Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the 'molar tooth sign'. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole-exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24 + 6) families (83.3%). We identified eight mutated genes in 27 (21 + 6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012-12T>A (75.0%), an allele that has not been reported in non-Japanese populations. Therefore c.6012-12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet-Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.

SummaryPurpose: Ictal magenetoencephalographic (MEG) discharges convey significant information about ictal onset and propagation, but there is no established method for analyzing ictal MEG. This study sought to clarify the usefulness of time-frequency analyses using short-time Fourier transform (STFT) for ictal onset and propagation of ictal MEG activity in patients with neocortical epilepsy.Methods: Four ictal MEG discharges in two patients with perirolandic epilepsy and one with frontal lobe epilepsy (FLE) were evaluated by time-frequency analyses using STFT.Prominent oscillation bands were collected manually and the magnitudes of those specific bands were superimposed on individual 3D-magnetic resonance images.Results: STFT showed specific rhythmic activities from alpha to beta bands at the magnetological onset in all four ictal MEG records. Those activities were located at the vicinity of interictal spike sources, as estimated by the single dipole method (SDM), and two of the four ictal rhythmic activities promptly propagated to ipsilateral or bilateral cerebral cortices. The patients with FLE and perirolandic epilepsy underwent frontal lobectomy and resection of primary motor area respectively including the origin of high-magnitude areas of a specific band indicated by STFT, and have been seizure free after the surgery.Conclusions: STFT for ictal MEG discharges readily demonstrated the ictal onset and propagation. These data were important for decisions on surgical procedure and extent of resection. Ictal MEG analyses using STFT could provide a powerful tool for noninvasive evaluation of ictal onset zone.

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Background: Motor coordination problems (MCP) in children can sometimes be diagnosed as developmental coordination disorder. Early intervention for developmental coordination disorder is necessary because it often continues into adolescence, causing mental and physical complications. Few studies have investigated the prevalence of childhood MCP in the Japanese population, examining the risk factors for MCP. We therefore investigated the prenatal factors associated with MCP in preschool-age children. Methods: This study was based on a prospective cohort study, the Hokkaido Study on Environment and Children's Health. Mothers of 4,851 children who reached the age of 5 years within the study-period received questionnaires, including the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ-J). We examined the risk factors associated with MCP using logistic regression analysis. Results: Of 3,402 returned DCDQ-J questionnaires, 3,369 were answered completely. From the 3,369 children, we categorized having MCP by using two cutoff scores: that of the DCDQ'07 and the cutoff at the 5th percentile of a total DCDQ-J score. Comparing children with and without MCP, we found significant differences in the education level of the mothers, annual household income during pregnancy, maternal alcohol consumption and smoking during pregnancy, and sex and age of the children at the time of completing the DCDQ-J by both categorizations. Adjusted logistic regression analysis revealed that maternal smoking during the first trimester of pregnancy and male sex were significantly associated with MCP. Conclusions: Our results suggest that maternal smoking during pregnancy is the main factor associated with MCP in preschool-age children.

SUMMARYA dysplastic neuronal lesion of the floor of the fourth ventricle (DNFFV) causes hemifacial seizures (HFS) from early infancy. However, it is still controversial whether HFS is generated by the facial nerve nucleus or cerebellar cortex. In this study, we confirm a direct correlation between the rhythmic activities in the DNFFV and HFS using intraoperative electroencephalography (EEG) and electromyography (EMG) monitoring. Our results support the theory that a DNFFV provokes ipsilateral HFS via the facial nerve nucleus. KEY WORDS: Facial nerve nucleus, Hemifacial seizure, Dysplastic neuronal lesion, Floor of the fourth ventricle.There are several reports of hemifacial seizures (HFS) caused by dysplastic neuronal lesions of the floor of the fourth ventricle (DNFFV). Delalande et al. (2001) described theta or beta rhythmic activity in the DNFFV using a depth electrode inserted during surgery. However, there have been no reports elucidating a direct correlation between DNFFV and HFS or explaining the possible pathophysiology of a relationship between DNFFV and HFS. In this study, we sought to assess the pathophysiology of DNFFV and HFS by real-time monitoring of HFS during surgery. Case ReportThe patient was a 20-month-old boy who was born without perinatal problems. However, he had seizures with motion arrest and right eyelid contraction soon after birth. At 3 months of age, brain magnetic resonance imaging (MRI) demonstrated a mass lesion on the right side of the floor of the fourth ventricle, which showed isointensity to gray matter in both the T 1 -and T 2 -weighted images and was not enhanced by gadolinium injection. From 4 months of age, his seizures changed to intermittent closure of the right eye and right perioral contraction. Although the patient's psychomotor development was normal in infancy, he could not walk alone at 20 months. His seizures increased gradually and by 20 months of age were occurring every day at almost 20-s intervals while he was both awake and asleep.He underwent tumor resection at 20 months of age. An MRI study obtained for preoperative evaluation revealed a mass lesion the same as at 3 months of age (Fig. 1A). Written informed consent was obtained for intraoperative monitoring before the operation. Needle electrodes were inserted into the right upper and lower eyelids and the right orbicular muscle of the mouth to detect the hemifacial seizures during surgery. A muscle relaxant was not used. Sheet electrodes with 20 contacts were used for evaluating cerebellar cortices, and a strip electrode with four contacts was used within the fourth ventricle.During the surgery, although the sheet electrodes on the bilateral cerebellar cortices did not show any ictal findings related with eyelid twitching, the strip electrode on the tumor demonstrated rhythmic theta waves during eyelid twitching corresponding to electromyography (EMG) (Fig. 1B,C). At the moment of biopsy resection, aberrant EMG occurred with wild eyelid twitching, and then the patient's seizure disappeared soon after appro...

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