{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:36:52Z","timestamp":1788881812478,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report three siblings homozygous for <jats:italic>CSF1R<\/jats:italic> variant c.1969\u2009+\u2009115_1969\u2009+\u2009116del to expand the phenotype of \u201cbrain abnormalities, neurodegeneration, and dysosteosclerosis\u201d (BANDDOS) and discuss its link with \u201cadult leukoencephalopathy with axonal spheroids and pigmented glia\u201d (ALSP), caused by heterozygous <jats:italic>CSF1R<\/jats:italic> variants. We evaluated medical, radiological, and laboratory findings and reviewed the literature. Patients presented with developmental delay, therapy\u2010resistant epilepsy, dysmorphic features, and skeletal abnormalities. Secondary neurological decline occurred from 23\u2009years in sibling one and from 20\u2009years in sibling two. Brain imaging revealed multifocal white matter abnormalities and calcifications during initial disease in siblings two and three. Developmental brain anomalies, seen in all three, were most severe in sibling two. During neurological decline in siblings one and two, the leukoencephalopathy was progressive and had the MRI appearance of ALSP. Skeletal survey revealed osteosclerosis, most severe in sibling three. Blood markers, monocytes, dendritic cell subsets, and T\u2010cell proliferation capacity were normal. Literature review revealed variable initial disease and secondary neurological decline. BANDDOS presents with variable dysmorphic features, skeletal dysplasia, developmental delay, and epilepsy with on neuro\u2010imaging developmental brain anomalies, multifocal white matter abnormalities, and calcifications. Secondary neurological decline occurs with a progressive leukoencephalopathy, in line with early onset ALSP. Despite the role of CSF1R signaling in myeloid development, immune deficiency is absent. Phenotype varies within families; skeletal and neurological manifestations may be disparate.<\/jats:p>","DOI":"10.1002\/ajmg.a.63800","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T08:39:21Z","timestamp":1719477561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Leukoencephalopathy with calcifications, developmental brain abnormalities and skeletal dysplasia due to homozygosity for a hypomorphic <scp><i>CSF1R<\/i><\/scp> variant: A report of three siblings"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-6784","authenticated-orcid":false,"given":"Shanice","family":"Beerepoot","sequence":"first","affiliation":[{"name":"Department of Child Neurology Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, VU University, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan I. M. L.","family":"Verbeke","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam University Medical Centers, VU University, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Plantinga","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Nierkens","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra J. W.","family":"Pouwels","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam University Medical Centers, VU University, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole I.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, VU University, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cas","family":"Simons","sequence":"additional","affiliation":[{"name":"Centre for Population Genomics Garvan Institute of Medical Research and UNSW Sydney  Sydney Australia"},{"name":"Centre for Population Genomics Murdoch Children's Research Institute  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo S.","family":"van der Knaap","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, VU University, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"},{"name":"Department of Functional Genomics Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2017.10.060"},{"key":"e_1_2_8_3_1","unstructured":"Beerepoot S. et al.Heterozygous missense CSF1R variants hamper in vitro CD34+\u2010derived dendritic cell generation but not in vivo dendritic cell development. 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