Pseudohypacusis in childhood and adolescence is associated with increased gray matter volume in the medial frontal gyrus and superior temporal gyrus

Pseudohypacusis is a somatoform disorder characterized by hearing loss with discrepancies between pure-tone audiometry and auditory brainstem response (ABR), but the underlying neuronal mechanisms remain unclear. Using voxel-based morphometry (VBM) with magnetic resonance (MR) imaging for 14 unmedicated, right-handed patients and 35 healthy control subjects, we investigated whether functional hearing loss was associated with discernible changes of brain morphology. Group differences in gray matter volume (GMV) were assessed using high-resolution, T1-weighted, volumetric MR imaging datasets (3T Trio scanner; Siemens AG) and analyzed with covariant factors of age, sex, socioeconomic status (SES), and total GMV, which was increased by 27.9% in the left medial frontal gyrus (MFG) (Brodmann area 10) (p=.001, corrected cluster level) and by 14.4% in the right superior temporal gyrus (STG) and the adjacent middle temporal gyrus (MTG) (BA42 to 21) (p=.009, corrected cluster level) in patients with pseudohypacusis. The GMV in the right STG (BA42) and verbal intelligence quotient (IQ) were correlated significantly with the Wechsler Intelligence Scale for Children – Third Edition (WISC-III) (ß=−.57, p<.0001) and level of SES (ß=−.55, p<.0001). The present findings suggest that the development of the auditory association cortex involved in language processing is affected, causing insufficient pruning during brain development. We therefore assert that differences in the neuroanatomical substrate of pseudohypacusis subjects result from a developmental disorder in auditory processing

Anorexia Nervosa during Adolescence Is Associated with Decreased Gray Matter Volume in the Inferior Frontal Gyrus.

Anorexia nervosa (AN) is an eating disorder characterized by the relentless pursuit to lose weight, mostly through self-starvation, and a distorted body image. AN tends to begin during adolescence among women. However, the underlying neural mechanisms related to AN remain unclear. Using voxel-based morphometry based on magnetic resonance imaging scans, we investigated whether the presence of AN was associated with discernible changes in brain morphology. Participants were 20 un-medicated, right-handed patients with early-onset AN and 14 healthy control subjects. Group differences in gray matter volume (GMV) were assessed using high-resolution, T1-weighted, volumetric magnetic resonance imaging datasets (3T Trio scanner; Siemens AG) and analyzed after controlling for age and total GMV, which was decreased in the bilateral inferior frontal gyrus (IFG) (left IFG: FWE corrected, p < 0.05; right IFG: uncorrected, p < 0.05) of patients with AN. The GMV in the bilateral IFG correlated significantly with current age (left IFG: r = -.481, p < .05; right IFG: r = -.601, p < .01) and was limited to the AN group. We speculate that decreased IFG volume might lead to deficits in executive functioning or inhibitory control within neural reward systems. Precocious or unbalanced neurological trimming within this particular region might be an important factor for the pathogenesis of AN onset

Voxel based morphometry results.

<p>Locations displaying significant differences between AN and control participants in regional GMV. Significantly lower GM densities among AN participants were revealed in the bilateral IFG (Brodmann area 45/46). Color scale: 0–5 represents t-values.</p

Clinical variables assessed among anorexia and control participants.

<p>Abbreviations: S.D., standard deviation; df, degree of freedom; FSIQ, full scale intelligence quotient; BMI, body mass index;</p><p>Clinical variables assessed among anorexia and control participants.</p

Regional gray matter volume decreases in AN patients compared with the control group.

<p>Regional gray matter volume decreases in AN patients compared with the control group.</p

Further delineation of the phenotype of chromosome 14q13 deletions: (positional) involvement of FOXG1 appears the main determinant of phenotype severity, with no evidence for a holoprosencephaly locus

BackgroundDeletions including chromosome 14 band q13 have been linked to variable phenotypes. With current molecular methods the authors aim to elucidate a genotype-phenotype correlation by accurately determining the size and location of the deletions and the associated phenotype.MethodsHere the authors report the molecular karyotyping and phenotypic description of seven patients with overlapping deletions including chromosome 14q13.ResultsThe authors show that deletions including 14q13 result in a recognisable phenotype mainly due to haploinsufficiency of two genes (NKX2-1, PAX9). FOXG1 (on chromosome band 14q12) involvement seems to be the main determinant of phenotype severity. The patients in this study without FOXG1 involvement and deletions of up to 10 Mb have a relatively mild phenotype. The authors cannot explain why some patients in literature with overlapping but smaller deletions appear to have a more severe phenotype. A previously presumed association with holoprosencephaly could not be confirmed as none of the patients in this series had holoprosencephaly.ConclusionsFOXG1 appears the main determinant of the severity of phenotypes resulting from deletions including 14q13. The collected data show no evidence for a locus for holoprosencephaly in the 14q13 region, but a locus for agenesis of the corpus callosum cannot be excluded.status: publishe

MLL2

Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay, intellectual disability, specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids, prominent digit pads, and skeletal and visceral abnormalities. Mutations in MLL2 and KDM6A cause Kabuki syndrome. We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58) and/or targeted resequencing (n = 45) or whole exome sequencing (n = 5). We identified a mutation in MLL2 or KDM6A in 50 (61.7%) and 5 (6.2%) cases, respectively. Thirty‐five MLL2 mutations and two KDM6A mutations were novel. Non‐protein truncating‐type MLL2 mutations were mainly located around functional domains, while truncating‐type mutations were scattered through the entire coding region. The facial features of patients in the MLL2 truncating‐type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome; those of the other groups were less typical. High arched eyebrows, short fifth finger, and hypotonia in infancy were more frequent in the MLL2 mutation group than in the KDM6A mutation group. Short stature and postnatal growth retardation were observed in all individuals with KDM6A mutations, but in only half of the group with MLL2 mutations. © 2013 Wiley Periodicals, Inc