title: Emergence and nature of mathematical difficulties in young children with Barth syndrome.
abstract: OBJECTIVE
  Barth syndrome (BTHS), a rare X-linked metabolic disorder, is one of the most common known genetic causes of pediatric dilated cardiomyopathy. Advances in the genetic and physical phenotyping of BTHS have surpassed research on its cognitive phenotype. Herein, we expand upon existing knowledge of math difficulties reported for BTHS by evaluating the emergence, nature, and trajectory of mathematics difficulties in this population.
  
  
  METHODS
  We examined neurocognitive performance of 19 young patients from our current and previous studies of BTHS, relative to published normative data. Children completed the Test of Early Mathematics Ability and standardized measures of IQ, visual perception, and vocabulary; executive functions were evaluated by parent report. We focused on subsets of patients to determine whether math difficulties reported for school-aged boys with BTHS appear by preschool (n = 9), whether number sense deficits associated with mathematics learning disability (MLD) are evident in kindergartners with BTHS (n = 10), and whether cognitive skills are stable from preschool to primary school in this population (n = 12).
  
  
  RESULTS
  Preschoolers with BTHS had age-appropriate math, vocabulary, spatial, and IQ scores. Age-appropriate performance was also evident at kindergarten, except for lower math scores. Still, number sense abilities at kindergarten were intact even on items known to predict MLD. The few patients with below average math performance at pre-kindergarten or kindergarten were the only participants whose parents reported early deficits in executive functioning. Performance over time, in math and other domains, was highly variable, such that no single trajectory characterized the phenotype.
  
  
  CONCLUSIONS
  Math difficulties reported earlier for school-aged boys with BTHS are not evident in preschool but appear to emerge by kindergarten. Importantly, kindergartners with BTHS do not demonstrate deficits in early number sense that implicate MLD. Preliminary data suggest that executive functions may underlie or mediate math performance of the few boys with BTHS who are deficient in mathematics, suggesting that BTHS is associated with math difficulties but not math learning disability.
authors.affiliation: Math Skills Development Project, Kennedy Krieger Institute, Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Darcy
authors.initials: D
authors.lastname: Raches
authors.forename: Michèle M M
authors.initials: MM
authors.lastname: Mazzocco
mesh_terms: D056889:Barth Syndrome / Q000235:genetics / Q000503:physiopathology / Q000523:psychology*; D002648:Child; D002657:Child Development / Q000502:physiology*; D002675:Child, Preschool; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology / Q000235:genetics / Q000523:psychology*; D008137:Longitudinal Studies; D008297:Male; D055641:Mathematical Concepts; D009483:Neuropsychological Tests; D014888:Wechsler Scales