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Background There are few studies on hiragana reading skill and phonological awareness in Japanese schoolchildren with periventricular leukomalacia (PVL). Methods Three seven-year-old children with PVL who had no intellectual disabilities or dysarthria were recruited. Their perinatal information, brain magnetic resonance image (MRI) at term equivalent age, accompanying neurodevelopmental disorders, ophthalmologic features, Kaufman Assessment Battery for Children (K-ABC), a hiragana reading test (four tasks), and a phonological awareness task (mora reversal tasks) were analyzed. Results Patient (Pt) 1 and pt2 were male. Pt2 and pt3 were siblings of triplets. Their gestational age was 28 or 32 weeks, and their birth weights were 1196, 1554, and 1848 g, respectively. Their brain MRI revealed cystic or non-cystic periventricular white matter injury involving the deep white matter at the trigone of both lateral ventricles. Pt1 had attention-deficit/hyperactivity disorder and pt3 had pervasive developmental disorder not otherwise specified. All patients had strabismus with spared best-corrected visual acuity. Scores of Reading/Decoding in K-ABC ranged from 89 to 99. As for the single mora reading task or the non-word reading task in the kana reading test, Z scores of their reading time ranged from 2.3 to 5.9 compared to control children. Pt1 and pt3 made significant errors in the mora reversal task of three-mora words, whereas all patients could answer all words correctly in the mora reversal task of two-mora words. Conclusion All children showed significantly prolonged reading time despite their adequate letter recognition. Two patients showed delayed phonological awareness. It was suggested that hiragana decoding impairment due to subcortical and/or cortical injury related to PVL affected their reading ability.

Background The characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations (KABUK1) have not yet been well documented. This is the first review to explore this. Materials & methods We enrolled 14 patients with KABUK1, whose median age was 13.6 years (range = 4.1–21.3 years). Their medical records from October 1981 to May 2016 were retrospectively analyzed. Results Epilepsy was present in 5 (36%) patients. Four of these patients presented with nonsense mutations and one with missense mutations. None presented with brain abnormalities. Four patients presented with annual or monthly focal seizures, of which three evolved to bilateral convulsive seizures. Median onset age of focal epilepsy was 11.8 years (range = 9.5–12.8 years). One presented with monthly myoclonic seizures from age 11.2, whose mother with no other KABUK1 features, had focal epilepsy. The cumulative incidence of epilepsy related to KABUK1 up until age 13 was 45%. Interictal electroencephalogram revealed focal paroxysmal epileptiform discharges (in frontal, central, and parietal regions) in three patients, diffuse high-voltage spike-and-waves in one patient, and normal sleep record in one patient. Myoclonic seizures were rapidly controlled by levetiracetam. In contrast, focal seizures were not controlled in the early period of antiepileptic therapy. Conclusion This long-term follow-up of patients with KABUK1 revealed a higher prevalence of epilepsy than previously reported. The age of epilepsy onset and rate of focal seizures evolving to bilateral convulsive seizures in KABUK1 were also higher than previously reported in patients with clinically diagnosed Kabuki syndrome. Although seizure outcome is reported to be favorable in Kabuki syndrome, focal seizures in patients with KABUK1 were not immediately responsive to medication.

Arts syndrome is characterized by early-onset hypotonia, ataxia, intellectual disability, sensorineural hearing impairment, progressive optic atrophy, and a tendency to develop infections. Arts syndrome is an X-linked disorder caused by a loss-of-function mutation in the PRPS1 gene, which encodes phosphoribosylpyrophosphate synthetase 1. Only three families have been reported. Here, we report another family with Arts syndrome. The initial symptoms of the 1-year-old proband were hypotonia and ataxia, worsening recurrent infection-triggered muscle weakness, motor and intellectual developmental delay, and hearing loss. Both central nervous system involvement and peripheral neuropathy were demonstrated. His three maternal uncles had died before the age of 3years. A genetic analysis of PRPS1 revealed a novel missense mutation, c.367C>G (p.His123Asp). PRPS enzymatic activity was markedly reduced in the patient. His mother was supposed to be an asymptomatic carrier. Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance.

Purpose Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy. Methods A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20 years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)). Results The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration. Conclusion LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range.