title: Corpus callosum measurements correlate with developmental delay in Smith-Lemli-Opitz syndrome.
abstract: BACKGROUND
  Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation, neurodevelopmental disorder of cholesterol metabolism caused by mutations in 7-dehydrocholesterol reductase. Corpus callosum (CC) malformations and developmental delay are common, but the relation between the two has not been evaluated. This study hypothesizes shorter callosal length and smaller area correlate with higher serum 7-dehydrocholesterol and increased severity of neurodevelopmental delay in SLOS.
  
  
  METHODS
  Thirty-six individuals with SLOS (18M/18F) between 0.20 and 12.5 years (mean = 3.9, SD = 3.6) and 36 typically developing controls (18 boys and 18 girls) between 0.12 and 12.8 years (mean = 4.0, SD = 3.6) were each imaged once on a 1.5T scanner. One midsagittal image per study was selected for manual CC measurement. Gross motor, fine motor, and language developmental quotients; anatomical severity score; and serum sterol levels were assessed.
  
  
  RESULTS
  Shorter CC length and smaller area correlated with a lower developmental quotient in gross motor and language domains. Furthermore, length and area negatively correlated with a serum sterol precursors and severity score, and positively correlated with total cholesterol. Degree of developmental delay ranged from mild to severe, involving all domains.
  
  
  CONCLUSIONS
  For individuals with SLOS, smaller callosal area and length are associated with higher 7-dehydrocholesterol, severity scores, and developmental delay. The relationship between callosal development and biochemical abnormalities in this cohort may lead to further studies supporting imaging biomarkers.
authors.affiliation: Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland, USA. leer@kennedykrieger.org
authors.forename: Ryan W Y
authors.initials: RW
authors.lastname: Lee
authors.forename: Shoko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Eun Sol
authors.initials: ES
authors.lastname: Jung
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Eva H
authors.initials: EH
authors.lastname: Baker
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology*; D002658:Developmental Disabilities / Q000150:complications* / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism; D019082:Smith-Lemli-Opitz Syndrome / Q000473:pathology*
chemical_list: D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase