Research Notes: Summary of Findings in Prader-Willi Syndrome

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Brain imaging

• Miller 2007 Mar (n=20)
  • ventriculomegaly (100% - 20/20)
  • decreased volume of brain tissue in parietal-occipital lobe (50%)
  • sylvian fissure polymicrogyria (60%)
  • incomplete insular closure (65%)
• Hashimoto 1998 (n=5)
  • slight ventriculomegaly (100%)
  • cortical atrophy (100% - 5/5)
  • small brainstem (100%)
  • decreased N-acetylaspartate/Choline (NAA/Cho) ratio (20% - 1/5)
  • decreased N-acetylaspartate/Creatine (NAA/Cr) ratio (40% - 2/5)
  • normal Choline/Creatine (Cho/Cr) ratio (100%)
• Leonard 1993 (PWS=4, Angelman=6)
  • length of Sylvian fissure banks were anomalous in 12% of PWS, 75% of Angelman children
• Titomanlio 2006 (report)
  • right cerebellar hemisphere hypoplasia
• Yoshii 2002
  • abnormal cortical development
• Civardi 2004 (n=21)
  • higher motor threshold
  • normal central motor conduction time, central silent period, and F waves
  • significantly reduced intracortical facilitation
  • PWS-del had weaker intracortical inhibition compared to PWS-upd
  • "Transcranial magnetic stimulation [first dorsal interosseous muscle] changes in patients with PWS suggested a hypo-excitability of the motor cortical areas. Defective neurogenesis of the cortical tissue and multiple transmitter alterations are the putative causes. Impaired intracortical inhibition might represent an electrical marker for a deletion defect."
• Yamada 2006 (n=8)
  • significantly higher trace value in left frontal white matter
  • significantly higher trace value in left dorsomedial thalamus
  • significantly reduced fractional anisotropy in posterior limb of internal capsule bilaterally
  • significantly reduced fractional anisotropy in right frontal white matter
  • significantly reduced fractional anisotropy in splenium of corpus callosum
• Kusuhara 1996
  • bilateral middle cerebral artery occlusion (stroke) and moyamoya phenomenon in 19-yr-old male w/ NIDDM

Endocrinological

• Pituitary
  • Miller 2007 Apr (n=27)
    • pituitary morphological abnormalities (74% PWS, 69% EMO, 8% controls) but did not correlate with anterior pituitary hormone deficiencies
    • low IGF-1 (100%)
    • central hypothyroidism (19%)
    • hypoplastic genitalia or hypogonadotropic hypogonadism (100%)
  • Miller 1996 (n=15 w/ GHD)
    • no statistically significant difference in height of anterior pituitary gland in PWS compared to children w/o PWS or children with isolated GHD
    • complete absence of posterior pituitary bright spot (PPBS) (20%)
    • small PPBS (1)
  • Cacciari 1990 (n=1)
    • normal MRI of sella turcica
  • Linnemann 1999 (report)
    • central precocious puberty and empty sella syndrome

Hematological

• Factor XI deficiency (Futterweit 1986)
• Factor IX deficiency (Murken 1966)
• von Willebrand's disease (anecdotal)
• blood clotting "problems" including petechiae (anecdotal)

Hypothalamus

• Normal leptin secretion (Goldstone 2004)
• Long isoform leptin receptor mRNA expressed in lymphocytes (Goldstone 2004)
• Increased fasting plasma ghrelin (Goldstone 2004)
• Reduced post-prandial secretion of pancreatic polypeptide (Goldstone 2004)
• Reduced fasting and post-prandial insulin secretion (Goldstone 2004)
• Normal cholecystokinin secretion (Goldstone 2004)
• Normal distribution of neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelamocortin (POMC) and growth hormone releasing hormone (GHRH) neurons in infundibular nucleus (INF) (Goldstone 2004)
• Normal colocalization of NPY and AGRP in INF neurons (Goldstone 2004)
• Normal increase in NPY, measured by either immunocytochemical (ICC) staining or mRNA expression, or AGRP (ICC staining) in INF during illness (Goldstone 2004)
• Reduced NPY (either ICC staining or mRNA expression) in INF, compared with control, but not nonPWS obese adults, corrected for duration of premorbid illness (Goldstone 2004)
• Normal AGRP (ICC staining) in INF, compared to control and nonPWS obese adults (corrected for duration of premorbid illness) (Goldstone 2004)
• Normal increase in the number of GHRH neurons in the INF during illness (Goldstone 2004)
• Normal number of GHRH neurons in the INF compared to control and nonPWS obese adults (corrected for duration of premorbid illness and gender) (Goldstone 2004)
• Reduced number of GHRH neurons in INF in children receiving GH treatment (Goldstone 2004)
• Normal distribution of oxytocin and vasopressin neurons in paraventricular nucleus (PVN) (Goldstone 2004)
• Reduced number of total (38%) and oxytocin (42%)-containing neurons in PVN (Goldstone 2004)
• Normal number of vasopressin-containing neurons in PVN (Goldstone 2004)
• Normal distribution of neurons that contain cocaine- and amphetamine-regulated transcript (CART) in INF, PVN and lateral hypothalamic area (LHA) (Goldstone 2004)
• CART neurons in INF, PVN and LHA not complete (Goldstone 2004)
• Deficiency of POMC-containing neurons in INF (Goldstone 2004)
• Reduced number of luteinising hormone releasing hormone-containing neurons in pre-optic area and oxytocin-containing neurons in PVN in Ndn-knockout mice (Goldstone 2004)