Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series
Abstract Recent genetic studies have revealed that hemimegalencephaly (HME) is a multi‐system disorder associated with germline or mosaic variants within the PI3K‐mTOR‐GATOR1 signaling pathways. Patients with HME typically develop drug‐resistant epilepsy necessitating extensive evaluation, hemispher...
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Wiley
2024-12-01
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| Series: | Epilepsia Open |
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| Online Access: | https://doi.org/10.1002/epi4.13079 |
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| author | Benjamin Edmonds Jacqueline P. Ngo Aran Groves Beck Reyes Rolanda A. Gott Dennis J. Chia Hilda Mirbaha Shino Magaki Negar Khanlou Stacy L. Pineles Noriko Salamon Rachel M. Thompson Maya Newman Rajsekar R. Rajaraman Shaun A. Hussain Aria Fallah Bianca Russell Hiroki Nariai |
| author_facet | Benjamin Edmonds Jacqueline P. Ngo Aran Groves Beck Reyes Rolanda A. Gott Dennis J. Chia Hilda Mirbaha Shino Magaki Negar Khanlou Stacy L. Pineles Noriko Salamon Rachel M. Thompson Maya Newman Rajsekar R. Rajaraman Shaun A. Hussain Aria Fallah Bianca Russell Hiroki Nariai |
| author_sort | Benjamin Edmonds |
| collection | DOAJ |
| description | Abstract Recent genetic studies have revealed that hemimegalencephaly (HME) is a multi‐system disorder associated with germline or mosaic variants within the PI3K‐mTOR‐GATOR1 signaling pathways. Patients with HME typically develop drug‐resistant epilepsy necessitating extensive evaluation, hemispherectomy, and long‐term management. We describe the role of a multidisciplinary team (MDT) for the diagnosis and management of recent patients with HME at UCLA who underwent hemispherectomy. Genetic evaluation identified nine patients with the following variants: NPRL3 x2 germline, PIK3CA mosaicism x4, MTOR mosaicism x1, AKT3 mosaicism x1, unknown x1. Each patient's MDT comprised 4–9 specialties. One child with a MTOR variant had persistent epilepsy after hemispherectomy, but addition of everolimus resulted in an 80% decrease in seizure frequency. Another child with hemihypertrophy and PIK3CA mosaic variant was offered targeted PIK3CA inhibitor treatment, alpelisib, for overgrowth. A third child with germline NPRL3 variant inherited from their unaffected mother resulted in a sibling being diagnosed with the variant who later developed seizures secondary to focal cortical dysplasia. The implementation of a MDT offers essential guidance for families affected by HME, encompassing prognostication, surveillance, and therapeutic strategies. Identifying the etiology of HME can facilitate the development of targeted treatments and enable timely genetic counseling. Plain Language Summary Hemimegalencephaly (HME) is a complex brain disorder caused by genetic changes. It often leads to severe epilepsy that doesn't respond to standard treatments and frequently requires surgery. In this case series, nine patients with HME were identified and found to have genetic mutations in key growth‐regulating genes. A multidisciplinary team model was developed to facilitate patients' care. For example, one patient's seizures improved with surgery, another with a new targeted medication, and another received treatment for symptoms of overgrowth. This team approach provides comprehensive care for patients and can lead to efficient care coordination and implementation of novel therapies. |
| format | Article |
| id | doaj-art-d35657ba472749fd8726ffecc26ae400 |
| institution | OA Journals |
| issn | 2470-9239 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj-art-d35657ba472749fd8726ffecc26ae4002025-08-20T02:33:46ZengWileyEpilepsia Open2470-92392024-12-01962510251710.1002/epi4.13079Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case seriesBenjamin Edmonds0Jacqueline P. Ngo1Aran Groves2Beck Reyes3Rolanda A. Gott4Dennis J. Chia5Hilda Mirbaha6Shino Magaki7Negar Khanlou8Stacy L. Pineles9Noriko Salamon10Rachel M. Thompson11Maya Newman12Rajsekar R. Rajaraman13Shaun A. Hussain14Aria Fallah15Bianca Russell16Hiroki Nariai17Division of Pediatric Neurology, Department of Neurology University of Washington Seattle Washington USADivision of Pediatric Neurology, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADivision of Pediatric Neurology, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADivision of Pediatric Neurology, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADivision of Developmental Pediatrics, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADivision of Pediatric Endocrinology, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADivision of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine UCLA Medical Center Los Angeles California USADivision of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine UCLA Medical Center Los Angeles California USADivision of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine UCLA Medical Center Los Angeles California USADepartment of Ophthalmology, David Geffen School of Medicine UCLA Medical Center Los Angeles California USADepartment of Radiological Sciences University of California Los Angeles Los Angeles California USADepartment of Orthopedics University of California Los Angeles Los Angeles California USADivision of Pediatric Physical Medicine and Rehabilitation University of California Los Angeles Los Angeles California USADivision of Pediatric Neurology, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADivision of Pediatric Neurology, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADepartment of Neurosurgery, David Geffen School of Medicine UCLA Medical Center Los Angeles California USADivision of Clinical Genetics, Department of Human Genetics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USADivision of Pediatric Neurology, Department of Pediatrics, David Geffen School of Medicine UCLA Mattel Children's Hospital Los Angeles California USAAbstract Recent genetic studies have revealed that hemimegalencephaly (HME) is a multi‐system disorder associated with germline or mosaic variants within the PI3K‐mTOR‐GATOR1 signaling pathways. Patients with HME typically develop drug‐resistant epilepsy necessitating extensive evaluation, hemispherectomy, and long‐term management. We describe the role of a multidisciplinary team (MDT) for the diagnosis and management of recent patients with HME at UCLA who underwent hemispherectomy. Genetic evaluation identified nine patients with the following variants: NPRL3 x2 germline, PIK3CA mosaicism x4, MTOR mosaicism x1, AKT3 mosaicism x1, unknown x1. Each patient's MDT comprised 4–9 specialties. One child with a MTOR variant had persistent epilepsy after hemispherectomy, but addition of everolimus resulted in an 80% decrease in seizure frequency. Another child with hemihypertrophy and PIK3CA mosaic variant was offered targeted PIK3CA inhibitor treatment, alpelisib, for overgrowth. A third child with germline NPRL3 variant inherited from their unaffected mother resulted in a sibling being diagnosed with the variant who later developed seizures secondary to focal cortical dysplasia. The implementation of a MDT offers essential guidance for families affected by HME, encompassing prognostication, surveillance, and therapeutic strategies. Identifying the etiology of HME can facilitate the development of targeted treatments and enable timely genetic counseling. Plain Language Summary Hemimegalencephaly (HME) is a complex brain disorder caused by genetic changes. It often leads to severe epilepsy that doesn't respond to standard treatments and frequently requires surgery. In this case series, nine patients with HME were identified and found to have genetic mutations in key growth‐regulating genes. A multidisciplinary team model was developed to facilitate patients' care. For example, one patient's seizures improved with surgery, another with a new targeted medication, and another received treatment for symptoms of overgrowth. This team approach provides comprehensive care for patients and can lead to efficient care coordination and implementation of novel therapies.https://doi.org/10.1002/epi4.13079epilepsygeneticshemimegalencephaly (HME)MTORmultidisciplinary |
| spellingShingle | Benjamin Edmonds Jacqueline P. Ngo Aran Groves Beck Reyes Rolanda A. Gott Dennis J. Chia Hilda Mirbaha Shino Magaki Negar Khanlou Stacy L. Pineles Noriko Salamon Rachel M. Thompson Maya Newman Rajsekar R. Rajaraman Shaun A. Hussain Aria Fallah Bianca Russell Hiroki Nariai Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series Epilepsia Open epilepsy genetics hemimegalencephaly (HME) MTOR multidisciplinary |
| title | Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series |
| title_full | Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series |
| title_fullStr | Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series |
| title_full_unstemmed | Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series |
| title_short | Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series |
| title_sort | multi disciplinary team approach for pediatric hemimegalencephaly insights from a single institutional case series |
| topic | epilepsy genetics hemimegalencephaly (HME) MTOR multidisciplinary |
| url | https://doi.org/10.1002/epi4.13079 |
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