Pub Date : 2025-07-14DOI: 10.1016/j.bdcasr.2025.100096
Yanhong Zhu , Xu Cao , Hui Yan , Yanping Fan , Weidong Zhao , Yujun Zhan , Hongli Zeng , Chaoyang Zhou , Zhenjie Chen , Li Yu , Jianguo Cao
Background: ZNF526 has been recently identified as a gene associated with Dentici-Novelli neurodevelopmental syndrome (DENNED), an autosomal recessive disorder characterized by global developmental delay, microcephaly, cataracts, and epilepsy. It very rarely happens in the East Asian population with only 3 cases currently.
Case presentation: In this case report, we present two sibling patients from China with a novel compound heterozygous variant (c.1512_1513del and c.1501C>A) in the ZNF526 gene (NM_133444.3), expanding the phenotypic and geographic spectrum of DENNED. One patient's cranial MRI revealed widening of the extracerebral space in the bilateral frontotemporal region, abnormal EEG patterns, slow awake background activity, poor sleep background, and indistinguishable sleep cycles, which was never reported before. Our report also marks the first documentation of DENNED with this new ZNF526 heterozygous variant around the world.
Discussion: With our case, we discuss all published 9 cases of ZNF526 variants so far to enhance understanding of this rare disease and its clinical manifestations. We find that the reported DENNED in East Asia has some differences to cases in Europe and Middle East and there are some correlations between genetic variants and clinical manifestations.
{"title":"Case report: ZNF526-related Dentici-Novelli neurodevelopmental syndrome in two sibling","authors":"Yanhong Zhu , Xu Cao , Hui Yan , Yanping Fan , Weidong Zhao , Yujun Zhan , Hongli Zeng , Chaoyang Zhou , Zhenjie Chen , Li Yu , Jianguo Cao","doi":"10.1016/j.bdcasr.2025.100096","DOIUrl":"10.1016/j.bdcasr.2025.100096","url":null,"abstract":"<div><div>Background: <em>ZNF526</em> has been recently identified as a gene associated with Dentici-Novelli neurodevelopmental syndrome (DENNED), an autosomal recessive disorder characterized by global developmental delay, microcephaly, cataracts, and epilepsy. It very rarely happens in the East Asian population with only 3 cases currently.</div><div>Case presentation: In this case report, we present two sibling patients from China with a novel compound heterozygous variant (c.1512_1513del and c.1501C>A) in the <em>ZNF526</em> gene (NM_133444.3), expanding the phenotypic and geographic spectrum of DENNED. One patient's cranial MRI revealed widening of the extracerebral space in the bilateral frontotemporal region, abnormal EEG patterns, slow awake background activity, poor sleep background, and indistinguishable sleep cycles, which was never reported before. Our report also marks the first documentation of DENNED with this new <em>ZNF526</em> heterozygous variant around the world.</div><div>Discussion: With our case, we discuss all published 9 cases of <em>ZNF526</em> variants so far to enhance understanding of this rare disease and its clinical manifestations. We find that the reported DENNED in East Asia has some differences to cases in Europe and Middle East and there are some correlations between genetic variants and clinical manifestations.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report a 22-year-old Japanese man with severe congenital muscular dystrophy without intellectual disability due to a 3-kb retrotransposal insertion and point mutation in the fukutin gene (FKTN), classified as congenital muscular dystrophy-dystroglycanopathy without mental retardation (type B4; MDDGB4; OMIM 613152). The onset was in infancy, and while he eventually lost his ambulation, he had no intellectual disability.
Discussion
We believe that this patient had the most severe MDDGB4 phenotype not only among surviving patients with FKTN mutations but also among surviving patients with mutations in other α-dystroglycanopathy-related genes.
Conclusion
The phenotypes associated with FKTN mutations are not limited to FCMD, ranging from severe to mild in manifestation.
{"title":"Congenital muscular dystrophy due to fukutin mutations without ocular symptoms and central nervous system disorders: A case report","authors":"Hiroko Oiwa , Keiko Ishigaki , Yoshihiko Saito , Yasushi Oya , Ichizo Nishino , Yuji Takahashi","doi":"10.1016/j.bdcasr.2025.100095","DOIUrl":"10.1016/j.bdcasr.2025.100095","url":null,"abstract":"<div><h3>Case presentation</h3><div>We report a 22-year-old Japanese man with severe congenital muscular dystrophy without intellectual disability due to a 3-kb retrotransposal insertion and point mutation in the fukutin gene (<em>FKTN</em>), classified as congenital muscular dystrophy-dystroglycanopathy without mental retardation (type B4; MDDGB4; OMIM <span><span>613152</span><svg><path></path></svg></span>). The onset was in infancy, and while he eventually lost his ambulation, he had no intellectual disability.</div></div><div><h3>Discussion</h3><div>We believe that this patient had the most severe MDDGB4 phenotype not only among surviving patients with <em>FKTN</em> mutations but also among surviving patients with mutations in other α-dystroglycanopathy-related genes.</div></div><div><h3>Conclusion</h3><div>The phenotypes associated with <em>FKTN</em> mutations are not limited to FCMD, ranging from severe to mild in manifestation.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neurofibromatosis type 1 (NF1; OMIM 162200) is associated with various cardiovascular abnormalities, including moyamoya syndrome, which often leads to cerebral ischemia. However, symptomatic internal carotid artery (ICA) hypoplasia necessitating revascularization surgery has not been previously reported in patients with NF1. Here, we present a pediatric NF1 case involving symptomatic unilateral ICA hypoplasia associated with transient ischemic attacks.
Case presentation
Based on the presence of multiple café-au-lait spots and subcutaneous neurofibromas, a three-year-old girl, who presented at our hospital complaining of repeated episodes of transient right hemiparesis, was diagnosed with NF1. Head magnetic resonance imaging revealed an “ivy sign” in the left hemisphere on T2-fluid attenuated inversion recovery images. Cerebral angiography and magnetic resonance angiography revealed a left common carotid artery narrowing from its origin and a left ICA occlusion distal to the ophthalmic artery bifurcation. However, moyamoya vessels were not detected. Computed tomography scanning revealed a narrow left carotid canal, suggesting ICA hypoplasia. Cerebral perfusion imaging showed insufficient cerebral blood flow in the left middle cerebral artery territory. Therefore, the patient was diagnosed with symptomatic ICA hypoplasia associated with transient ischemic attacks, and revascularization surgery was performed.
Conclusion
ICA hypoplasia, a congenital ICA narrowing, is typically asymptomatic. This case indicates that vascular smooth muscle proliferation associated with NF1 may have contributed to symptomatic ICA occlusion and that in patients with NF1 and ICA hypoplasia, careful long-term observation may be required.
{"title":"A pediatric case of transient ischemic attacks associated with a hypoplastic internal carotid artery and neurofibromatosis type 1","authors":"Yuko Ushida , Yoshinori Kadono , Tomoko Nitta , Yuka Hattori , Satoshi Onishi , Yo Okizuka , Toyo Shimizu , Ren Matsushima , Kazushige Maeno , Atsuko Harada , Haruhiko Kishima","doi":"10.1016/j.bdcasr.2025.100094","DOIUrl":"10.1016/j.bdcasr.2025.100094","url":null,"abstract":"<div><h3>Background</h3><div>Neurofibromatosis type 1 (NF1; OMIM <span><span>162200</span><svg><path></path></svg></span>) is associated with various cardiovascular abnormalities, including moyamoya syndrome, which often leads to cerebral ischemia. However, symptomatic internal carotid artery (ICA) hypoplasia necessitating revascularization surgery has not been previously reported in patients with NF1. Here, we present a pediatric NF1 case involving symptomatic unilateral ICA hypoplasia associated with transient ischemic attacks.</div></div><div><h3>Case presentation</h3><div>Based on the presence of multiple café-au-lait spots and subcutaneous neurofibromas, a three-year-old girl, who presented at our hospital complaining of repeated episodes of transient right hemiparesis, was diagnosed with NF1. Head magnetic resonance imaging revealed an “ivy sign” in the left hemisphere on T2-fluid attenuated inversion recovery images. Cerebral angiography and magnetic resonance angiography revealed a left common carotid artery narrowing from its origin and a left ICA occlusion distal to the ophthalmic artery bifurcation. However, moyamoya vessels were not detected. Computed tomography scanning revealed a narrow left carotid canal, suggesting ICA hypoplasia. Cerebral perfusion imaging showed insufficient cerebral blood flow in the left middle cerebral artery territory. Therefore, the patient was diagnosed with symptomatic ICA hypoplasia associated with transient ischemic attacks, and revascularization surgery was performed.</div></div><div><h3>Conclusion</h3><div>ICA hypoplasia, a congenital ICA narrowing, is typically asymptomatic. This case indicates that vascular smooth muscle proliferation associated with NF1 may have contributed to symptomatic ICA occlusion and that in patients with NF1 and ICA hypoplasia, careful long-term observation may be required.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pyridoxine-dependent epilepsy (PDE) classically presents as neonatal seizures that are resistant to antiseizure medications (ASMs), but responsive to pyridoxine (vitamin B6). Clinical symptoms of patients with PDE are often diverse and non-specific. In addition, electroencephalography (EEG) and magnetic resonance imaging (MRI) findings in the brain are not fully understood.
Case presentation
Here, we report the case of a patient diagnosed with PDE at 12 months of age. A few hours after birth, the patient presented with various types of abnormal movements, including jerky, clonic, and spasmoid movements. Although burst suppression was obvious in the EEG during the early neonatal period, it disappeared, and only a dysmorphic pattern was observed after 2 weeks of age, without pyridoxine treatment. Because abnormal movements were sometimes resistant to ASMs, oral administration of pyridoxine was initiated at 1 month of age. However, this effect was not significant. Therefore, it was determined that there was no pyridoxine dependence, and pyridoxine was discontinued. Abnormal movements were remarkable after 2 months of age. EEG again showed burst suppression. MRI of the brain revealed progressive white matter atrophy. At 12 months of age, genetic testing revealed an ALDH7A1 mutation, which led to the diagnosis of PDE.
Conclusion
The characteristic abnormal movement in our case was spasmoid movement. Further investigation of EEG correspondence of the spasmoid movement is required. Burst suppression is a well-known EEG finding in PDE, but is not specific to PDE. Our case suggests that burst suppression severity varies depending on the time period.
{"title":"Disease progress in a patient with pyridoxine-dependent epilepsy, who was diagnosed at 12 months of age","authors":"Shunsuke Mizutani , Koya Kawase , Hisakazu Majima , Yuji Nakamura , Kaori Aiba , Seiji Watanabe , Tomoyuki Akiyama , Hirotomo Saitsu , Naomichi Matsumoto , Kenji Yokochi","doi":"10.1016/j.bdcasr.2025.100093","DOIUrl":"10.1016/j.bdcasr.2025.100093","url":null,"abstract":"<div><h3>Background</h3><div>Pyridoxine-dependent epilepsy (PDE) classically presents as neonatal seizures that are resistant to antiseizure medications (ASMs), but responsive to pyridoxine (vitamin B6). Clinical symptoms of patients with PDE are often diverse and non-specific. In addition, electroencephalography (EEG) and magnetic resonance imaging (MRI) findings in the brain are not fully understood.</div></div><div><h3>Case presentation</h3><div>Here, we report the case of a patient diagnosed with PDE at 12 months of age. A few hours after birth, the patient presented with various types of abnormal movements, including jerky, clonic, and spasmoid movements. Although burst suppression was obvious in the EEG during the early neonatal period, it disappeared, and only a dysmorphic pattern was observed after 2 weeks of age, without pyridoxine treatment. Because abnormal movements were sometimes resistant to ASMs, oral administration of pyridoxine was initiated at 1 month of age. However, this effect was not significant. Therefore, it was determined that there was no pyridoxine dependence, and pyridoxine was discontinued. Abnormal movements were remarkable after 2 months of age. EEG again showed burst suppression. MRI of the brain revealed progressive white matter atrophy. At 12 months of age, genetic testing revealed an <em>ALDH7A1</em> mutation, which led to the diagnosis of PDE.</div></div><div><h3>Conclusion</h3><div>The characteristic abnormal movement in our case was spasmoid movement. Further investigation of EEG correspondence of the spasmoid movement is required. Burst suppression is a well-known EEG finding in PDE, but is not specific to PDE. Our case suggests that burst suppression severity varies depending on the time period.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rapid-onset dystonia-parkinsonism (RDP) is a rare autosomal-dominant disorder caused by ATP1A3 variants. It is characterized by abrupt-onset asymmetrical dystonia, parkinsonism, and bulbar symptoms. Most cases present with sudden onset; however, atypical presentations with gradual onset have been rarely documented. In this report, we discuss the pathogenesis in a 28-year-old male patient with a rare ATP1A3 variant and atypical RDP manifestation.
Case report
A right-handed male patient developed handwriting difficulty and right-sided facial myoclonus at age 13, progressing to gradual dystonia predominantly affecting the right extremities. Neurological examinations at age 14 revealed right-sided dystonia, facial myoclonus, and bulbar symptoms without tremors or diurnal fluctuations. Brain MRI was normal, whereas single photon emission computed tomography (SPECT) showed hypoperfusion in the left basal ganglia associated with right-sided dystonia. Transcranial magnetic stimulation (TMS) clarified that the silent period, mediated by the gamma-aminobutyric acid (GABA)-B system, was normal. Genetic analysis identified a rare ATP1A3 variant (NM_152296.5):c.2438C>T,p.(Ala813Val) and confirmed it as de novo. Although oral medications, including levodopa, were ineffective, botulinum toxin (BT) therapy stabilized his dystonic symptoms for 13 years.
Discussion
This case highlights an atypical RDP presentation with gradual onset and minimal parkinsonism. Considering the results of SPECT and TMS, and the ineffectiveness of levodopa, one of the responsible lesions in this patient may be in the striatal output pathway rather than the dopaminergic system. The long-term effectiveness of BT therapy underscores its potential in managing dystonia in RDP.
{"title":"Atypical gradual progression in rapid-onset dystonia-parkinsonism with a rare ATP1A3 variant and the long-term effectiveness of botulinum toxin therapy","authors":"Kazuma Shinno , Masaya Kubota , Rika Kosaki , Kenjiro Kosaki , Akira Ishiguro","doi":"10.1016/j.bdcasr.2025.100092","DOIUrl":"10.1016/j.bdcasr.2025.100092","url":null,"abstract":"<div><h3>Background</h3><div>Rapid-onset dystonia-parkinsonism (RDP) is a rare autosomal-dominant disorder caused by <em>ATP1A3</em> variants. It is characterized by abrupt-onset asymmetrical dystonia, parkinsonism, and bulbar symptoms. Most cases present with sudden onset; however, atypical presentations with gradual onset have been rarely documented. In this report, we discuss the pathogenesis in a 28-year-old male patient with a rare <em>ATP1A3</em> variant and atypical RDP manifestation.</div></div><div><h3>Case report</h3><div>A right-handed male patient developed handwriting difficulty and right-sided facial myoclonus at age 13, progressing to gradual dystonia predominantly affecting the right extremities. Neurological examinations at age 14 revealed right-sided dystonia, facial myoclonus, and bulbar symptoms without tremors or diurnal fluctuations. Brain MRI was normal, whereas single photon emission computed tomography (SPECT) showed hypoperfusion in the left basal ganglia associated with right-sided dystonia. Transcranial magnetic stimulation (TMS) clarified that the silent period, mediated by the gamma-aminobutyric acid (GABA)-B system, was normal. Genetic analysis identified a rare <em>ATP1A3</em> variant (NM_152296.5):c.2438C>T,p.(Ala813Val) and confirmed it as <em>de novo</em>. Although oral medications, including levodopa, were ineffective, botulinum toxin (BT) therapy stabilized his dystonic symptoms for 13 years.</div></div><div><h3>Discussion</h3><div>This case highlights an atypical RDP presentation with gradual onset and minimal parkinsonism. Considering the results of SPECT and TMS, and the ineffectiveness of levodopa, one of the responsible lesions in this patient may be in the striatal output pathway rather than the dopaminergic system. The long-term effectiveness of BT therapy underscores its potential in managing dystonia in RDP.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-02DOI: 10.1016/j.bdcasr.2025.100091
Yuki Inami , Katsunori Fujii , Hiroko Tada
Background
Head banging is a sleep-related rhythmic movement disorder in children, characterized by sudden banging of the head on the crib headboard or side railing during sleep. It usually improves before 4 years of age, but may persist into adolescence owing to specific etiologies.
Case report
We describe the case of a 6-year-old Japanese girl who had exhibited prolonged head banging since the age of 6 months. As polysomnography revealed obstructive sleep apnea at age 6, adenoidectomy was performed to resolve her sleep disturbances. The head banging decreased dramatically after the adenoidectomy and was associated with reduced periodic limb movements, and increased long sleep fragmentation.
Discussion
Head banging is a subtype of sleep-related rhythmic movement disorder, which mainly affects infants and children. Sleep apnea reportedly causes sleep-related rhythmic movement disorders in adults; however, there have been only one report in children with head banging. We demonstrated that prolonged head banging was dramatically reduced by adenoidectomy, suggesting that obstructive sleep apnea could exacerbate head banging during childhood.
Conclusion
Head banging in children over 5 years of age has diverse etiologies. Obstructive sleep apnea could be considered one of the few possible causes of prolonged head banging.
{"title":"Prolonged head banging improved by adenoidectomy in a 6-year-old girl","authors":"Yuki Inami , Katsunori Fujii , Hiroko Tada","doi":"10.1016/j.bdcasr.2025.100091","DOIUrl":"10.1016/j.bdcasr.2025.100091","url":null,"abstract":"<div><h3>Background</h3><div>Head banging is a sleep-related rhythmic movement disorder in children, characterized by sudden banging of the head on the crib headboard or side railing during sleep. It usually improves before 4 years of age, but may persist into adolescence owing to specific etiologies.</div></div><div><h3>Case report</h3><div>We describe the case of a 6-year-old Japanese girl who had exhibited prolonged head banging since the age of 6 months. As polysomnography revealed obstructive sleep apnea at age 6, adenoidectomy was performed to resolve her sleep disturbances. The head banging decreased dramatically after the adenoidectomy and was associated with reduced periodic limb movements, and increased long sleep fragmentation.</div></div><div><h3>Discussion</h3><div>Head banging is a subtype of sleep-related rhythmic movement disorder, which mainly affects infants and children. Sleep apnea reportedly causes sleep-related rhythmic movement disorders in adults; however, there have been only one report in children with head banging. We demonstrated that prolonged head banging was dramatically reduced by adenoidectomy, suggesting that obstructive sleep apnea could exacerbate head banging during childhood.</div></div><div><h3>Conclusion</h3><div>Head banging in children over 5 years of age has diverse etiologies. Obstructive sleep apnea could be considered one of the few possible causes of prolonged head banging.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-23DOI: 10.1016/j.bdcasr.2025.100089
Tomomi Nakamura , Takahiro Yonekawa , Motomichi Kosuga , Minehiro Kurai , Hiroyuki Sakatoku , Tatsuyoshi Yamamoto , Pascal Yoshida , Yuji Sato , Takahiro Ito , Mari Morimoto , Ryo Hanaki , Hidemi Toyoda , Masahiro Hirayama
Background
Mucopolysaccharidosis type II (MPS II; Hunter syndrome), an X-linked recessive lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase, leads to systemic accumulations of glycosaminoglycans that affect multiple organs. It also has several distinctive cutaneous manifestations, in particular extensive Mongolian spots (dermal melanocytosis), which are often the earliest signs of the disease. The Mongolian spots in patients with MPS II are known to persist for much longer than they do in healthy children, and they are nonresponsive to hematopoietic stem cell transplantation or enzyme replacement therapy with idursulfase.
Case presentation
We report a case of extensive Mongolian spots extending upwards from the buttocks and on the abdomen in a Japanese boy who was diagnosed with neuronopathic MPS II at 15 months of age, whereupon treatment was started with weekly intravenous administration of pabinafusp alfa. After over 2 years of treatment, his neurocognitive development was maintained, and he showed no apparent somatic manifestations (e.g. hepatosplenomegaly, valvular dysfunctions or hearing loss), suggesting that pabinafusp alfa is effective in addressing both the neuronopathic and somatic symptoms of MPS II. Notably, the extensive Mongolian spots covering the patient's sacral and extrasacral regions resolved markedly in terms of both size and colour.
Discussion
This is the first report of improvements in MPS II-associated extensive Mongolian spots brought about by enzyme replacement therapy. Further study of MPS II-related skin lesions and their clinical course is required to elucidate the dermatological pathology of a disease that has hitherto been nonresponsive to conventional therapies.
{"title":"Resolution of extensive Mongolian spots (dermal melanocytosis) in a patient with mucopolysaccharidosis type II undergoing enzyme replacement therapy with pabinafusp alfa: A case report","authors":"Tomomi Nakamura , Takahiro Yonekawa , Motomichi Kosuga , Minehiro Kurai , Hiroyuki Sakatoku , Tatsuyoshi Yamamoto , Pascal Yoshida , Yuji Sato , Takahiro Ito , Mari Morimoto , Ryo Hanaki , Hidemi Toyoda , Masahiro Hirayama","doi":"10.1016/j.bdcasr.2025.100089","DOIUrl":"10.1016/j.bdcasr.2025.100089","url":null,"abstract":"<div><h3>Background</h3><div>Mucopolysaccharidosis type II (MPS II; Hunter syndrome), an X-linked recessive lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase, leads to systemic accumulations of glycosaminoglycans that affect multiple organs. It also has several distinctive cutaneous manifestations, in particular extensive Mongolian spots (dermal melanocytosis), which are often the earliest signs of the disease. The Mongolian spots in patients with MPS II are known to persist for much longer than they do in healthy children, and they are nonresponsive to hematopoietic stem cell transplantation or enzyme replacement therapy with idursulfase.</div></div><div><h3>Case presentation</h3><div>We report a case of extensive Mongolian spots extending upwards from the buttocks and on the abdomen in a Japanese boy who was diagnosed with neuronopathic MPS II at 15 months of age, whereupon treatment was started with weekly intravenous administration of pabinafusp alfa. After over 2 years of treatment, his neurocognitive development was maintained, and he showed no apparent somatic manifestations (e.g. hepatosplenomegaly, valvular dysfunctions or hearing loss), suggesting that pabinafusp alfa is effective in addressing both the neuronopathic and somatic symptoms of MPS II. Notably, the extensive Mongolian spots covering the patient's sacral and extrasacral regions resolved markedly in terms of both size and colour.</div></div><div><h3>Discussion</h3><div>This is the first report of improvements in MPS II-associated extensive Mongolian spots brought about by enzyme replacement therapy. Further study of MPS II-related skin lesions and their clinical course is required to elucidate the dermatological pathology of a disease that has hitherto been nonresponsive to conventional therapies.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-23DOI: 10.1016/j.bdcasr.2025.100090
Shonosuke Tagashira , Nobuko Katayama , Ai Kato , Yoichiro Oda
Background
One-and-a-half (OAAH) syndrome is defined as complete horizontal gaze palsy in one eye and medial gaze palsy in the other, while binocular convergence remains intact. This syndrome arises from concurrent damage to the unilateral medial longitudinal fasciculus and either the paramedian pontine reticular formation or abducens nerve nucleus within the pontine tegmentum.
Case presentation
A 7-year-old girl presented with acute onset nausea, vomiting, diplopia, and exotropia, occurring 4 weeks after influenza vaccination. Examination revealed preserved vertical gaze bilaterally with complete horizontal gaze palsy in the right eye and isolated adduction deficit in the left eye, while convergence remained intact. Neurological examination was otherwise unremarkable. Brain magnetic resonance imaging (MRI) demonstrated high signal intensity lesions in the pontine tegmentum, medulla oblongata, and cerebral white matter without gadolinium enhancement. Treatment with prednisolone rapidly resolved oculomotor deficits, and the patient remained asymptomatic with no new MRI lesions at 1 year follow-up.
Discussion
The patient was diagnosed with isolated OAAH syndrome. The cause was considered as clinically isolated syndrome (CIS) based on demyelinating changes on MRI in the region associated with OAAH syndrome and not meeting the criteria for acute disseminated encephalomyelitis or multiple sclerosis (MS). Isolated OAAH syndrome in the pediatric population is uncommon, with few case reports, including a case of MS. Furthermore, the association between influenza vaccinations and CIS remains unclear.
Conclusion
We reported a case of isolated OAAH syndrome caused by CIS in a pediatric population.
{"title":"A pediatric case of clinically isolated syndrome presenting with one-and-a-half syndrome","authors":"Shonosuke Tagashira , Nobuko Katayama , Ai Kato , Yoichiro Oda","doi":"10.1016/j.bdcasr.2025.100090","DOIUrl":"10.1016/j.bdcasr.2025.100090","url":null,"abstract":"<div><h3>Background</h3><div>One-and-a-half (OAAH) syndrome is defined as complete horizontal gaze palsy in one eye and medial gaze palsy in the other, while binocular convergence remains intact. This syndrome arises from concurrent damage to the unilateral medial longitudinal fasciculus and either the paramedian pontine reticular formation or abducens nerve nucleus within the pontine tegmentum.</div></div><div><h3>Case presentation</h3><div>A 7-year-old girl presented with acute onset nausea, vomiting, diplopia, and exotropia, occurring 4 weeks after influenza vaccination. Examination revealed preserved vertical gaze bilaterally with complete horizontal gaze palsy in the right eye and isolated adduction deficit in the left eye, while convergence remained intact. Neurological examination was otherwise unremarkable. Brain magnetic resonance imaging (MRI) demonstrated high signal intensity lesions in the pontine tegmentum, medulla oblongata, and cerebral white matter without gadolinium enhancement. Treatment with prednisolone rapidly resolved oculomotor deficits, and the patient remained asymptomatic with no new MRI lesions at 1 year follow-up.</div></div><div><h3>Discussion</h3><div>The patient was diagnosed with isolated OAAH syndrome. The cause was considered as clinically isolated syndrome (CIS) based on demyelinating changes on MRI in the region associated with OAAH syndrome and not meeting the criteria for acute disseminated encephalomyelitis or multiple sclerosis (MS). Isolated OAAH syndrome in the pediatric population is uncommon, with few case reports, including a case of MS. Furthermore, the association between influenza vaccinations and CIS remains unclear.</div></div><div><h3>Conclusion</h3><div>We reported a case of isolated OAAH syndrome caused by CIS in a pediatric population.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum to “Dihydropteridine reductase deficiency: The first Moroccan case report” [Brain Dev. Case Rep. 2(2) (2024) 100008]","authors":"Kaoutar Khabbache , Afaf Lamzouri , Hanaa Imlahi , Abdallah Oulmaati","doi":"10.1016/j.bdcasr.2025.100088","DOIUrl":"10.1016/j.bdcasr.2025.100088","url":null,"abstract":"","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to “Longitudinal study of EEG patterns in a child with a KCNH1 mutation showing non-epileptic myoclonus” [Brain Dev. Case Rep. 3(2) (2025) 100069]","authors":"Takeshi Inoue , Kei Ohashi , Ayako Hattori , Mariko Saito , Tomoshige Tanimura , Daisuke Ieda , Kyoko Ban , Fuyuki Miya , Shinji Saitoh","doi":"10.1016/j.bdcasr.2025.100087","DOIUrl":"10.1016/j.bdcasr.2025.100087","url":null,"abstract":"","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 3","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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