Yushiro Yamashita

Guidelines for reporting clinical features in cases with MECP2 mutations

An international group recommends that papers relating phenotypes to genotypes involving mutations in the X chromosome gene MECP2 should provide a minimum data set reporting the range of disturbances frequently encountered in Rett Syndrome. A simple scoring system is suggested which will facilitate comparison among the various clinical profiles. Features are described which should prompt screening for MECP2 mutations.

Scale properties of the Japanese version of the Strengths and Difficulties Questionnaire (SDQ): A study of infant and school children in community samples

The Strengths and Difficulties Questionnaire (SDQ) is a short screening instrument which addresses the positive and negative behavioral attributes of infants, children and adolescents. The SDQ is widely used to evaluate child developmental disabilities, psychological and psychiatric conditions or disorders in Japan. However, we did not have normative data for the Japanese version until now. To establish the community-based data and properties for the Japanese version, we collected and evaluated parent ratings of a total of 2899 Japanese children aged 4-12 years, including 1463 boys and 1436 girls. Statistical evaluation of psychometric properties included a factor analysis verifying the proposed scale structure, an assessment of scale homogeneities, and the determination of age, gender and relationship of each difficulties scale, or prosocial scale. The total difficulties score in boys (8.70 +/- 5.03) was higher than in girls (7.86 +/- 4.88). Based on the distributions of SDQ scores observed in the Japanese community sample, recommended bandings identifying normal, borderline, and abnormal (clinical ranges) were defined for each scale, and some gender difference was found in some difficulties and prosocial SDQ scores. After evaluating parent ratings obtained in a community-based sample, the Japanese SDQ was shown to possess favorable psychometric properties. Thus, the Japanese translation of this popular and versatile instrument seems to be approximately as reliable and useful as the original English questionnaire.

Patients with the R133C mutation: is their phenotype different from patients with Rett syndrome with other mutations?

Rett syndrome is an X linked dominant neurodevelopmental disorder with an incidence of 1:10 000 females in Australia.1 It is characterised by apparently normal development between 6 and 18 months, followed by a period of regression with loss of purposeful hand use, deceleration of head growth, and onset of repetitive, stereotypic hand movements.2 Affected people also manifest gait ataxia and apraxia, autistic features, epileptic seizures, respiratory dysfunction, autonomic dysfunction, and decreased somatic growth.2,3 In recent years it has become apparent that the phenotypic range of this disorder is much wider than previously thought. Some patients may have a milder phenotype and retain the ability to walk or speak and others have an earlier onset and more severe features. People who have some but not all of the necessary criteria have been categorised as atypical4 or as one of six variant forms.5 Rett syndrome has now been shown to be associated with mutations in the methyl-CpG-binding protein 2 (MeCP2).6 For many genetic disorders, the next stage in research after the identification of the gene involves describing the relation between genotype and phenotype, and the phenotypic diversity produced by different mutations in the same gene. Some research has found that people with missense MECP2 mutations may have a milder phenotype than those with truncating mutations.7,8 Weaving et al 9 found that age at onset of hand stereotypies was later and speech and height (but not head growth) were slightly more normal in those with missense mutations whereas Nielsen et al 10 found no difference in severity between these mutation types. In the study of Amir et al 11 breathing abnormalities were found to be more common with truncating mutations and scoliosis more common with missense mutations. Hoffbuhr et al 12 concluded that patients …

Acute disseminated encephalomyelitis after Japanese B encephalitis vaccination

A 6-year-old girl (Patient 1) and a 5-year-old boy (Patient 2) with acute disseminated encephalomyelitis after Japanese B encephalitis vaccination are reported. Drowsiness, paresthesias, and gait disturbance were observed at 14 days (Patient 1) and 17 days (Patient 2) after the vaccination; however, transient impairment of visual acuity was only found in Patient 1. Laboratory examinations revealed slow theta waves on electroencephalography and elevated myelin basic protein in the cerebrospinal fluid in both patients. The most striking feature on magnetic resonance imaging was the combination of white matter lesions and abnormal intensity signals of the thalamus. The administration of oral prednisolone (2 mg/kg/day) markedly improved the clinical findings and abnormal magnetic resonance imaging findings. A similar magnetic resonance imaging finding of abnormal intensity of the thalamus with deep white matter lesions has been reported in patients with Japanese B encephalitis; therefore, thalamic lesions may be related to the naturally occurring encephalitis.

Prefrontal cerebral blood volume patterns while playing video games : A near-infrared spectroscopy study

Video game playing is an attractive form of entertainment among school-age children. Although this activity reportedly has many adverse effects on child development, these effects remain controversial. To investigate the effect of video game playing on regional cerebral blood volume, we measured cerebral hemoglobin concentrations using near-infrared spectroscopy in 12 normal volunteers consisting of six children and six adults. A Hitachi Optical Topography system was used to measure hemoglobin changes. For all subjects, the video game Donkey Kong was played on a Game Boy device. After spectroscopic probes were positioned on the scalp near the target brain regions, the participants were asked to play the game for nine periods of 15s each, with 15-s rest intervals between these task periods. Significant increases in bilateral prefrontal total-hemoglobin concentrations were observed in four of the adults during video game playing. On the other hand, significant decreases in bilateral prefrontal total-hemoglobin concentrations were seen in two of the children. A significant positive correlation between mean oxy-hemoglobin changes in the prefrontal region and those in the bilateral motor cortex area was seen in adults. Playing video games gave rise to dynamic changes in cerebral blood volume in both age groups, while the difference in the prefrontal oxygenation patterns suggested an age-dependent utilization of different neural circuits during video game tasks.

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome : pathological mutations and polymorphisms

A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.

The test of variables of attention (TOVA) is useful in the diagnosis of Japanese male children with attention deficit hyperactivity disorder

The purpose of this study was to evaluate the ability of the test of variables of attention (TOVA) to distinguish between 6- to 12-year-old Japanese male children with attention deficit hyperactivity disorder (ADHD group; n=17) meeting DSM-IV and ICD-10 criteria, and age-matched, normal Japanese male controls (control group; n=19). The TOVA is a computer-administered, visual continuous performance test that provides measures of attention. The ADHD group had significantly higher means than the control group in all variables: omission errors, commission errors, response time, response time variability, anticipatory responses, and multiple response. Control children exhibited age-related changes in two variables: response time and response-time variability, but no age-related changes were observed in any variables in the ADHD group. This preliminary study indicates that the TOVA makes a useful contribution to the diagnosis of Japanese male children with ADHD.

Multicenter study of paroxysmal dyskinesias in Japan—Clinical and pedigree analysis

To investigate the clinical features of paroxysmal dyskinesias and carry out a pedigree analysis, we conducted a multicenter survey in Japan. A questionnaire was mailed to 229 medical institutions. A total of 150 patients with paroxysmal kinesigenic choreoathetosis (PKC), including 53 sporadic cases and 97 affected individuals from 32 pedigrees, were identified. The mean age of onset of PKC was 8.8 years, and 80% of the cases were men. Of the 32 pedigrees with familial occurrence, 18 (56%) were compatible with an autosomal‐dominant inheritance (AD) with complete penetrance, and seven (22%) had AD with incomplete penetrance; the remaining seven were sibling recurrence cases with apparently healthy parents. In six of seven familial cases with incomplete penetrance, the disease gene was thought to be transmitted by clinically unaffected females. Paroxysmal dystonic choreoathetosis (PDC) was found in five cases, including two sporadic cases and three affected individuals from two pedigrees; the mean age of onset was 0.6 years, and a male predominance was noted (male:female = 4:1). There was one case of paroxysmal hypnogenic dyskinesia and one case of paroxysmal exertion‐induced dyskinesia. There is an unexplained male predominance for paroxysmal dyskinesias. When the genetic defect of patients with paroxysmal dyskinesias is identified, the pathophysiology of the disease will become more clear.

Photosensitive Seizures Provoked While Viewing “Pocket Monsters,” a Made-for-Televison Animation Program in Japan

Summary: Purpose: To describe the recent epidemic of photosensitive seizure that occurred in relation to an episode of the television animation program “Pocket Monsters,” we report four patients who experienced seizures while watching the episode in question. We also report some technical aspects of the program episode.

Increased urine phenylethylamine after methylphenidate treatment in children with ADHD

The urine levels of β‐phenylethylamine, 3‐methoxy‐4‐hydroxyphenyl glycol, homovanillic acid, and 5‐hydroxyindoleacetic acid were measured to clarify the neurochemical mechanism in attention deficit hyperactivity disorder. β‐Phenylethylamine levels were significantly lower in attention deficit hyperactivity disorder individuals (n = 37) than in controls (n = 21). The 22 children with attention deficit hyperactivity disorder were treated with methylphenidate, and they were further divided into methylphenidate responders (n = 18) and nonresponders (n = 4). β‐Phenylethylamine levels significantly increased after methylphenidate therapy in responders, whereas they did not increase in nonresponders.