Table 1.
Studies reporting macrostructural anatomy in PWS.
| Author | Methods | Sample | Key findings |
|---|---|---|---|
| Cacciari et al. 1990 [9] | MRI—pituitary evaluation only | 1 PWS patient in larger study of 101 patients (15 y) | No abnormality found. |
| Crino et al. 2008 [10] | MRI—pituitary evaluation only | 8 y old male with PWS | No abnormality found. |
| Fan et al. 2005 [15] | Retrospective case reviews of available MRI data | MRI available for 9/10 patients with seizures from total PWS sample of 56 (31 males, 1–37 y) | MRI normal for 8/9; haemorrhage in 1/9. |
| Gilboa & Gross-Tsur 2013 [16] | Retrospective case reviews of available imaging data for patients: MRI, CT, ultrasonography | Imaging data available for 59 of 125 PWS patients (50% male, 1 month–48 y): MRI for 30; CT for 17; ultrasonography for 12 | Abnormalities in 20/59, incl. 4/5 with epilepsy: including ventriculomegaly (3/59); thalamic abnormalities (3/59); partial corpus callosum agenesis (3/59); disturbed myelination (3/59); partial empty sellar (1/59). |
| Grugni et al. 2000 [14] | MRI—pituitary only. | 17 PWS patients (9 males, mean 20 y) | Pituitary hypoplasia (10/17); empty sella (3/17). |
| Hashimoto et al. 1998 [17] | MRI and 1H-MRS | 5 PWS patients (2 males, 1–14.5 y) 37 control infants and children (1–15 y) |
Abnormalities in 5/5: mild ventriculomegaly (4/5); frontal cortical atrophy (3/5); small brainstem (1/5); delayed myelination (1/5). Metabolite abnormalities: Reduced NAA peak in; NAA:Choline and NAA:Creatine ratios tended to be lower in PWS group with a signification relationship between these metabolite rations and developmental level. |
| Hayashi et al. 1992 [18] | Post-mortem | 6 month old female with PWS | No pituitary abnormality; abnormalities of cortical gyrification, cerebellar white matter and dentate gyrus. |
| Honea et al. 2012 [19] | MRI | 23 participants with PWS (8 males, 10–39 y) 25 typically-developing control participants (11 males, 10–48 y) |
Deletion vs. UPD: reduced grey matter volume in PFC & temporal cortex and reduced white matter volume in parietal cortex in deletion; reduced grey and white matter volume in OFC and limbic cortex in UPD. |
| Iughetti et al. 2008 [12] | Retrospective case reviews of available MRI data | 91 children with PWS (49 males, 0.7–16.8 y) | Abnormalities in 61/91: reduced pituitary height (45/91); absence of posterior pituitary bright spot (6/91); ventriculomegaly (8/91); thin corpus callosum (2/91). |
| Kumada et al. 2005 [20] | Retrospective case reviews of available MRI data | Imaging data available for 3/4 patients with PWS and epilepsy (1 males, 3–12 y) in larger study of chromosomal abnormalities and epilepsy | Cerebral atrophy in 1/3. |
| Leonard et al. 1993 [21] | MRI | 4 children with PWS (3 males, 3–10 y) 6 with AS (3 males, 2–7 y) |
Abnormality in sylvian fissure of 1/4 PWS children (unilateral), but 6/6 AS (2 bilateral, 4 unilateral). |
| Linnemann et al. 1999 [11] | MRI case study | 6 y old male with PWS | Small flat pituitary; no further abnormalities. |
| Lukoshe et al. 2013 [22] | MRI | 20 children with PWS (9 males, 6–17 y) 11 sibling control participants (8 males, 7–15 y) |
Significantly reduced brainstem volume in PWS group compared to control group; trend to reduced white matter volume and total cortical surface area in PWS. Greater ventriculomegaly and surface CSF in UPD compared to deletion subtypes. |
| Lukoshe et al. 2014 [23] | MRI | 24 children with PWS (9 males, 6–18 y) 11 sibling control participants (8 males, 7–15 y) |
Decreased cortical complexity in four clusters in frontal, temporal and parietal lobes. Cortical complexity positively correlated with IQ. Greater cortical thickness and lower cortical complexity in some clusters in UPD. |
| Mantoulan et al. 2011 [24] | MRI | 9 PWS teenagers (6 males, 12.7–18.6y, mean 16.4 y) 9 typically developing young adults (6 males, mean 21.2 y) |
No abnormalities found. |
| Maski et al. 2009 [25] | Retrospective case reviews of available “neuroimaging” data: unspecified modality | Imaging data available for 14/21 PWS patients with seizures | Unspecified non-focal abnormalities in 3/14. |
| Miller et al. 1996 [26] | MRI | 15 individuals with PWS (6 males, 2–28 y) 16 age- & sex-matched group with isolated growth hormone deficiency (10 males, 3–14 y) 49 age-matched typically-developing controls from previous literature (1–29 y) |
No significant difference in pituitary height. Posterior pituitary bright spot absent in 3/15 PWS participants and reduced in 1/15. |
| Miller et al. 2006 [27] | MRI | 17 PWS participants (11 males, 4–39 y) 18 individuals with early-onset morbid obesity (EMO) (9 males, 4–22 y) 21 typically-developing siblings (8 males, 3.5–43 y) |
White matter abnormalities in 6/8 adults with PWS and 5 participants with EMO, but 0/9 children with PWS and none in typically-developing controls participants. |
| Miller et al. 2007 [28] | MRI | 27 PWS participants (16 males, 3 m–39 y) 13 EMO participants (4 males, 4–16 y) 26 typically developing siblings (10 males, 2 m–43 y). |
Incomplete insular closure in PWS, compared to both sibling and EMO control groups. |
| Miller et al. 2007 [29] | MRI | 20 PWS participants (12 males, 3 m–39 y) 16 individuals with EMO (8 males, 15 m–22 y) 21 typically-developing siblings (10 males, 2–43 y) |
Abnormalities in all 20 PWS participants: ventriculomegaly (20/20); incomplete closure of the insula (13/20); sylvian fissure polymicrogyria (12/20); decreased parietal-occipital volume (10/20). None of these abnormalities in either EMO or sibling control groups. |
| Miller et al. 2008 [30] | MRI—pituitary evaluation only | 27 individuals with PWS (16 males, 3 m–39 y) 16 individuals with EMO (6 males, 4-22 y) 25 typically-developing siblings (10 males, 2–43 y) |
Pituitary abnormalities in 20/27 PWS, 10/16 EMO & 2/25 controls. Abnormality not specific to PWS. |
| Miller et al. 2009 [31] | MRI | 16 PWS participants (10 males, mean 16.53 y) 12 EMO participants (4 males, mean 9.25 y) 15 typically-developing siblings (5 males, mean 12.08 y) |
Reduced cerebellar volume and cerebellar/cerebral ratio in PWS and EMO compared to sibling group, but no difference between PWS and EMO. |
| Ogura et al. 2011 [32] | MRI | 12 adults with PWS (6 males, 19–31 y) 13 age- & sex-matched controls (6 males, 19–29 y) |
Reduced total brain, grey matter and white matter volume, and focally reduced OFC and somatomotor area volume in PWS. |
| Stevenson et al. 2004 [33] | MRI and post-mortem | Post-mortem: 5 month, 9 month, & 3.5 y old with PWS (2 males) MRI: 9 month old female with PWS |
Cortical grey & white matter abnormalities in 3/4; midbrain, hindbrain & cerebellar abnormalities in 1/4; normal in 1/4. |
| Takeshita et al. 2013 [34] | Retrospective case reviews of available imaging data for patients: MRI, CT | MRI available for 9/31 PWS patients with seizures (6 males, neonatal–3 y) | Diffuse atrophy in 1/9, but appears to have followed some injury to the brain of undisclosed nature. 8/9 within normal limits. |
| Tauber et al. 2000 [13] | Retrospective case reviews of available MRI data—pituitary only | MRI for 16/28 with PWS (mean 11.8 y) | Pituitary hypoplasia in 10/16. |
| van Nieuwpoort et al. 2011 [35] | MRI—pituitary only | 15 adults with PWS (4 males, 19.2–42.9 y) 14 typically-developing siblings (7 males; 17.5–41.3 y) |
Reduced anterior pituitary size in 12/15 adults with PWS compared to sibling group. |
| Vendrame et al. 2010 [36] | Retrospective case reviews of available MRI data | Imaging available for 20/30 PWS patients with seizures (6 males, 4–21 y) | Abnormalities in 5/20: ventriculomegaly (4/20); diffuse cortical atrophy (1/20). |
| Verrotti et al. 2015 [37] | Retrospective case reviews of available imaging data for patients: MRI, CT | Imaging data available for 35/28 PWS patients with seizures (22 males, seizure onset 2 days–11 y, age at imaging evaluation unspecified): MRI for 25; CT for 10 | Abnormalities in 11/35: ventriculomegaly (5/35), cortical atrophy (4/35), corpus callosum hypoplasia (1/35), periventricular leukomalacia (1/35). |
| Yamada et al. 2006 [38] | DTI | 8 participants with PWS (6 males, 8–29 y) 8 age- & sex-matched typically-developing controls (6 males, 8–29 y) |
Atypical diffusivity indicating abnormalities of frontal white matter, posterior limb of internal capsule, and splenium of corpus callosum. |
| Yoshii et al. 2002 [39] | MRI case study | 40 week old female with PWS | Abnormal gyrification and cortical grey-white matter boundaries; partially uncovered right insula. |
AS: Angelman’s syndrome; BMI: body mass index; CSF: cerebrospinal fluid; CT: computerised tomography; DTI: diffusion tnsor imaging; EMO: early-onset morbid obesity; 1H-MRS: proton magnetic resonance spectroscopy; MRI: magnetic resonance imaging; IQ: intelligence quotient; m: months; NAA: N-acetylaspartate; OFC: orbitofrontal cortex; PFC: prefrontal cortex; PWS: Prader-Willi syndrome; UPD: uniparental disomy; y: years.