The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD)
Allen et al. show that in utero exposure to maternal antibodies against the foetal AChR may mimic a wide range of persistent neuromuscular disorders in offspring, despite many asymptomatic mothers. Immune-based therapies during pregnancy can be preventative, while oral salbutamol is an effective tre...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2023 |
| Country: | España |
| Institution: | Fundació Sant Joan de Déu |
| Repository: | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| OAI Identifier: | oai:fsjd.fundanetsuite.com:p23475 |
| Online Access: | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23475 |
| Access Level: | Open access |
| Keyword: | myasthenia gravis arthrogryposis multiplex congenita fetal acetylcholine receptor inactivation syndrome transient neonatal myasthenia gravis congenital myopathy salbutamol |
| _version_ | 1878735825116594177 |
|---|---|
| author | Allen NM |
| author2 | O'Rahelly M Eymard B Chouchane M Hahn A Kearns G Kim DS Byun SY Nguyen CE Schara-Schmidt U Kölbel H Della Marina A Schneider-Gold C Roefke K Thieme A Van den Bergh P Avalos G Álvarez-Velasco R Natera-de Benito D Cheng MHM Chan WK Wan HS Thomas MA Borch L Lauzon J Kornblum C Reimann J Mueller A Kuntzer T Norwood F Ramdas S Jacobson LW Jie X Fernandez-Garcia MA Wraige E Lim M Lin JP Claeys KG Aktas S Oskoui M Hacohen Y Masud A Leite MI Palace J De Vivo D Vincent A Jungbluth H |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_browse | Aktas S Allen NM Avalos G Borch L Byun SY Chan WK Cheng MHM Chouchane M Claeys KG De Vivo D Della Marina A Eymard B Fernandez-Garcia MA Hacohen Y Hahn A Jacobson LW Jie X Jungbluth H Kearns G Kim DS Kornblum C Kuntzer T Kölbel H Lauzon J Leite MI Lim M Lin JP Masud A Mueller A Natera-de Benito D Nguyen CE Norwood F O'Rahelly M Oskoui M Palace J Ramdas S Reimann J Roefke K Schara-Schmidt U Schneider-Gold C Thieme A Thomas MA Van den Bergh P Vincent A Wan HS Wraige E Álvarez-Velasco R |
| author_facet | Allen NM O'Rahelly M Eymard B Chouchane M Hahn A Kearns G Kim DS Byun SY Nguyen CE Schara-Schmidt U Kölbel H Della Marina A Schneider-Gold C Roefke K Thieme A Van den Bergh P Avalos G Álvarez-Velasco R Natera-de Benito D Cheng MHM Chan WK Wan HS Thomas MA Borch L Lauzon J Kornblum C Reimann J Mueller A Kuntzer T Norwood F Ramdas S Jacobson LW Jie X Fernandez-Garcia MA Wraige E Lim M Lin JP Claeys KG Aktas S Oskoui M Hacohen Y Masud A Leite MI Palace J De Vivo D Vincent A Jungbluth H |
| author_role | author |
| collection | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| description | Allen et al. show that in utero exposure to maternal antibodies against the foetal AChR may mimic a wide range of persistent neuromuscular disorders in offspring, despite many asymptomatic mothers. Immune-based therapies during pregnancy can be preventative, while oral salbutamol is an effective treatment in offspring. In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_83fcdc2d1993bbcf337dfdf8fc3255d7 |
| institution | Fundació Sant Joan de Déu |
| instname_str | Fundació Sant Joan de Déu |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:fsjd.fundanetsuite.com:p23475 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | OXFORD UNIV PRESS |
| publisherStr | OXFORD UNIV PRESS |
| reponame_str | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| spelling | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) Allen NM O'Rahelly M Eymard B Chouchane M Hahn A Kearns G Kim DS Byun SY Nguyen CE Schara-Schmidt U Kölbel H Della Marina A Schneider-Gold C Roefke K Thieme A Van den Bergh P Avalos G Álvarez-Velasco R Natera-de Benito D Cheng MHM Chan WK Wan HS Thomas MA Borch L Lauzon J Kornblum C Reimann J Mueller A Kuntzer T Norwood F Ramdas S Jacobson LW Jie X Fernandez-Garcia MA Wraige E Lim M Lin JP Claeys KG Aktas S Oskoui M Hacohen Y Masud A Leite MI Palace J De Vivo D Vincent A Jungbluth H myasthenia gravis arthrogryposis multiplex congenita fetal acetylcholine receptor inactivation syndrome transient neonatal myasthenia gravis congenital myopathy salbutamol Allen et al. show that in utero exposure to maternal antibodies against the foetal AChR may mimic a wide range of persistent neuromuscular disorders in offspring, despite many asymptomatic mothers. Immune-based therapies during pregnancy can be preventative, while oral salbutamol is an effective treatment in offspring. In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors. OXFORD UNIV PRESS https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23475 |
| spellingShingle | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) Allen NM myasthenia gravis arthrogryposis multiplex congenita fetal acetylcholine receptor inactivation syndrome transient neonatal myasthenia gravis congenital myopathy salbutamol |
| status_str | publishedVersion |
| title | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) |
| title_full | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) |
| title_fullStr | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) |
| title_full_unstemmed | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) |
| title_short | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) |
| title_sort | The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) |
| topic | myasthenia gravis arthrogryposis multiplex congenita fetal acetylcholine receptor inactivation syndrome transient neonatal myasthenia gravis congenital myopathy salbutamol |
| topic_facet | myasthenia gravis arthrogryposis multiplex congenita fetal acetylcholine receptor inactivation syndrome transient neonatal myasthenia gravis congenital myopathy salbutamol |
| url | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23475 |