A functional analysis of GABARAP on 17p13.1 by knockdown zebrafish.

Array-based comparative genomic hybridization identified a 2.3-Mb microdeletion of 17p13.2p13.1 in a boy presenting with moderate mental retardation, intractable epilepsy and dysmorphic features. This deletion region was overlapped with the previously proposed shortest region overlapped for microdeletion of 17p13.1 in patients with mental retardation, microcephaly, microretrognathia and abnormal magnetic resonance imaging (MRI) findings of cerebral white matter, in which at least 17 known genes are included. Among them, DLG4/PSD95, GPS2, GABARAP and KCTD11 have a function in neuronal development. Because of the functional importance, we paid attention to DLG4/PSD95 and GABARAP, and analyzed zebrafish in which the zebrafish homolog of human DLG4/PSD95 and GABARAP was knocked down and found that gabarap knockdown resulted in small head and hypoplastic mandible. This finding would be similar to the common findings of the patients with 17p13.1 deletions. Although there were no pathogenic mutations in DLG4/PSD95 or GABARAP in a cohort study with 142 patients with idiopathic developmental delay with/without epilepsy, further studies would be required for genes included in this region.

Developmental changes in attention to social information from childhood to adolescence in autism spectrum disorders: a comparative study.

BACKGROUND: Elucidating developmental changes in the symptoms of autism spectrum disorder (ASD) is important to support individuals with ASD. However, no report has clarified the developmental changes in attention to social information for a broad age range. The aim of this study was to investigate the developmental changes in attention to social information from early childhood to adolescence in individuals with ASD and typically developed (TD) children. METHODS: We recruited children with ASD (n = 83) and TD participants (n = 307) between 2 and 18 years of age. Using the all-in-one-eye-tracking system, Gazefinder, we measured the percentage fixation time allocated to areas of interest (AoIs) depicted in movies (the eyes and mouth in movies of a human face with/without mouth motion, upright and inverted biological motion in movies showing these stimuli simultaneously, people and geometry in preference paradigm movies showing these stimuli simultaneously, and objects with/without finger-pointing in a movie showing a woman pointing toward an object). We conducted a three-way analysis of variance, 2 (diagnosis: ASD and TD) by 2 (sex: male and female) by 3 (age group: 0-5, 6-11, and 12-18 years) and locally weighted the scatterplot smoothing (LOESS) regression curve on each AoI. RESULTS: In the face stimuli, the percentage fixation time to the eye region for the TD group increased with age, whereas the one for the ASD group did not. In the ASD group, the LOESS curves of the gaze ratios at the eye region increased up to approximately 10 years of age and thereafter tended to decrease. For the percentage fixation time to the people region in the preference paradigm, the ASD group gazed more briefly at people than did the TD group. LIMITATIONS: It is possible that due to the cross-sectional design, the degree of severity and of social interest might have differed according to the subjects' age. CONCLUSIONS: There may be qualitative differences in abnormal eye contact in ASD between individuals in early childhood and those older than 10 years.

Mental retardation, spasticity, basal ganglia calcification, cerebral white matter lesions, multiple endocrine defects, telangiectasia and atrophic skin: a new syndrome?

We report on an 8-year-old boy with mental retardation and spastic tetraparesis associated with atrophic skin on the face and extremities, telangiectasia, and severe dental caries. Basal ganglia calcification and multiple lesions in the subcortical white matter have been present since infancy. The patient has complications of liver dysfunction, multiple endocrine defects, and elevation of blood/cerebrospinal fluid lactate. Extensive laboratory examinations, including skin and muscle biopsies, and UV- and mitomycin C-sensitivity tests on fibroblasts, provided no evidence of a specific disease entity. No deterioration was noted, and supplementation of riboflavin and other vitamins had no apparent effect on the neurodevelopmental status of this patient. This patient may represent a novel disease entity, with unclear pathogenesis.

Congenital ocular motor apraxia: clinical and neuroradiological findings, and long-term intellectual prognosis.

The severity of intellectual sequelae and prognosis varies in patients with congenital ocular motor apraxia (COMA). Here, we explored this phenomenon with regard to the accompanying oculomotor signs and gross motor development, as well as the subtentorial structure defects. Ten patients diagnosed with COMA (M:F=4:6, 4-37 years old) were reviewed. Four individuals who gained the ability to walk at 2 years or earlier showed normal intellect and social skills. Those who walked later often showed accompanying intellectual (5/6) and speech (6/6) disabilities. In this latter group, atypical oculomotor signs for COMA (presence of nystagmus, mild limitation of vertical gaze, slower head thrust, and marked improvement of lateral saccade during early childhood) were often noted (4/6). Minor anomalies of fingers and toes were also common in this group. Neuroimaging was conduced in nine patients (pneumoencepharography 1; computed tomography: 8, magnetic resonance imaging: 2). Dilatation of the fourth ventricle, mainly at the level of the midbrain or upper pons (n=7), and hypoplastic cerebellar vermis (n=6) were commonly observed in both the early- and late-walking groups. 'Molar tooth' signs (n=3) were exclusively noted in the late-walking group, and often accompanied by atypical oculomotor signs (3/3) and intellectual disabilities (2/3). Vermian hypoplasia and dilatation of the fourth ventricle at the upper brainstem level in COMA patients, with or without intellectual disabilities, suggested that the cardinal lesion for OMA may exist in these areas. The presence of a subset of 'atypical' COMA patients may suggest that COMA with subtle infratentorial abnormality represents a heterogeneous disease category, showing similar oculomotor disturbance. This review indicated that clinical and neuroradiological inspection might be valuable for prediction of long-term intellectual prognosis in COMA patients.

Forced mouth opening reaction: a primitive reflex released from cortical inhibition.

We report the case of a 6-year-old girl with congenital adrenal hyperplasia, who showed 'forced mouth opening reaction' during the course of acute encephalopathy due to adrenal crisis. When an object was moved towards her mouth, or when the corner of her mouth was stroked with a tongue depressor, she would immediately open her mouth fully and hold it open. This reaction appeared transiently during the course of her illness in association with other frontal release signs including the rooting, groping and palmomental reflexes. Magnetic resonance imaging showed bilateral widespread lesions involving the gray and white matters in the frontal lobes, and less severe lesions in the temporal and parietal areas. We propose that this unique reaction is a sign of a release phenomenon, and represents the emergence of primitive reflexes in the absence of cortical inhibition in some types of encephalopathies.

[Influenza-associated encephalopathy with onset of prolonged convulsion: a case report].

A 1-year-old girl with influenza-associated encephalopathy initially exhibited prolonged febrile convulsions and subsequent drowsiness. She became unconsciousness and experienced a cluster of seizures 4 days later. Diffusion-weighted magnetic resonance imaging (DWI) showed high signal intensity in the bilateral frontal white matter. This signal change migrated to the bifrontal cortical areas and the caudate nuclei within 10 days, when T2 elongation appeared over the gray and white matter of frontal lobes. Choreoathetosis and oculogyric crisis were transiently noted at this period. Frontal lobe signs, including the forded mouth opening response, after diminution of these movement disorders. The DWI signal change subsequently resolved and frontal cortical atrophy appeared thereafter. Levels of inflammatory cytokines in the cerebrospinal fluid were normal during the acute phase of clinical course. The biphasic clinical course with initial prolonged seizure, involvement of the frontal lobes, and the progression of signal change on DWI from white to gray matter, meets the characteristics of "status epilepticus-type acute encephalopathy" suggested by Shiomi et al. Although pentobarbital infusion, steroid pulse therapy and mild hypothermia did not show any apparent effects on the clinical course of this patient, further trial of these therapies may be warranted for the treatment of this type of encephalopathy.