Brain and Development Case Reports最新文献_第4页

A pathogenic missense variant, c.2149G>A (p.Gly717Arg), in CDK13 in a female patient with CDK13-related disorder: A case report and literature review of 112 cases 一名患有 CDK13 相关疾病的女性患者 CDK13 中的致病性错义变异 c.2149G>A (p.Gly717Arg)：病例报告和 112 例文献综述

Brain and Development Case Reports

Pub Date : 2024-06-07 DOI: 10.1016/j.bdcasr.2024.100023

Naoki Morooka , Jun Kido , Hiroe Ueno , Yohei Misumi , Keishin Sugawara , Shinichi Kameyama , Hiromi Fukuda , Takeshi Mizuguchi , Naomichi Matsumoto , Mitsuharu Ueda , Kimitoshi Nakamura

Background

CDK13 (OMIM 603309), a cyclin-dependent kinase, phosphorylates RNA polymerase II and plays a role in various biological processes, including transcriptional regulation, alternative mRNA splicing, and axonal elongation. Patients with CDK13-related disorder present with facial abnormalities; hypotonia; congenital cardiac, renal, and skeletal abnormalities; and psychoneurological manifestations, including developmental delays, intellectual disabilities, and epilepsy.

Case presentation

We present the case of a 7-year-old female patient with CDK13-related disorder. The patient had peculiar facial features, such as microcephaly, hypertelorism, broad nasal root and alar, frontal hypertrichosis, small jaw and low auricle, and atrial septal defect. Additionally, she presented with hypotonia and developmental delays. Her developmental delay was remarkable with her age and her total developmental quotient on the Kyoto Scale of Psychological Development 2020 was 38 (postural-motor, 40; cognitive-adaptive, 41; and language-social, 34) at 7 years and 8 months of age. Her cognitive development was progressing slowly at her own pace, with support from social interactions, physiotherapy, and occupational therapy. Moreover, facial dysmorphism, developmental delays, and intellectual disabilities were highly frequent even among the 15 patients with the CDK13 c.2149G>A (p.Gly717Arg) variant through the literature review.

Conclusion

Patients with CDK13-related disorder typically exhibit facial dysmorphism, developmental delays, and intellectual disabilities, with the possibility of additional manifestations emerging in adulthood. This patient also presented the same manifestations as those of other patients with CDK13-related disorder. Clinical outcomes should be followed up for a long duration in this patient, as various clinical manifestations and problems may be expected.

背景CDK13（OMIM 603309）是一种细胞周期蛋白依赖性激酶，可使 RNA 聚合酶 II 磷酸化，并在转录调控、mRNA 替代剪接和轴突伸长等多种生物过程中发挥作用。CDK13 相关疾病患者表现为面部畸形；肌张力低下；先天性心脏、肾脏和骨骼异常；以及精神神经系统表现，包括发育迟缓、智力障碍和癫痫。患者面部特征奇特，如小头畸形、脊柱后凸、鼻根和鼻翼宽大、额叶肥厚、小下颌和低耳廓以及房间隔缺损。此外，她还伴有肌张力低下和发育迟缓。她的发育迟缓与年龄不符，7 岁 8 个月时，她在 2020 年京都心理发育量表中的总发育商数为 38（姿势-运动，40；认知-适应，41；语言-社交，34）。在社会交往、物理治疗和职业治疗的支持下，她的认知发展按照自己的节奏缓慢前进。此外，通过文献回顾，即使在15例CDK13 c.2149G>A（p.Gly717Arg）变异患者中，面部畸形、发育迟缓和智力障碍也非常常见。该患者的表现与其他 CDK13 相关障碍患者相同。由于可能会出现各种临床表现和问题，因此应对该患者的临床结果进行长期随访。

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引用次数: 0

Hypohidrotic ectodermal dysplasia with influenza-associated encephalopathy: A case report 下皮外胚层发育不良伴流感相关脑病：病例报告

Brain and Development Case Reports

Pub Date : 2024-06-01 DOI: 10.1016/j.bdcasr.2024.100018

Takanobu Yoshida , Jun Kido , Mika Ogata , Tomoyuki Mizukami , Katsuki Hirai , Yohei Misumi , Toshiyuki Itai , Satoko Miyatake , Naomichi Matsumoto , Mitsuharu Ueda , Kimitoshi Nakamura

Background

Pathogenic variants of ectodysplasin A (EDA) gene are responsible for the development of hypohidrotic ectodermal dysplasia (HED) and energy dysmetabolism. Patients with HED develop hyperthermia and dry skin owing to hypohidrosis. Influenza-associated encephalopathy (IAE) is characterized by developing impaired consciousness within a few days after influenza infection.

Case presentation

A 4-year-old boy with HED demonstrated IAE. He experienced frequent episodes of fever and exhibited typical HED features such as sparse hair, hypohidrosis, and dry skin. He was diagnosed with IAE at the age of 19 months and showed severe psychomotor impairment after this diagnosis.

Discussion

Cytokine storm, status epilepticus, and significant hyperthermia deriving from HED during influenza virus infection were determined to have contributed to the development of IAE resulting in defective energy metabolism and neuronal damage.

Conclusion

Cytokine storm and significant hyperthermia during the influenza virus infection might cause the development of IAE and enhance catabolism. Thermal control is essential for HED management. Therefore, controlling body temperature during the infectious viral state is essential.

背景外胚层发育不良（HED）和能量代谢障碍是外胚层发育蛋白 A（EDA）基因致病变异的原因。HED 患者会因缺水而出现高热和皮肤干燥。流感相关脑病（IAE）的特点是在感染流感后几天内出现意识障碍。他经常发烧，并表现出典型的 HED 特征，如毛发稀疏、多汗和皮肤干燥。讨论流感病毒感染期间的细胞因子风暴、癫痫状态和 HED 引起的显著高热被确定为导致 IAE 的发生，造成能量代谢缺陷和神经元损伤。体温控制对 HED 管理至关重要。因此，在病毒感染状态下控制体温至关重要。

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引用次数: 0

Biotinidase deficiency: A treatable neurometabolic disorder 生物素酶缺乏症：一种可治疗的神经代谢疾病

Brain and Development Case Reports

Pub Date : 2024-05-25 DOI: 10.1016/j.bdcasr.2024.100021

Beena Devanapalli , Rachel Sze Hui Wong , Natalie Lim , P Ian Andrews , Keshini Vijayan , Won-Tae Kim , Tiffany Wotton , Esther Tantsis , Enzo Ranieri , Adviye Ayper Tolun , Shanti Balasubramaniam

Background

Biotinidase (E.C. 3.5.1.12) is an enzyme which recycles biotin, a coenzyme of four carboxylases involved in fatty acid synthesis, amino acid catabolism and gluconeogenesis. Biotinidase deficiency (OMIM #253260) causes a reduction in free biotin leading to multiple carboxylase deficiency. In its severe form, children may have seizures, delayed development, respiratory issues, cutaneous manifestations, hearing and visual loss. The milder phenotype may manifest symptoms only when stressed, such as during infections.

Case presentation

We describe two infants who presented aged two and five months respectively, with generalised seizures, mild gross motor delay, elevated plasma and cerebrospinal fluid lactate levels. Moderate increases in propionylcarnitine and 3-hydroxyisovalerylcarnitine on plasma acylcarnitine profile suggested multiple carboxylase deficiency. Further testing confirmed biotinidase deficiency. Retrospective qualitative analysis of the newborn screening dried blood spot cards in both patients showed reduced biotinidase enzyme activity. Molecular analysis confirmed pathogenic homozygous variants in the BTD gene. They were commenced on oral biotin with no further seizures observed in either patient. Patient 1 also made significant developmental gains and achieved age-appropriate milestones by 12 months. At five years of age, he has receptive and expressive language delays.

Discussion/conclusion

Early identification and treatment of biotinidase deficiency can prevent lifelong complications and major disabilities, hence should be considered as an important differential of seizures and neurodevelopmental delay. Currently, biotinidase deficiency is not one of the conditions screened for in newborns in Australia, however with the evolving demographics due to robust immigration, the New South Wales Newborn Screening Program has reconsidered its inclusion in our screening program.

背景生物素酶（E.C. 3.5.1.12）是一种回收生物素的酶，生物素是参与脂肪酸合成、氨基酸分解和葡萄糖生成的四种羧化酶的辅酶。生物素酶缺乏症（OMIM #253260）会导致游离生物素减少，从而导致多种羧化酶缺乏症。重症患儿可能会出现癫痫发作、发育迟缓、呼吸系统问题、皮肤表现、听力和视力下降。我们描述了两名分别为两个月大和五个月大的婴儿的病例，他们出现全身抽搐、轻度大运动迟缓、血浆和脑脊液乳酸水平升高。血浆酰基肉碱谱中丙酰肉碱和 3-羟基异戊酰基肉碱的中度升高表明他们缺乏多种羧化酶。进一步检测证实了生物素酶缺乏症。对两名患者的新生儿筛查干血斑卡进行的回顾性定性分析显示，生物素酶活性降低。分子分析证实了 BTD 基因的致病性同源变异。开始口服生物素后，两名患者均未再出现癫痫发作。患者 1 在发育方面也取得了显著进步，在 12 个月时达到了与年龄相适应的发育里程碑。讨论/结论及早发现和治疗生物素缺乏症可预防终生并发症和重大残疾，因此应将其作为癫痫发作和神经发育迟缓的重要鉴别依据。目前，生物素缺乏症并不是澳大利亚新生儿筛查的病症之一，但随着移民人口的不断增加，新南威尔士州新生儿筛查计划已重新考虑将其纳入筛查项目。

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引用次数: 0

Cerebrospinal fluid leakage after COVID-19: A pediatric case COVID-19 后脑脊液漏：一个儿科病例

Brain and Development Case Reports

Pub Date : 2024-05-22 DOI: 10.1016/j.bdcasr.2024.100019

Rika Tobiume , Yukihiko Konishi , Kosuke Koyano , Shinji Nakamura , Sae Nishisho , Takayuki Wakabayashi , Noriko Fuke , Ami Mizuo , Takuma Iwaki , Takashi Kusaka

Background

Various neurological and psychiatric symptoms have emerged after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus that causes coronavirus disease 2019 (COVID-19). These symptoms include exercise intolerance such as muscle weakness, fatigue, and pain as well as cognitive and mood disorders (brain fog). Further, frequent autonomic disorders such as hypotension and hypothermia have been recognized in adults and children, many of whom have been diagnosed with orthostatic dysregulation (OD). Some children with OD have developed cerebrospinal fluid leakage (CFL).

Case Presentation

Herein, we describe the case of a boy aged 9 years and 9 months who presented with orthostatic headaches, dizziness, and nausea. He was diagnosed with CFL after SARS-CoV-2 infection when a spinal MRI revealed an incomplete floating dural sac sign in the thoracic and lumbar spine. An epidural saline injection was administered, and he was discharged after his symptoms improved.

Discussion/Conclusion

The causes of CFL include trauma due to accidents or sports, or are idiopathic due to unknown causes. However, the onset of CFL might involve COVID-19. Understanding the relationship between COVID-19 and CFL onset may lead to better treatment outcomes for children with apparent symptoms of OD, such as orthostatic headaches, dizziness, and nausea, after contracting COVID-19.

背景感染严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）（即导致 2019 年冠状病毒病（COVID-19）的病毒）后，出现了各种神经和精神症状。这些症状包括运动不耐受，如肌肉无力、疲劳和疼痛，以及认知和情绪障碍（脑雾）。此外，成人和儿童经常出现低血压和低体温等自律神经失调，其中许多人被诊断为正张力失调（OD）。在此，我们描述了一个 9 岁零 9 个月的男孩的病例，他出现了正位性头痛、头晕和恶心。他在感染 SARS-CoV-2 后，脊柱磁共振成像显示胸椎和腰椎有不完整的硬膜囊漂浮征，因此被诊断为 CFL。讨论/结论 CFL 的病因包括事故或运动造成的外伤，或原因不明的特发性病因。然而，CFL的发病可能与COVID-19有关。了解 COVID-19 与 CFL 发病之间的关系，可能会为感染 COVID-19 后出现正压性头痛、头晕和恶心等明显 OD 症状的儿童带来更好的治疗效果。

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引用次数: 0

Dramatic benzodiazepine receptor downregulation observed in holoprosencephaly with drug-resistant epilepsy 在伴有耐药性癫痫的全脑畸形中观察到苯并二氮杂卓受体的急剧下调

Brain and Development Case Reports

Pub Date : 2024-05-21 DOI: 10.1016/j.bdcasr.2024.100020

Kousuke Nakamura , Sayaka Ishii , Kei Tamaru , Takeshi Inukai , Masao Aihara , Yoshimi Kaga

Background

Holoprosencephaly (HPE), a central nervous system malformation caused by a defect in the separation of cerebral hemispheres during development, is associated with drug-resistant epilepsy. Animal studies on HPE have suggested its association with dysplasia of the inhibitory interneurons in the cerebral cortex; however, this association has not been reported in patients with HPE. In this study, we presented cases of three children with HPE who were examined for the distribution of benzodiazepine receptors, which are receptors of the inhibitory system, using ¹²³I-iomazenil single-photon emission computed tomography (SPECT).

Case presentation

All three children had drug-resistant epilepsy with frequent daily seizures. ^99mTc ethyl cysteinate dimer (ECD) SPECT and ¹²³I-iomazenil SPECT were performed to evaluate the epileptogenicity. ^99mTc ECD SPECT showed generalized only cerebral hypoperfusion, and ¹²³I-iomazenil SPECT showed widespread benzodiazepine receptor depression in the cerebrum, thalamus, and brainstem. Although, benzodiazepines, including clonazepam, clobazam, and lorazepam have limited effects on epileptic seizures, the addition of levetiracetam led to the reduction in seizure frequency in all three patients.

Conclusion

The SPECT findings in children with HPE suggested a defect in the development of GABAergic-benzodiazepinergic inhibitory neurons, especially in the thalamus and brainstem. Therefore, it is inferred that conventional antiepileptic drugs that potentiate the mechanisms of inhibitory neurons are less effective. Agents, with alternative mechanisms of action may be useful for the treatment of refractory epilepsy.

背景颅脑发育不全（HPE）是一种中枢神经系统畸形，由发育过程中大脑半球分离缺陷引起，与耐药性癫痫有关。有关 HPE 的动物实验表明，HPE 与大脑皮层抑制性中间神经元发育不良有关；然而，在 HPE 患者中还没有这种关联的报道。在本研究中，我们利用 123I-iomazenil 单光子发射计算机断层扫描（SPECT）对三名 HPE 患儿的苯二氮卓受体（抑制系统受体）分布情况进行了检查。为了评估致痫性，他们接受了99m锝半胱氨酸乙二酯（ECD）SPECT和123I-碘马泽尼SPECT检查。99mTc 乙半胱氨酸二聚体（ECD）SPECT 显示患者只有全身性脑灌注不足，而 123I-iomazenil SPECT 则显示大脑、丘脑和脑干存在广泛的苯并二氮杂卓受体抑制。尽管包括氯硝西泮、氯巴泮和劳拉西泮在内的苯二氮卓类药物对癫痫发作的影响有限，但加入左乙拉西坦后，三名患者的癫痫发作频率均有所降低。因此，可以推断增强抑制性神经元机制的传统抗癫痫药物效果较差。具有其他作用机制的药物可能有助于治疗难治性癫痫。

{"title":"Dramatic benzodiazepine receptor downregulation observed in holoprosencephaly with drug-resistant epilepsy","authors":"Kousuke Nakamura , Sayaka Ishii , Kei Tamaru , Takeshi Inukai , Masao Aihara , Yoshimi Kaga","doi":"10.1016/j.bdcasr.2024.100020","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100020","url":null,"abstract":"<div><h3>Background</h3><p>Holoprosencephaly (HPE), a central nervous system malformation caused by a defect in the separation of cerebral hemispheres during development, is associated with drug-resistant epilepsy. Animal studies on HPE have suggested its association with dysplasia of the inhibitory interneurons in the cerebral cortex; however, this association has not been reported in patients with HPE. In this study, we presented cases of three children with HPE who were examined for the distribution of benzodiazepine receptors, which are receptors of the inhibitory system, using <sup>123</sup>I-iomazenil single-photon emission computed tomography (SPECT).</p></div><div><h3>Case presentation</h3><p>All three children had drug-resistant epilepsy with frequent daily seizures. <sup>99m</sup>Tc ethyl cysteinate dimer (ECD) SPECT and <sup>123</sup>I-iomazenil SPECT were performed to evaluate the epileptogenicity. <sup>99m</sup>Tc ECD SPECT showed generalized only cerebral hypoperfusion, and <sup>123</sup>I-iomazenil SPECT showed widespread benzodiazepine receptor depression in the cerebrum, thalamus, and brainstem. Although, benzodiazepines, including clonazepam, clobazam, and lorazepam have limited effects on epileptic seizures, the addition of levetiracetam led to the reduction in seizure frequency in all three patients.</p></div><div><h3>Conclusion</h3><p>The SPECT findings in children with HPE suggested a defect in the development of GABAergic-benzodiazepinergic inhibitory neurons, especially in the thalamus and brainstem. Therefore, it is inferred that conventional antiepileptic drugs that potentiate the mechanisms of inhibitory neurons are less effective. Agents, with alternative mechanisms of action may be useful for the treatment of refractory epilepsy.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 2","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000163/pdfft?md5=5a3443e732e6a17a1c88ae76703d0f91&pid=1-s2.0-S2950221724000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Progress in cardiorespiratory fitness and motor coordination skills in children with attention-deficit/hyperactivity disorder with easy fatigue and physical inactivity due to the side effects of guanfacine extended-release 因服用胍法辛缓释片的副作用而容易疲劳和缺乏运动的注意力缺陷/多动障碍儿童在心肺功能和运动协调能力方面的进步

Brain and Development Case Reports

Pub Date : 2024-04-30 DOI: 10.1016/j.bdcasr.2024.100017

Ken Kikuchi , Midori Hayashi , Manami Honda

Introduction

Guanfacine extended-release (GXR), a medication administered to treat attention-deficit/hyperactivity disorder (ADHD), demonstrates side effects, including hypotension, bradycardia, sedation, and somnolence. Children with ADHD with easy fatigue and physical inactivity caused by these side effects have been reported in clinical practice. ADHD medications improve motor function in the short term. Herein, we report the progress in cardiorespiratory fitness (CRF) and motor function of children with ADHD with easy fatigue and physical inactivity after GXR treatment.

Case presentation

A 7-year-old patient with ADHD began to demonstrate marked fatigue and physical inactivity after taking GXR. His treatment was then combined with physical therapy which was continued once a month for approximately one year and included a treadmill exercise test (10-minute walk with a multistep load protocol of 3.0–8.0 km/h) and instruction in motor coordination skills, including home exercises. The GXR dose was increased approximately every 9–10 months, considering the weight and increasing problems at home. Motor coordination skills improved immediately after the increased GXR dose, and the CRF progressed well as the effect of medication subsided.

Discussion/Conclusion

Fatigue and physical inactivity should be considered in exercise therapy in combination with GXR administration. Thus, combined exercise therapy and medication that considers CRF and skill acquisition status may be effective for children with ADHD.

导言胍法辛缓释片（GXR）是一种治疗注意力缺陷/多动障碍（ADHD）的药物，具有低血压、心动过缓、镇静和嗜睡等副作用。在临床实践中，有报道称患有多动症的儿童因这些副作用而容易疲劳和不爱运动。多动症药物可在短期内改善运动功能。病例介绍一位 7 岁的多动症患者在服用 GXR 后开始表现出明显的疲劳和肢体不活动。随后，他接受了物理治疗，治疗持续了大约一年，每月一次，包括跑步机运动测试（10 分钟步行，3.0-8.0 公里/小时的多步负重方案）和运动协调技能指导，包括家庭练习。考虑到体重和家庭问题的增加，GXR 的剂量大约每 9-10 个月增加一次。增加 GXR 剂量后，运动协调能力立即得到改善，随着药物效果的减弱，CRF 进展良好。因此，考虑到CRF和技能掌握情况的运动疗法与药物治疗相结合，可能对多动症儿童有效。

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引用次数: 0

ATP1A3 potentially causes hereditary spastic paraplegia: A case report of a patient presenting with lower limb spasticity and intellectual disability ATP1A3 可能导致遗传性痉挛性截瘫：一名下肢痉挛和智力障碍患者的病例报告

Brain and Development Case Reports

Pub Date : 2024-04-23 DOI: 10.1016/j.bdcasr.2024.100016

Satomi Okano , Yoshio Makita , Yuki Ueda , Akie Miyamoto , Hajime Tanaka , Kumiko Yanagi , Tadashi Kaname

Background

Sodium/potassium (Na⁺/K⁺) ATPase is a heteromeric protein complex responsible for maintaining the Na⁺/K⁺ electrochemical gradient across the neuronal plasma membrane. The α₃ isoform of the Na⁺/K⁺ ATPase, encoded by ATP1A3, acts as a rescue pump and is predominantly present in the neurons of the central nervous system. The de novo variants of ATP1A3 cause several distinct neurological syndromes.

Case

We presented the case of a boy with no family history of neurological diseases who was harboring a de novo pathogenic variation, NM_152296:c.974G > T, p.Gly325Val, in ATP1A3. He presented with a rare spastic paraplegia of the lower extremities, autism spectrum disorder, and intellectual disability.

Discussion and conclusion

Previous studies have demonstrated the ATP1A3 variant p.Gly325 to be pathogenic for dystonia, face dysmorphia, encephalopathy, brain magnetic resonance imaging abnormalities, and no hemiplegia. A recent study has revealed, for the first time, the development of spastic paraplegia as a manifestation of the de novo ATP1A3 p.Pro775Leu pathogenic variant. In this case report, we concluded that another de novo pathogenic variation in ATP1A3, p.Gly325Val, manifests as spastic paraplegia and intellectual disability in the index patient. These results suggest that ATP1A3 is a novel causative gene of hereditary spastic paraplegia.

背景钠/钾（Na+/K+）ATP酶是一种异构蛋白复合物，负责维持神经元质膜上的Na+/K+电化学梯度。由 ATP1A3 编码的 Na+/K+ ATPase 的 α3 异构体是一种救援泵，主要存在于中枢神经系统的神经元中。ATP1A3 的新生变异可导致几种不同的神经系统综合征。本病例中，一名无神经系统疾病家族史的男孩携带 ATP1A3 的新生致病变异 NM_152296:c.974G>T,p.Gly325Val。讨论与结论以往的研究表明，ATP1A3变异p.Gly325是肌张力障碍、面部畸形、脑病、脑磁共振成像异常的致病基因，但没有出现偏瘫。最近的一项研究首次发现，痉挛性截瘫的发生是新生 ATP1A3 p.Pro775Leu 致病变异体的一种表现。在这一病例报告中，我们得出结论，ATP1A3 的另一个从头致病变异 p.Gly325Val 在该例患者中表现为痉挛性截瘫和智力残疾。这些结果表明，ATP1A3 是遗传性痉挛性截瘫的新型致病基因。

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引用次数: 0

A case of SCN8A-related developmental epileptic encephalopathy diagnosed by clinical speculation driven targeted DNA sequencing and remission of epilepsy by sodium channel blockers combination therapy 一例通过临床猜测驱动的靶向DNA测序诊断出的SCN8A相关发育性癫痫脑病，钠通道阻滞剂联合疗法缓解了癫痫症状

Brain and Development Case Reports

Pub Date : 2024-04-11 DOI: 10.1016/j.bdcasr.2024.100015

Yoshitaka Mitsui , Hitoshi Sato , Sumihito Togi , Hiroki Ura , Yo Niida

Background

SCN8A-related epilepsy and/or neurodevelopmental disorders encompass a very broad spectrum of phenotypes. The most severe form, SCN8A developmental and epileptic encephalopathy (DEE), develops intractable epilepsy from early infancy and can lead to sudden death. Early diagnosis and therapeutic intervention are essential, but diagnosis is based on genetic testing and definitive diagnosis is often delayed.

Case report

A 4-month-old girl presented with intractable epilepsy. Most antiepileptic drugs were ineffective, but high doses of phenytoin suppressed seizures, so a sodium channelopathy was suspected and targeted DNA sequencing was performed, which revealed a pathogenic missense variant Val1315Met in the SCN8A gene. Based on the diagnosis, combination therapy with sodium channel blockers (SCBs) was initiated and the seizures resolved.

Conclusion

We experienced SCN8A-DEE, which led to early diagnosis based on clinical course and improved prognosis. It is noteworthy that even when the effect of a single SCB is insufficient, as in this case, combination therapy can lead to seizure free in SCN8A-DEE.

背景SCN8A相关癫痫和/或神经发育障碍包括非常广泛的表型。最严重的形式是 SCN8A 发育性癫痫脑病（DEE），从婴儿早期就会出现难治性癫痫，并可能导致猝死。早期诊断和治疗干预是至关重要的，但诊断是以基因检测为基础的，明确诊断往往被延迟。大多数抗癫痫药物无效，但大剂量苯妥英可抑制癫痫发作，因此怀疑是钠通道病变，并进行了有针对性的 DNA 测序，结果发现 SCN8A 基因中存在致病性错义变异 Val1315Met。根据诊断结果，患者开始接受钠通道阻滞剂（SCBs）联合治疗，癫痫发作得到缓解。值得注意的是，即使像本病例一样单用一种钠通道阻滞剂效果不佳，联合治疗也能使 SCN8A-DEE 不再发作。

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引用次数: 0

Long-term follow-up case of 14q12 deletion syndrome: A case report 14q12 缺失综合征的长期随访病例：病例报告

Brain and Development Case Reports

Pub Date : 2024-04-05 DOI: 10.1016/j.bdcasr.2024.100013

Yu Aihara , Noriko Sumitomo , Yuko Shimizu-Motohashi , Ken Inoue , Yu-ichi Goto , Hirofumi Komaki

Background

14q12 deletion syndrome is characterized by hypotonia, postnatal microcephaly, intellectual disability, epilepsy, involuntary movements, and loss of corpus callosum. Reported cases described only the childhood period, resulting in the scarcity of information on its long-term clinical course up to adulthood.

Case presentation

We herein present a 40-year-old man with 14q12 deletion. He has never acquired head control and speech and is bedridden with spastic quadriplegia, joint contractures, scoliosis, and chorea. During the first few years, functional movements were observed, which gradually disappeared. Brain magnetic resonance imaging revealed partial hypoplasia of the corpus callosum. At 19 years, a feeding tube was placed, and at 21 years, tracheostomy was introduced due to recurrent aspiration pneumonia. Although the patient experienced tonic seizures from infancy, they disappeared at 20 years of age. Microarray comparative genomic hybridization (CGH) test at age 40 confirmed a 3.95-Mb heterozygous deletion on 14q12, encompassing FOXG1, NOVA1, C14orf23, and PRKD1. The deletion was considered to be the cause of this case.

Conclusion

The present case describes the characteristic features and long-term clinical course of a patient with 14q12 deletion syndrome. Health issues associated with dysphagia and respiration could be prominent in the mid- to late teens, and seizures may be less problematic at adulthood.

背景14q12缺失综合征以肌张力低下、出生后小头畸形、智力障碍、癫痫、不自主运动和胼胝体缺失为特征。已报道的病例仅描述了儿童期的情况，因此有关该病直至成年期的长期临床过程的资料很少。他从未学会控制头部和说话，因痉挛性四肢瘫痪、关节挛缩、脊柱侧弯和舞蹈症而卧床不起。在最初几年，他曾有过功能性运动，但后来逐渐消失。脑磁共振成像显示胼胝体部分发育不良。19 岁时，患者被安置了喂食管，21 岁时，由于反复出现吸入性肺炎，患者被实施了气管切开术。虽然患者从婴儿期开始就有强直性癫痫发作，但在 20 岁时这种症状消失了。40岁时进行的微阵列比较基因组杂交（CGH）检测证实，14q12上有一个3.95兆的杂合缺失，包括FOXG1、NOVA1、C14orf23和PRKD1。本病例描述了一名 14q12 缺失综合征患者的特征和长期临床过程。与吞咽困难和呼吸困难相关的健康问题可能在十几岁中后期比较突出，而癫痫发作可能在成年后问题较少。

{"title":"Long-term follow-up case of 14q12 deletion syndrome: A case report","authors":"Yu Aihara , Noriko Sumitomo , Yuko Shimizu-Motohashi , Ken Inoue , Yu-ichi Goto , Hirofumi Komaki","doi":"10.1016/j.bdcasr.2024.100013","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100013","url":null,"abstract":"<div><h3>Background</h3><p>14q12 deletion syndrome is characterized by hypotonia, postnatal microcephaly, intellectual disability, epilepsy, involuntary movements, and loss of corpus callosum. Reported cases described only the childhood period, resulting in the scarcity of information on its long-term clinical course up to adulthood.</p></div><div><h3>Case presentation</h3><p>We herein present a 40-year-old man with 14q12 deletion. He has never acquired head control and speech and is bedridden with spastic quadriplegia, joint contractures, scoliosis, and chorea. During the first few years, functional movements were observed, which gradually disappeared. Brain magnetic resonance imaging revealed partial hypoplasia of the corpus callosum. At 19 years, a feeding tube was placed, and at 21 years, tracheostomy was introduced due to recurrent aspiration pneumonia. Although the patient experienced tonic seizures from infancy, they disappeared at 20 years of age. Microarray comparative genomic hybridization (CGH) test at age 40 confirmed a 3.95-Mb heterozygous deletion on 14q12, encompassing <em>FOXG1</em>, <em>NOVA1</em>, <em>C14orf23</em>, and <em>PRKD1</em>. The deletion was considered to be the cause of this case.</p></div><div><h3>Conclusion</h3><p>The present case describes the characteristic features and long-term clinical course of a patient with 14q12 deletion syndrome. Health issues associated with dysphagia and respiration could be prominent in the mid- to late teens, and seizures may be less problematic at adulthood.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 2","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000096/pdfft?md5=444a8a22d4b1a4c20b29b4d12e207762&pid=1-s2.0-S2950221724000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140346861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

First reported pediatric case of left internal carotid artery stenosis in myelin oligodendrocyte glycoprotein antibody-associated disease 首例报道的髓鞘少突胶质细胞糖蛋白抗体相关疾病左侧颈内动脉狭窄儿科病例

Brain and Development Case Reports

Pub Date : 2024-04-03 DOI: 10.1016/j.bdcasr.2024.100014

Eri Hasegawa , Jun Kubota , Taku Gomi , Shuntaro Terayama , Taiki Homma , Haruna Suzuki , Yoichi Takemasa , Ryota Saito , Kenta Horimukai , Noriko Takahata

Background

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) mimics the clinical and imaging findings of small-vessel central nervous system (CNS) angiitis. An adult case of MOGAD causing right middle cerebral artery stenosis was reported in 2023. Here, we present the first reported pediatric case of left internal carotid artery stenosis in a patient with MOGAD.

Case presentation

A previously healthy 13-year-old boy presented with a two-day history of fever and headache. He experienced sudden focal-onset impaired awareness tonic seizures on the right side, with right ocular deviation. Seizure activity ceased within 5 min, but unconsciousness and paralysis of the right face and right upper extremity persisted on admission. There were no other abnormal neurological findings. Blood tests revealed mildly elevated levels of inflammatory markers. Cerebrospinal fluid examination revealed a normal protein level of 39.3 mg/dL but an elevated cell count of 154/µL and an oligoclonal band. Fluid-attenuated inversion recovery MRI sequences revealed hyperintensities in the left basal ganglia and left frontoparietal cortex. Magnetic resonance angiography revealed left internal carotid artery stenosis. Subsequently, MOGAD was diagnosed based on a positive MOG antibody test result. He received three courses of methylprednisolone pulse therapy followed by oral prednisolone for 10 weeks. His symptoms, parenchymal brain lesions, and vascular stenosis all improved with treatment.

Discussion/Conclusion

MOGAD may be associated with vascular stenosis by inducing a perivascular immune response. MOGAD may mimic CNS angiitis, including that of medium- and large-sized vessels. The presence of vascular stenosis does not rule out MOGAD.

背景髓鞘少突胶质细胞糖蛋白（MOG）抗体相关疾病（MOGAD）模仿小血管中枢神经系统（CNS）血管炎的临床和影像学表现。2023 年报道了一例 MOGAD 导致右侧大脑中动脉狭窄的成人病例。在此，我们介绍首例MOGAD患者左侧颈内动脉狭窄的儿科病例。病例介绍一名之前身体健康的13岁男孩，两天前出现发热和头痛。他突然出现右侧局灶性意识障碍强直发作，伴右眼偏斜。发作活动在 5 分钟内停止，但入院时仍昏迷不醒，右脸和右上肢瘫痪。神经系统没有其他异常发现。血液检查显示炎症标志物水平轻度升高。脑脊液检查显示蛋白质水平正常，为 39.3 mg/dL，但细胞计数升高至 154 个/μL，并出现一条寡克隆带。体液减弱反转恢复磁共振成像序列显示左侧基底节和左侧额顶叶皮层高密度。磁共振血管造影显示左侧颈内动脉狭窄。随后，根据 MOG 抗体检测阳性结果，他被诊断为 MOGAD。他接受了三个疗程的甲基强的松龙脉冲治疗，随后口服强的松龙10周。讨论/结论MOGAD可能通过诱导血管周围免疫反应而与血管狭窄有关。MOGAD 可模拟中枢神经系统血管炎，包括中型和大型血管炎。血管狭窄的存在并不能排除 MOGAD 的可能性。

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引用次数: 0