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Etiopathogenesis is not fully clarified and a wide spectrum of phenotypic presentations is reported, ranging from extreme prenatal forms with adverse outcome, to slow progressive late\u2010onset forms. We report a fetus at 22 gestational weeks with evidence of Arthrogryposis Multiplex Congenita on ultrasound, presenting with fixed extended lower limbs and flexed upper limbs, bilateral clubfoot and absent fetal movements. A trio\u2010based prenatal Exome Sequencing was performed, disclosing a de novo heterozygous pathogenic in frame deletion (NM_015250.3: c.1636_1638delAAT; p.Asn546del) in <jats:italic>BICD2<\/jats:italic>. After pregnancy termination, quantitative analysis on NeuN immunostained spinal cord sections of the ventral horns, revealed that neuronal density was markedly reduced compared to the one of an age\u2010matched normal fetus and an age\u2010matched type\u2010I Spinal Muscular Atrophy sample, used as a comparative model. The present case, the first prenatally diagnosed and neuropathologically characterized, showed an early motor neuron loss in SMALED2B, providing further insight into the pathological basis of BICD2\u2010opathies.<\/jats:p>","DOI":"10.1002\/ajmg.a.62111","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T17:29:50Z","timestamp":1612805390000},"page":"1509-1514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fetal early motor neuron disruption and prenatal molecular diagnosis in a severe <scp>BICD2<\/scp>\u2010opathy"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0341-6461","authenticated-orcid":false,"given":"Enrica","family":"Marchionni","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-6225","authenticated-orcid":false,"given":"Emanuele","family":"Agolini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0788-1683","authenticated-orcid":false,"given":"Gioia","family":"Mastromoro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Guadagnolo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Roggini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Neuropsychiatry Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Riminucci","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Giancotti","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health and Urologic Science Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Corsi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Pizzuti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"},{"name":"Clinical Genomics Unit IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo (FG) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38577"},{"issue":"6","key":"e_1_2_10_3_1","first-page":"303","article-title":"Adenocarcinoma and atypical carcinoid: Morphological study of a gastric collision\u2010type tumour in the carcinoma\u2010carcinoid spectrum","volume":"27","author":"Corsi A.","year":"1995","journal-title":"The Italian Journal of Gastroenterology"},{"volume-title":"Neuromuscular disorders of infancy and childhood, a clinician's approach","year":"2002","author":"Crawford T. 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