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Inherited defects in the neuromuscular junction can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous group of disorders which includes fetal akinesia deformation sequence (FADS) on the severe end of the spectrum. Here, we report two unrelated families with biallelic <jats:italic>CHRNB1<\/jats:italic> variants, and in each family, one child presented with lethal FADS. We contrast the diagnostic odysseys in the two families, one of which lasted 16\u2009years while the other, utilizing rapid exome sequencing, led to specific treatment in the first 2\u2009weeks of life. Furthermore, we note that <jats:italic>CHRNB1<\/jats:italic> variants may be under\u2010recognized because in both families, one of the variants is a single exon deletion that has been previously described but may not easily be detected in clinically available genetic testing.<\/jats:p>","DOI":"10.1002\/ajmg.a.62011","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T16:58:49Z","timestamp":1607619529000},"page":"827-835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp><i>CHRNB1<\/i><\/scp>\u2010associated congenital myasthenia syndrome: Expanding the clinical spectrum"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1357-9835","authenticated-orcid":false,"given":"Amanda S.","family":"Freed","sequence":"first","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington  Seattle Washington USA"},{"name":"Department of Genetics SCPMG  Panorama City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anisha C.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Neurology University of Washington  Seattle Washington USA"},{"name":"General &amp; Neuromuscular Pediatric Neurology Mary Bridge Children's Hospital  Tacoma Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna K.","family":"Brei","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics University of Washington  Seattle Washington USA"},{"name":"Department of Neonatology Children's Hospital &amp; Medical Center  Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah V.","family":"Clowes Candadai","sequence":"additional","affiliation":[{"name":"Department of Laboratories Seattle Children's Hospital  Seattle Washington USA"},{"name":"Patient\u2010Centered Laboratory Utilization Guidance Services (PLUGS) Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Thies","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean K.","family":"Mah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Neurology, Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpi","family":"Chabra","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Neurology University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Neuromuscular Neurology, Department of Neurology University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-5467","authenticated-orcid":false,"given":"A. Micheil","family":"Innes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Pediatrics, Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2843-5594","authenticated-orcid":false,"given":"James T.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington  Seattle Washington USA"},{"name":"Department of Neonatology Children's Hospital &amp; Medical Center  Omaha Nebraska USA"},{"name":"Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute  Seattle Washington USA"},{"name":"Brotman Baty Institute for Precision Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118777329.ch118"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0690-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2012.01.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00037-5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70201-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4011"},{"issue":"20","key":"e_1_2_9_10_1","first-page":"30721","article-title":"The impact of rapid exome sequencing on medical management of critically ill children","volume":"0022","author":"Freed A. 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