An increasing amount of genetic data supports our understanding of the mechanisms underlying the development of the human brain. In the last decade, we have more opportunities to consider what differentiates humans and apes. As next-generation sequencing is still improving the efficiency and accuracy of diagnosing rare disorders, genetic results often remind us of what we have missed in unclear phenotypes of patients. What are our roles, then, as child neurologists? How can we better contribute to the life of patients and families until new therapeutic options become available? This manuscript focuses on the historical aspect of molecular biology that evolved in conjunction with the development of medical genetics in the research field of autism spectrum disorder.

  Objective: In the event of a disaster, patients with muscular dystrophy and their families will face difficulties ensuring their own safety and living in a shelter. This study aimed to investigate the current status of these patients' disaster preparations. We first report the background of these patients. Methods: From 2014 to 2015, we distributed questionnaires about disaster preparation to members of the Japan Muscular Dystrophy Association. We conducted statistical analysis of the patients' background (who they lived with, age, sex, employment, need for assistance, use of medical instruments). Results: From the 876 questionnaires returned (53.8% response rate), we analyzed 776 responses from patients living in their own house. Of the selected respondents, the median age was 31 years (range, 1-83 years) ; 5.2% were under school age, 25.4% were students, and 20.7% were workers. The results showed that 85.3% of the patients needed some assistance, and 32.1% used respirators. Conclusions: It is necessary for patients using respirators to maintain an electrical supply in preparation for disasters. Although some money and work are needed for the preparation, the patients' background indicates that they need economic support and human assistance.

  Objective: We investigated the background of patients with muscular dystrophy and stated that they need economic support and human assistance to prepare for disasters in the first report. The purpose of this study was to investigate the current status of these patients' individual disaster preparations. Methods: From 2014 to 2015, we distributed questionnaires about disaster preparation to patients with muscular dystrophy who were members of the Japan Muscular Dystrophy Association. We analyzed the responses excluding their background. Results: From the 876 questionnaires returned (53.8% response rate), we analyzed 776 responses from patients living in their own house. The results showed that 34.4% had prepared for daily necessities for three days, 28.1% had prepared a copy of their health insurance card, 8.0% had prepared a Help Card, and 18.4% had an electrical supply in their houses. Based on additional comments, some respondents could not obtain information about disaster preparation and did not know how to prepare for a disaster ; meanwhile, preparations by the government were not suitable for their needs. Conclusions: Substantial improvements in disaster preparation are crucial for patients with muscular dystrophy : for example, arranging for an electrical supply and a Help Card. Furthermore, their background indicates that they need assistance with preparations and the associated costs. Government initiatives to improve economic support, human assistance, and provision of shelter for people with disabilities are required.

  Objective: For the afterschool day services guidelines revision, we investigated the changes in the quality of support after the guidelines formulation and the contents that should be added. Methods: In November 2018, questionnaire surveys were sent to 12,480 institutions providing afterschool day services in Japan. Responses were received through the mail, and some contents could be input on the internet directly. Results: Effective responses were received from 3,845 institutes with a response recovery of 30.8%. According to the type of institution, 59.8% and 40.2% were afterschool day services and multi-functional establishments, respectively. Of these, 201 institutions (5.2%) catered to the severely-disabled children. They were used by many developmentally disabled, intellectually disabled, and lower grade elementary school children. After implementing the guidelines, change was observed in 65.2% of establishments which led us to conclude that they were effective. For the revision, content from a developmental viewpoint ; characteristics of different of disabilities, especially of severely-disabled children ; and consistency with other guidelines should be taken into consideration. Conclusions: The guidelines for afterschool day services were implemented in many establishments, and there were some qualitative changes. For the revision, the content from a developmental viewpoint and character of disabilities would be inserted while maintaining consistency with other guidelines.

  SUCLA2-related mitochondrial DNA depletion syndrome is known as Leigh syndrome with methylmalonic aciduria. The patient was a 12-year-old girl with non-consanguineous parents. The clinical features included psychomotor retardation, hypotonia, sensorineural hearing impairment, feeding difficulty, growth retardation, muscular atrophy, external ophthalmoplegia, blepharoptosis, gastroesophageal reflux, recurrent vomiting, sagittal craniosynostosis, peripheral axonal neuropathy, restrictive respiratory failure and kyphoscoliosis. Lactate levels in blood and cerebrospinal fluid were elevated at 8 months of age, and brain MRI showed cerebral atrophy. The MRI at 2 years of age revealed hyperintense areas in the bilateral basal ganglia on T2-weighted imaging. Therefore, the patient was diagnosed with Leigh syndrome. Although the serum acylcarnitine profile revealed slightly elevated propionylcarnitine, urine organic acid analysis was decided as normal. At 9 years of age, exome sequencing for the research of peripheral neuropathy revealed novel compound heterozygous variants, NM_003850.2 (SUCLA2) : c.1300del (p.Asp434Metfs^＊8) ＋c.664-1G＞A. Her parents were heterozygous of each variant. A second analysis of urine organic acid showed mildly elevated methylmalonic acid. Muscle biopsy revealed that the activities of complexes Ⅰ and Ⅳ were at the lower limit of the normal range. Thus, the patient was diagnosed with SUCLA2-related mitochondrial DNA depletion syndrome. It is important to pay attention to elevated serum propionylcarnitine and mildly elevated urinary methylmalonic acid levels in patients with mitochondrial diseases.

  We describe cases of two girls (aged 55 and 49 months) with type Ⅱ and type Ⅲ spinal muscular atrophy (SMA) who obtained powerchairs at preschool age. The patients showed muscle hypotonia, loss of deep tendon reflexes, and finger fasciculations at disease onset. Deletions of exons 7 and 8 of the SMN1 gene were detected. Since both patients were unable to walk and had a disability certificate, they were entitled to receive a suitable mobility device under the social welfare system. The patients began practicing the use of a powerchair under the guidance of a physical therapist at 3 years of age. Subsequent applications for powerchairs were initially denied by the city offices due to their young age. The patients' attending pediatricians and caregivers directly negotiated with the office to emphasize the importance of powerchairs for independent mobility. Finally, after a practical investigation at the patients' homes and kindergartens, a powerchair was approved for each case. Although children with SMA cannot walk, they “can move” independently. Therefore, pediatricians “need to move” to support patients in obtaining suitable devices at an optimal time in their development.

  We identified a variant in the carboxyl terminal binding protein 1 gene, NM_001328.3 (CTBP1) : c.1024C＞T [p.R342W] , in a 14-year-old boy who had psychomotor regression and progressive cerebellar atrophy. The CTBP1 is a causative gene of hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (HADDTS ; #617915). This patient showed two characteristics compared with the findings in previously reported cases : 1) initial diagnosis of congenital fiber-type disproportion (CFTD) was made by muscle biopsy at his age of 4 years, and 2) there was no tooth enamel defect, which is one of the main symptoms of HADDTS. Because HADDTS is associated with various central nervous system diseases, CTBP1 should be considered as a possible candidate gene for patients showing a clinically progressive course of psychomotor regression and progressive cerebellar atrophy.

  We report a case of Landau-Kleffner syndrome (LKS) with improvement of cognitive outcome after regular methylprednisolone pulse (MP) therapy. The patient manifested focal motor seizures, and atypical absence seizures followed by auditory agnosia at 6 years of age, and was diagnosed with LKS at age 8. MP therapy was started because of aggravation of auditory agnosia, onset of psychiatric symptoms, and increased frequency of atypical absence seizures. With regular MP therapy, the symptoms improved, and MP therapy was tapered and discontinued at 10 years of age. Cognitive function has remained normal even after discontinuation of all treatment at age 18.