in superior longitudinal fasciculus in patients who were nonverbal or speaking only single words. |
(Mahmood et al. 2010) | ||
22q11.2DS= 22.q11.2 deletion syndrome, ACC= anterior cingulate cortex, ADC= apparent diffusion coefficient, A(m)= axial anisotropy, ASD= autism spectrum disorder, BG=basal gangli, CC= corpus callosum, CN= caudate nucleus, CSF= cerebrospinal fluid, DD= developmental delay, DN= default network, DTI = diffusion tensor imaging, FA= fractional anisotropy, fALFF = fractional amplitude of low-frequency fluctuations, FG= fusiform gyrus, fMRI= functional MRI, FXS= fragile X syndrome, GAP= GTPase activating protein, GM= grey matter, GP= globus pallidum, HI= hypoxic injury, IFG= inferior frontal gyrus, IPL= inferior parietal lobule, IPS= intraparietal sulcus, MCP= middle cerebellar peduncle, MD= mean diffusivity, MTI=magnetization transfer imaging, NAWM= normal-appearing white matter, NF1= neurofibromatosis 1, OFC= orbitofrontal cortex, PCC= posterior cingulate cortex, PFC= prefrontal cortex, PP= planum parietale, PT= planum temporale, RML= radial migration lines, ROI= region of interest, RSFC= resting state functional connectivity; RTT= Rett syndrome, SCP= superior cerebellar peduncle, SEN= subependymal nodule, SGCT= subependymal giant cell tumour, sMRI= structural MRI, STG= superior temporal gyrus, STS= superior temporal sulcus, SVM= support vector machines, SWM= spatial working memory, T1= timepoint 1, T2= timepoint 2, TBM = tensor-based morphometry, TBV= total brain volume, TPJ= temporoparietal junction, TS= turner syndrome, TSC= tuberous sclerosis, TWM = temporal working memory, UBO = unidentified bright objects, VBM= voxel based morphometry, WM= white matter
†
female
‡
male