Pub Date : 2024-12-01DOI: 10.1016/j.spen.2024.101169
John Collyer, Deepa S Rajan
Ataxia telangiectasia (AT) is a rare neurocutaneous syndrome that results from biallelic pathogenic variants in the ataxia telangiectasia mutated (ATM) gene, named for its characteristic cerebellar ataxia in the early toddler years and variable oculocutaneous telangiectasias in the school age years. While its name only hints at neurologic and cutaneous manifestations, this multisystemic disorder also has important immunologic, oncologic, respiratory, and endocrinologic implications. This article will review the function of the ATM gene, the neurologic manifestations of AT, non-neurologic complications, mimickers of AT (including other disorders of defective DNA repair), and the realm of therapeutic research for AT.
{"title":"Ataxia telangiectasia","authors":"John Collyer, Deepa S Rajan","doi":"10.1016/j.spen.2024.101169","DOIUrl":"10.1016/j.spen.2024.101169","url":null,"abstract":"<div><div>Ataxia telangiectasia (AT) is a rare neurocutaneous syndrome that results from biallelic pathogenic variants in the ataxia telangiectasia mutated (<em>ATM</em>) gene, named for its characteristic cerebellar ataxia in the early toddler years and variable oculocutaneous telangiectasias in the school age years. While its name only hints at neurologic and cutaneous manifestations, this multisystemic disorder also has important immunologic, oncologic, respiratory, and endocrinologic implications. This article will review the function of the <em>ATM</em> gene, the neurologic manifestations of AT, non-neurologic complications, mimickers of AT (including other disorders of defective DNA repair), and the realm of therapeutic research for AT.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"52 ","pages":"Article 101169"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.spen.2024.101172
Manikum Moodley, Karla Robles Lopez
Neurofibromatosis type 1 (NF1) is one of the most common genetic conditions. It can be inherited in an autosomal dominant manner, but almost half of cases occur de novo. NF1 is associated with café-au-lait macules, freckles in the inguinal and axillary region, neurofibromas, Lisch nodules of the iris or choroidal abnormalities, optic pathway gliomas, and distinctive bone anomalies. It has complete penetrance but highly variable disease manifestations. Certain features including café-au-lait macules, bony abnormalities, and optic pathway gliomas emerge by early childhood, but others appear later in life. A cure for NF1 has not been found, however emerging treatments have involved modulation of the RAS/MAPK signaling pathway.
{"title":"Neurofibromatosis type 1 - an update","authors":"Manikum Moodley, Karla Robles Lopez","doi":"10.1016/j.spen.2024.101172","DOIUrl":"10.1016/j.spen.2024.101172","url":null,"abstract":"<div><div>Neurofibromatosis type 1 (NF1) is one of the most common genetic conditions. It can be inherited in an autosomal dominant manner, but almost half of cases occur <em>de novo</em>. NF1 is associated with café-au-lait macules, freckles in the inguinal and axillary region, neurofibromas, Lisch nodules of the iris or choroidal abnormalities, optic pathway gliomas, and distinctive bone anomalies. It has complete penetrance but highly variable disease manifestations. Certain features including café-au-lait macules, bony abnormalities, and optic pathway gliomas emerge by early childhood, but others appear later in life. A cure for NF1 has not been found, however emerging treatments have involved modulation of the RAS/MAPK signaling pathway.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"52 ","pages":"Article 101172"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.spen.2024.101168
Sunny Greene , Ariane Soldatos , Camilo Toro , Wadih M. Zein , Joseph Snow , Tanya J. Lehky , May Christine V. Malicdan , Wendy J. Introne
Chedíak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the Lysosomal Trafficking Regulator (LYST) gene, leading to defective lysosomal function in immune cells, melanocytes, and neurons. Clinically, CHS is characterized by a spectrum of symptoms, including immunodeficiency, partial oculocutaneous albinism, bleeding tendencies, neurodevelopmental deficits and progressive neurodegenerative symptoms.
The severity of CHS correlates with the type of LYST mutation: the classic form, linked to nonsense or frameshift mutations, presents early in childhood with severe immune dysfunction, recurrent infections, and a high risk of hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory state. Without timely treatment, including hematopoietic stem cell transplantation (HSCT), prognosis is poor, with high mortality in early life. Atypical forms, associated with missense mutations, manifest later with milder immunologic symptoms but inevitably progress to neurological impairment, including cognitive decline and motor dysfunction. Diagnosing CHS is complex due to its rarity, phenotypic variability, and overlap with other disorders. A thorough approach, incorporating clinical evaluation, peripheral blood smear for giant granules in leukocytes, and genetic testing for LYST mutations, is crucial for accurate diagnosis.
Management of CHS requires a multidisciplinary approach, focusing on HSCT for immunologic and hematologic stabilization and symptomatic and supportive care for neurological symptoms. Even those patients who undergo stabilizing HSCT eventually develop neurological difficulties. This review provides an in-depth exploration of CHS, covering its epidemiology, clinical presentation, molecular genetics, diagnostic challenges, and current management strategies, while emphasizing the necessity of a comprehensive, multidisciplinary approach to improve patient outcomes.
{"title":"Chedíak-Higashi Syndrome: Hair-to-toe spectrum","authors":"Sunny Greene , Ariane Soldatos , Camilo Toro , Wadih M. Zein , Joseph Snow , Tanya J. Lehky , May Christine V. Malicdan , Wendy J. Introne","doi":"10.1016/j.spen.2024.101168","DOIUrl":"10.1016/j.spen.2024.101168","url":null,"abstract":"<div><div>Chedíak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the Lysosomal Trafficking Regulator (<em>LYST</em>) gene, leading to defective lysosomal function in immune cells, melanocytes, and neurons. Clinically, CHS is characterized by a spectrum of symptoms, including immunodeficiency, partial oculocutaneous albinism, bleeding tendencies, neurodevelopmental deficits and progressive neurodegenerative symptoms.</div><div>The severity of CHS correlates with the type of <em>LYST</em> mutation: the classic form, linked to nonsense or frameshift mutations, presents early in childhood with severe immune dysfunction, recurrent infections, and a high risk of hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory state. Without timely treatment, including hematopoietic stem cell transplantation (HSCT), prognosis is poor, with high mortality in early life. Atypical forms, associated with missense mutations, manifest later with milder immunologic symptoms but inevitably progress to neurological impairment, including cognitive decline and motor dysfunction. Diagnosing CHS is complex due to its rarity, phenotypic variability, and overlap with other disorders. A thorough approach, incorporating clinical evaluation, peripheral blood smear for giant granules in leukocytes, and genetic testing for <em>LYST</em> mutations, is crucial for accurate diagnosis.</div><div>Management of CHS requires a multidisciplinary approach, focusing on HSCT for immunologic and hematologic stabilization and symptomatic and supportive care for neurological symptoms. Even those patients who undergo stabilizing HSCT eventually develop neurological difficulties. This review provides an in-depth exploration of CHS, covering its epidemiology, clinical presentation, molecular genetics, diagnostic challenges, and current management strategies, while emphasizing the necessity of a comprehensive, multidisciplinary approach to improve patient outcomes.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"52 ","pages":"Article 101168"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.spen.2024.101170
Chelsey Ortman, Leah Ferrante
{"title":"Neurocutaneous Disorders of Childhood and Adolescence: Towards Earlier Diagnosis and Improved Treatment","authors":"Chelsey Ortman, Leah Ferrante","doi":"10.1016/j.spen.2024.101170","DOIUrl":"10.1016/j.spen.2024.101170","url":null,"abstract":"","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"52 ","pages":"Article 101170"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.spen.2024.101167
Chelsey Ortman , Elissa Ortolani
Clinical manifestations of hereditary hemorrhagic telangiectasia (HHT) include vascular malformations of the skin, nasal mucosa, gastrointestinal tract, lungs, liver and central nervous system. These malformations range from punctate telangiectasias to larger arteriovenous malformations within visceral organs and the central nervous system. Vascular malformations increase risk for acute and chronic bleeding, anemia, as well secondary complications related to arterial-venous shunting. Diagnosis can be made with the Curaçao criteria, which includes the presence of epistaxis, telangiectasias, arteriovenous malformations, and first-degree family member with HHT. Nearly all patients with HHT will have a pathogenic variant in the ENG or ACVRL1 genes, while a smaller number will have a variant in SMAD4 or no clear genetic etiology. While there is no cure for HHT, medical management of vascular complications may include oral tranexamic acid and IV bevacizumab. Endovascular and surgical treatments are clinically indicated when the benefits outweigh the risks of the interventions.
{"title":"Hereditary hemorrhagic telangiectasia: A pediatric-focused review","authors":"Chelsey Ortman , Elissa Ortolani","doi":"10.1016/j.spen.2024.101167","DOIUrl":"10.1016/j.spen.2024.101167","url":null,"abstract":"<div><div>Clinical manifestations of hereditary hemorrhagic telangiectasia (HHT) include vascular malformations of the skin, nasal mucosa, gastrointestinal tract, lungs, liver and central nervous system. These malformations range from punctate telangiectasias to larger arteriovenous malformations within visceral organs and the central nervous system. Vascular malformations increase risk for acute and chronic bleeding, anemia, as well secondary complications related to arterial-venous shunting. Diagnosis can be made with the Curaçao criteria, which includes the presence of epistaxis, telangiectasias, arteriovenous malformations, and first-degree family member with HHT. Nearly all patients with HHT will have a pathogenic variant in the ENG or ACVRL1 genes, while a smaller number will have a variant in SMAD4 or no clear genetic etiology. While there is no cure for HHT, medical management of vascular complications may include oral tranexamic acid and IV bevacizumab. Endovascular and surgical treatments are clinically indicated when the benefits outweigh the risks of the interventions.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"52 ","pages":"Article 101167"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.spen.2024.101171
Manikum Moodley, Chelsey Ortman
Neurofibromatosis type 2-related schwannomatosis (NF2-SWN) is an autosomal dominant inherited disorder with 100 % penetrance associated with pathogenic variants of the NF2 gene on the long arm of chromosome 22. It was previously known as central neurofibromatosis and neurofibromatosis type 2. NF2-SWN has a global incidence of about 1 in 50,000. This disorder is characterized by the formation of multiple types of central nervous system tumors. While bilateral vestibular schwannomas affect more than 95 % of individuals with NF2-SWN, meningiomas, ependymomas, gliomas, other schwannomas, and ophthalmologic abnormalities are also common. Careful dermatologic, ophthalmologic, and neurologic examination can identify signs of NF2-SWN to allow timely initiation of disease specific treatment. Most patients benefit from multimodal treatment, including surgery.
{"title":"Neurofibromatosis type 2-related schwannomatosis - An update","authors":"Manikum Moodley, Chelsey Ortman","doi":"10.1016/j.spen.2024.101171","DOIUrl":"10.1016/j.spen.2024.101171","url":null,"abstract":"<div><div>Neurofibromatosis type 2-related schwannomatosis (NF2-SWN) is an autosomal dominant inherited disorder with 100 % penetrance associated with pathogenic variants of the <em>NF2</em> gene on the long arm of chromosome 22. It was previously known as central neurofibromatosis and neurofibromatosis type 2. NF2-SWN has a global incidence of about 1 in 50,000. This disorder is characterized by the formation of multiple types of central nervous system tumors. While bilateral vestibular schwannomas affect more than 95 % of individuals with NF2-SWN, meningiomas, ependymomas, gliomas, other schwannomas, and ophthalmologic abnormalities are also common. Careful dermatologic, ophthalmologic, and neurologic examination can identify signs of NF2-SWN to allow timely initiation of disease specific treatment. Most patients benefit from multimodal treatment, including surgery.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"52 ","pages":"Article 101171"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.spen.2024.101166
Fabiana Castro Porto Silva Lopes, Camryn Schroeder, Bhairav Patel, Moise L. Levy
Encephalocraniocutaneous lipomatosis (ECCL), also known as Haberland syndrome, is a sporadic tumor predisposition neurocutaneous disorder, included in the oculoectodermal syndrome group of mosaic RASopathies. ECCL primarily affects the skin, central nervous system and eyes. Key diagnostic features include nevus psiloliparus, a hallmark subcutaneous lipomatous hamartoma associated with alopecia, along with subcutaneous lipomas, focal skin aplasia, and patchy alopecia. Neurologically, intracranial lipomas, particularly in the cerebellopontine angle, are prevalent, along with cortical dysplasia, ventriculomegaly, and vascular malformations. Ocular findings commonly involve choristomas, lipodermoids, and dermoids, which may impair vision. Diagnosis can be made clinically, but further confirmatory genetic testing can in some cases identify a pathogenic variant in the FGFR1 or KRAS genes. Molecular testing aids diagnosis but is not always conclusive.
Management is multidisciplinary with focus on symptomatic management, typically involving dermatological, neurological, and ophthalmologic evaluations with consideration of brain and spine neuroimaging and surgical management of tumors. The prognosis varies, with most individuals leading generally normal lives, though there is a risk of developmental delay, seizures, and low-grade gliomas. The severity of CNS involvement does not consistently correlate with cutaneous or ocular abnormalities.
{"title":"Review of encephalocraniocutaneous lipomatosis","authors":"Fabiana Castro Porto Silva Lopes, Camryn Schroeder, Bhairav Patel, Moise L. Levy","doi":"10.1016/j.spen.2024.101166","DOIUrl":"10.1016/j.spen.2024.101166","url":null,"abstract":"<div><div>Encephalocraniocutaneous lipomatosis (ECCL), also known as Haberland syndrome, is a sporadic tumor predisposition neurocutaneous disorder, included in the oculoectodermal syndrome group of mosaic RASopathies. ECCL primarily affects the skin, central nervous system and eyes. Key diagnostic features include nevus psiloliparus, a hallmark subcutaneous lipomatous hamartoma associated with alopecia, along with subcutaneous lipomas, focal skin aplasia, and patchy alopecia. Neurologically, intracranial lipomas, particularly in the cerebellopontine angle, are prevalent, along with cortical dysplasia, ventriculomegaly, and vascular malformations. Ocular findings commonly involve choristomas, lipodermoids, and dermoids, which may impair vision. Diagnosis can be made clinically, but further confirmatory genetic testing can in some cases identify a pathogenic variant in the FGFR1 or KRAS genes. Molecular testing aids diagnosis but is not always conclusive.</div><div>Management is multidisciplinary with focus on symptomatic management, typically involving dermatological, neurological, and ophthalmologic evaluations with consideration of brain and spine neuroimaging and surgical management of tumors. The prognosis varies, with most individuals leading generally normal lives, though there is a risk of developmental delay, seizures, and low-grade gliomas. The severity of CNS involvement does not consistently correlate with cutaneous or ocular abnormalities.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"52 ","pages":"Article 101166"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.spen.2024.101150
Leah Ferrante , Chelsey Ortman
A detailed understanding of genetics is critical to the diagnosis, management, and prognostication of neurocutaneous disorders. Inheritance patterns can provide a key to the identification of different neurocutaneous disorders. Autosomal dominant disorders, like neurofibromatosis type 1 and tuberous sclerosis complex, affect males and females equally and are typically seen in every generation of a pedigree due to pathogenic changes to one copy of a gene on a somatic chromosome. Autosomal recessive disorders, such as ataxia-telangiectasia, affect males and females equally but typically skip generations on pedigrees as there needs to be a pathogenic variant of the gene on each of the pair of somatic chromosomes. X-linked disorders such as incontinentia pigmenti and Fabry disease primarily affect males or affect them more severely, but in the case of incontinentia pigmenti, the condition is lethal in males and only females are noted to be affected. The pathogenic variant that is disease causing is on the X sex chromosome, of which females have two and males have one. Somatic mosaic disorders like Sturge Weber syndrome are due to pathogenic variants only in a subset of cells post-fertilization and are not present in gametes, and so are not passed on to the next generation. Conditions that are a result of germline mosaicism are usually identified as autosomal dominant conditions that have not been present in the family prior to a single child being affected, with suspicion strengthening if siblings are diagnosed with the same condition. Regardless of the suspected inheritance pattern, it is essential to consider the ethical implications of genetic testing, including family planning, discovery of consanguinity, disclosure to other potentially affected family members, and diagnostic uncertainty.
详细了解遗传学对于神经皮肤疾病的诊断、管理和预后至关重要。遗传模式是鉴别不同神经皮肤疾病的关键。常染色体显性遗传疾病，如神经纤维瘤病 1 型和结节性硬化症复合体，对男性和女性的影响相同，通常由于体细胞染色体上的一个基因拷贝发生了致病性变化而在血统中的每一代都会出现。常染色体隐性遗传病，如共济失调-特朗吉斯症，对男性和女性的影响相同，但由于每对体细胞染色体上的基因都需要有一个致病变体，因此通常会在血统中跳一代。猪失禁症和法布里病等 X 连锁疾病主要影响男性，或对男性的影响更为严重，但在猪失禁症中，男性患上这种疾病是致命的，只有女性才会受到影响。致病变体位于 X 性染色体上，其中女性有两条，男性有一条。像 Sturge Weber 综合征这样的体细胞镶嵌性疾病是由于受精后的一部分细胞中存在致病变体，配子中不存在这种变体，因此不会遗传给下一代。种系镶嵌导致的疾病通常被认定为常染色体显性遗传病，在单个孩子患病之前，家族中并不存在这种疾病，如果兄弟姐妹被诊断出患有相同的疾病，则会加强怀疑。无论怀疑的遗传模式是什么，都必须考虑基因检测的伦理影响，包括家庭计划、近亲关系的发现、向其他可能受影响的家庭成员披露以及诊断的不确定性。
{"title":"Genetic principles related to neurocutaneous disorders","authors":"Leah Ferrante , Chelsey Ortman","doi":"10.1016/j.spen.2024.101150","DOIUrl":"10.1016/j.spen.2024.101150","url":null,"abstract":"<div><div>A detailed understanding of genetics is critical to the diagnosis, management, and prognostication of neurocutaneous disorders. Inheritance patterns can provide a key to the identification of different neurocutaneous disorders. Autosomal dominant disorders, like neurofibromatosis type 1 and tuberous sclerosis complex, affect males and females equally and are typically seen in every generation of a pedigree due to pathogenic changes to one copy of a gene on a somatic chromosome. Autosomal recessive disorders, such as ataxia-telangiectasia, affect males and females equally but typically skip generations on pedigrees as there needs to be a pathogenic variant of the gene on each of the pair of somatic chromosomes. X-linked disorders such as incontinentia pigmenti and Fabry disease primarily affect males or affect them more severely, but in the case of incontinentia pigmenti, the condition is lethal in males and only females are noted to be affected. The pathogenic variant that is disease causing is on the X sex chromosome, of which females have two and males have one. Somatic mosaic disorders like Sturge Weber syndrome are due to pathogenic variants only in a subset of cells post-fertilization and are not present in gametes, and so are not passed on to the next generation. Conditions that are a result of germline mosaicism are usually identified as autosomal dominant conditions that have not been present in the family prior to a single child being affected, with suspicion strengthening if siblings are diagnosed with the same condition. Regardless of the suspected inheritance pattern, it is essential to consider the ethical implications of genetic testing, including family planning, discovery of consanguinity, disclosure to other potentially affected family members, and diagnostic uncertainty.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"51 ","pages":"Article 101150"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.spen.2024.101156
Tena Rosser
Incontinentia pigmenti (IP) is a rare X-linked dominant, multi-system genetic disorder characterized by evolving skin lesions that occurs almost exclusively in females. Additional manifestations most often involve embryologically-derived ectodermal tissues including the central nervous system (CNS), eyes, hair, teeth and nails. IP is associated with a wide range of neurologic abnormalities, several of which can be associated with significant morbidity. In the neonatal period, while the pathophysiology is poorly understood, inflammatory microvascular changes can lead to ischemic strokes in non-vascular territories and acute disseminated encephalomyelitis, resulting in serious chronic neurologic sequelae such as epilepsy, cerebral palsy and intellectual disability. Additional neuroimaging findings may include periventricular and subcortical white matter abnormalities and cerebral as well as cerebellar dysgenesis. Advancements over time have allowed for improved phenotyping, identification of the causative IKBKG pathogenic variant, creation and refinement of clinical diagnostic criteria and the development of management guidelines which promote multi-disciplinary care. Due to frequent CNS involvement, neurologists play a critical role in the treatment of individuals with IP throughout the lifespan.
猪软化症（Incontinentia pigmenti，IP）是一种罕见的 X 连锁显性、多系统遗传性疾病，其特征是不断发展的皮肤病变，几乎只发生在女性身上。其他表现通常涉及胚胎衍生的外胚层组织，包括中枢神经系统（CNS）、眼睛、头发、牙齿和指甲。IP 与多种神经系统异常有关，其中有几种可能与严重的发病率有关。在新生儿期，虽然病理生理学尚不清楚，但炎症性微血管病变可导致非血管区域缺血性中风和急性播散性脑脊髓炎，造成严重的慢性神经系统后遗症，如癫痫、脑瘫和智力障碍。其他神经影像学检查结果可能包括脑室周围和皮层下白质异常、大脑和小脑发育不良。随着时间的推移，表型的改进、IKBKG 致病变体的鉴定、临床诊断标准的建立和完善以及促进多学科治疗的管理指南的制定都取得了进展。由于 IP 常累及中枢神经系统，神经科医生在 IP 患者的整个生命周期的治疗中都扮演着至关重要的角色。
{"title":"Incontinentia pigmenti","authors":"Tena Rosser","doi":"10.1016/j.spen.2024.101156","DOIUrl":"10.1016/j.spen.2024.101156","url":null,"abstract":"<div><div>Incontinentia pigmenti (IP) is a rare X-linked dominant, multi-system genetic disorder characterized by evolving skin lesions that occurs almost exclusively in females. Additional manifestations most often involve embryologically-derived ectodermal tissues including the central nervous system (CNS), eyes, hair, teeth and nails. IP is associated with a wide range of neurologic abnormalities, several of which can be associated with significant morbidity. In the neonatal period, while the pathophysiology is poorly understood, inflammatory microvascular changes can lead to ischemic strokes in non-vascular territories and acute disseminated encephalomyelitis, resulting in serious chronic neurologic sequelae such as epilepsy, cerebral palsy and intellectual disability. Additional neuroimaging findings may include periventricular and subcortical white matter abnormalities and cerebral as well as cerebellar dysgenesis. Advancements over time have allowed for improved phenotyping, identification of the causative <em>IKBKG</em> pathogenic variant, creation and refinement of clinical diagnostic criteria and the development of management guidelines which promote multi-disciplinary care. Due to frequent CNS involvement, neurologists play a critical role in the treatment of individuals with IP throughout the lifespan.</div></div>","PeriodicalId":49284,"journal":{"name":"Seminars in Pediatric Neurology","volume":"51 ","pages":"Article 101156"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.spen.2024.101155
Kristen H. Arredondo, Kristina Jülich, E. Steve Roach
Tuberous sclerosis complex (TSC) is a rare neurocutaneous disorder of mTOR pathway dysregulation resulting from pathogenic variants in the TSC1 or TSC2 genes. Expression of this disorder may involve abnormal tissue growth and dysfunction within the brain, kidneys, heart, lungs, eyes, skin, bones, and teeth. Neurological manifestations can include subependymal giant cell astrocytomas (SEGAs), high rates of infantile spasms, drug-resistant epilepsy, developmental delay, cognitive impairment, autism spectrum disorder, and other neurobehavioral manifestations. Here we review the potential clinical manifestations of TSC by system, recommended diagnostic and surveillance testing, genetic testing, currently available therapeutic options, and considerations for education and social support resources given the unique challenges of this multi-system disorder.
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