Comprehensive gene analysis using next-generation sequencing has revealed many disease-related genes. As a result, the purpose of using comprehensive gene analysis has been expanding from the research level to the application to clinical diagnosis. In the analysis using next-generation sequencing, samples are prepared at the laboratory level, processed by a sequencer, and the analysis results are automatically obtained as a digital file. It is difficult to reach disease-related variants unless filtering and curation by expert physicians. In the process, it is necessary to recognize the meaning of variants, how to handle frequency information, how to use various databases, and the importance of trio analysis. Here, it is described how filtering and curation should be done, and how to make decisions in accordance with the ACMG guidelines.

  Objective: Screening for visual dysfunctions is now widespread thanks to the proven benefits of examination for early detection and treatment of ophthalmic diseases. Many children with developmental disorders often experience difficulty taking a vision test. Although the number of institutions using the Spot^TM Vision Screener (SVS) is increasing, there are as yet few reports of its use in people with disability. We therefore assessed the adaptability and utility of the SVS for testing people with disability in the outpatient department. Methods: The present retrospective study was based on a review of clinical information in patients’ medical records of our outpatient department. Patients who received an SVS test between October 2017 and September 2018 were enrolled. Descriptive statics is used to investigate clinical features, test results and ophthalmologic treatment. Results: In total, 134 patients tried to take the SVS test. Initially, 15 patients were unable to be evaluated. Some of these were later tested again, and in total, 129 patients were successfully evaluated. In the study cohort, 30 patients had autism spectrum disorder, 28 had attention deficit hyperactivity disorder, and 35 had an intellectual disability. According to the original reference values of the SVS test, 81 eyes of 48 patients had an abnormality. Among them, 24 eyes of 18 patients showed an abnormality according to the reference values established by the authors. Following the test, eight patients began using eyeglasses for the first time ; four of these demonstrated an improved visual response and were able to give their full attention to tasks. Conclusions: The majority of people with disability were successfully evaluated in the present study. Moreover, early vision detection of ametropia and strabometry can lead to their early treatment before they cause further developmental delay.

  Objective: We examined the therapeutic effects of nusinersen in patients with spinal muscular atrophy (SMA). Methods: We retrospectively evaluated motor function scale scores as an objective index and questionnaire responses from patients’ families as a subjective index. Motor function was assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders for SMA types I and II in those who could not achieve sitting, Hammersmith Functional Motor Scale Expand for SMA types II who could achieve sitting and III. Results: Eleven patients were included. Six patients had SMA type I, three patients had type II, and two patients had type III. The age when the first dose of drugs was administered ranged from 4 to 12 years. The baseline motor function scale score was 0 or 1 point (s) in patients with SMA type I, and the scores did not change after treatment. In patients with SMA type II/III, the scores increased except for in one case. In the questionnaire, most of the parents reported various effects : not only improvement of motor function, but also respiratory and gastrointestinal functions. We compared the pre- and post-treatment changes using the motor function scales, and data on treatment satisfaction were acquired from the questionnaires. There were four patients with no improvement but high satisfaction, and two patients with improvement but low satisfaction. Conclusions: Patients and their families experience a variety of subjective effects. In some cases, parents reported small changes that were not captured by the motor function scales, and in other cases, the evaluation of motor function scale scores and impression about motor function from their families were not correlated. If the evaluation with a single index is insufficient, it is necessary to evaluate the therapeutic effect from multiple angles.

  Objective: There are no guidelines on the end of life care for patients with Duchenne muscular dystrophy (DMD) in Japan. We describe our experience of advance care planning (ACP) in three patients with DMD. Methods: We conducted conversations with DMD patients and their families according to the ACP steps provided by the Ministry of Health, Labour and Welfare and the four quadrant-approach to clinical ethics, using a multidisciplinary team approach. Results: Patient 1 was a 22-year-old male to whom it was important to continue spending his daily life as he currently did. He desired palliative care and to die naturally. Patient 2 was a 23-year-old male who wanted the freedom to do whatever he chose. He too desired palliative care and to die naturally. During the ACP, he developed nonsustained ventricular tachycardia, for which he decided to undergo cardioverter defibrillator implantation. Patient 3 was a 22-year-old male to whom it was important to face himself. He learned to accept his DMD with ACP support, and opted to receive noninvasive positive pressure ventilation. He ultimately decided that he wanted to receive palliative care and die naturally. All the family members agreed with their sons’ choices. Our multidisciplinary team also respected the decisions of the patients and their families. Conclusions: ACP in cooperation with a multidisciplinary team enabled us to understand the will and decision by DMD patients and their families at the end of life.

  Klüver-Bucy syndrome (KBS) is a neurobehavioral syndrome that exhibits distinctive symptoms including psychic blindness, visual agnosia, hyperorality, altered emotional status, and hypersexuality due to temporal lobe disorder. We report a 5-year-old boy with symptoms of KBS after a minor head trauma. Oral tendencies, visual unresponsiveness, agnosia, emotional change, and memory disturbance were observed after head bruise due to falling. Although no obvious lesions were apparent on the brain MRI, the EEG showed slow waves that were left temporal dominant. ^99mTc-ECD single photon emission computer tomography (SPECT) also revealed hypoperfusion of cerebral blood flow in the bilateral cerebellum, right temporo-parietal lobe, thalamus and basal ganglia. After various treatments for encephalopathy, on the 28th day of the disease, the symptoms resolved and the abnormalities on EEG also disappeared. In children, there are many reports of KBS developing after encephalopathy and encephalitis. However, few cases of onset accompanying head trauma have been reported. Even with encephalopathy after head injury in children, it is necessary to pay attention to KBS. Also, even when there is no obvious abnormal finding on a brain MRI, SPECT and EEG might be useful for the detection of the damage site.

  We report a 5-year-old girl with no apparent perinatal abnormalities, except for right ptosis. The patient was admitted to our department at 2 years of age, as she was unable to walk without assistance despite 6 months of physical therapy. Continued right ptosis, right eye exotropia, high arched palate, and asymmetrical nasolabial sulcus were observed. Although mental retardation was absent and the patient could thus understand instructions, she was unable to walk up the stairs one step at a time, jump or one-step stand at age 3. At that time, we noticed that her muscle weakness was right dominant. Her serum creatine kinase level was normal, muscle CT revealed right greater gluteal muscle atrophy, and T1 weighted MRI demonstrated high intensity areas in the bilateral soleus muscles. At age 5, parental consent was obtained, and a muscle biopsy of the biceps brachii was performed. Centronuclear myopathy was detected by histopathological examination, and genetic testing revealed a previously reported heterozygous MTM1 missense mutation (NM_000252.3 (MTM1) : c.721C>T [p.Arg241Cys]). Reported characteristics of affected female carriers with this mutation include delayed onset of walking, asymmetric lateral appearances, ptosis, extraocular muscular disorder, and asymptomatic muscular weakness. Since there are no reports of this mutation in Japan, we describe this case in an effort to increase awareness of this disease when diagnosing asymmetric muscle weakness.

  Myelin oligodendrocyte glycoprotein antibody (MOG-Ab) is identified in some patients with ADEM. Whether serial change of MOG-Ab titer is useful for deciding on the therapeutic strategy for multiphasic ADEM has not been clarified. We report the case of multiphasic ADEM who was treated with intravenous immunoglobulin (IVIG) therapy and whose MOG-Ab was serially evaluated. The patient is 9-year-old boy. He showed acute onset of headache and delirium. T2-weighted and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) showed multiple hyperintense lesions in bilateral subcortical and cortical areas, and we diagnosed the patient with ADEM. Although symptoms and MRI lesions were resolved by steroid pulse therapy, he experienced three time relapses characterized by headache and abnormal behavior as well as new MRI lesions during tapering of the therapy. We started monthly IVIG from 5 months after onset, and no relapse of ADEM was encountered. MOG-Ab titer ranged from 4,096 to 2,048 before IVIG therapy. After starting IVIG, MOG-Ab titer gradually decreased. We were able to decrease and discontinue oral steroids. After steroid discontinuation, MOG-Ab titer remained low. We started to decrease the dose of IVIG at 1 year and 3 months after the onset of ADEM and terminated IVIG at 1 year and 9 months after onset by checking low titer of MOG-Ab. Our results suggest that serial evaluations of MOG-Ab may contribute to the monitoring of disease activity and decision-making on drug tapering and termination for multiphasic ADEM. The utility of serial evaluations should be validated in studies of larger numbers of patients.

  The promotion of child home support is an issue to be addressed for pediatric care in Japan. By setting the hospitalization period from one to two weeks and repeating the hospitalization at intervals of approximately one to three months, according to the wishes of the family, child home support progresses in stages with parents coordinating hospitalization with special function hospitals. The results of the parent questionnaire, which we administered, showed that parents were satisfied with the center’s policy.

  We examined four patients who had difficulty in managing lower urinary tract dysfunction associated with a neurological disease and underwent cutaneous vesicostomy. The recurrent urinary tract infection disappeared in all the patients, and the hydronephrosis observed in two patients improved. Elimination of the need for medical intervention―clean intermittent catheterization―improved the quality of life of patients and families. Although cutaneous vesicostomy is a urinary diversion that results in urinary incontinence, it has several advantages in cases wherein conservative management is difficult and is a valuable tool that must be considered.