{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:47:32Z","timestamp":1790718452832,"version":"4.1.0"},"reference-count":36,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2022,3,29]]},"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:p>Periventricular nodular heterotopia (PVNH) is an X-linked disease caused by loss-of-function variants in the filamin A (<jats:italic>FLNA<\/jats:italic>) gene. FLNA-PVNH is a heterogeneous disorder, and the phenotype is associated with neurological and non-neurological features including cardiovascular, gastrointestinal, pulmonary, haematological, cutaneous and skeletal manifestations. No clear definition of the FLNA-PVNH phenotype has been established, but the patients are predominantly females with seizures, cardiovascular manifestations, and normal intelligence or mild intellectual disability. Herein, we describe a PVNH patient diagnosed with a novel heterozygous missense variant in <jats:italic>FLNA<\/jats:italic> after an atypical presentation of deep vein thrombosis and thrombocytopenia. Clinical evaluation found hypermobility, cardiovascular and skin manifestations. Moreover, we conducted a literature review of 186 FLNA-PVNH patients to describe the phenotypic spectrum. In conclusion, our patient highlights the importance of thorough clinical evaluation to identify manifestations in this very heterogeneous disorder. The phenotypic review may guide clinicians in the assessment and follow-up of FLNA-PVNH patients.<\/jats:p>","DOI":"10.1136\/bcr-2021-247268","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T13:09:27Z","timestamp":1649768967000},"page":"e247268","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Phenotypic manifestations in <i>FLNA<\/i>-related periventricular nodular heterotopia: a case report and review of the literature"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-7459","authenticated-orcid":false,"given":"Julie","family":"Loft Nagel","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aia Elise","family":"J\u00f8nch","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina T T N","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Bygum","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,4,12]]},"reference":[{"key":"2025082708573267000_15.4.e247268.1","unstructured":"Robertson S . X-Linked Otopalatodigital Spectrum Disorders. In: Adam MP , Ardinger HH , Pagon RA , et al , eds. GeneReviews(\u00ae). Seattle (WA): University of Washington, Seattle Copyright \u00a9 1993-2021, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved, 1993."},{"key":"2025082708573267000_15.4.e247268.2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102959"},{"key":"2025082708573267000_15.4.e247268.3","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/humu.24002","article-title":"The X-linked filaminopathies: synergistic insights from clinical and molecular analysis","volume":"41","author":"Wade","year":"2020","journal-title":"Hum Mutat"},{"key":"2025082708573267000_15.4.e247268.4","doi-asserted-by":"crossref","DOI":"10.1186\/s12881-018-0655-0","article-title":"Flna mutations in surviving males presenting with connective tissue findings: two new case reports and review of the literature","volume":"19","author":"Cannaerts","year":"2018","journal-title":"BMC Med Genet"},{"key":"2025082708573267000_15.4.e247268.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80651-0"},{"key":"2025082708573267000_15.4.e247268.6","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/ajmg.a.38580","article-title":"Thoracic aortic aneurysm in patients with loss of function filamin A mutations: clinical characterization, genetics, and recommendations","volume":"176","author":"Chen","year":"2018","journal-title":"Am J Med Genet A"},{"key":"2025082708573267000_15.4.e247268.7","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300603"},{"key":"2025082708573267000_15.4.e247268.8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-365601"},{"key":"2025082708573267000_15.4.e247268.9","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ajmg.a.37491","article-title":"Novel X-linked syndrome of cardiac valvulopathy, keloid scarring, and reduced joint mobility due to filamin a substitution G1576R","volume":"170A","author":"Atwal","year":"2016","journal-title":"Am J Med Genet A"},{"key":"2025082708573267000_15.4.e247268.10","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/ajmg.a.37567","article-title":"A distinct X-linked syndrome involving joint contractures, keloids, large optic cup-to-disc ratio, and renal stones results from a filamin A (FlnA) mutation","volume":"170A","author":"Lah","year":"2016","journal-title":"Am J Med Genet A"},{"key":"2025082708573267000_15.4.e247268.11","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/ajmg.a.33110","article-title":"Novel cardiac findings in periventricular nodular heterotopia","volume":"152A","author":"Jefferies","year":"2010","journal-title":"Am J Med Genet A"},{"key":"2025082708573267000_15.4.e247268.12","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/ejhg.2012.209","article-title":"Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in filamin a","volume":"21","author":"Reinstein","year":"2013","journal-title":"Eur J Hum Genet"},{"key":"2025082708573267000_15.4.e247268.13","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl125"},{"key":"2025082708573267000_15.4.e247268.14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/humu.23355","article-title":"Differential regulation of two FlnA transcripts explains some of the phenotypic heterogeneity in the loss-of-function filaminopathies","volume":"39","author":"Jenkins","year":"2018","journal-title":"Hum Mutat"},{"key":"2025082708573267000_15.4.e247268.15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ejmg.2012.01.018","article-title":"Atypical male and female presentations of FLNA-related periventricular nodular heterotopia","volume":"55","author":"Fergelot","year":"2012","journal-title":"Eur J Med Genet"},{"key":"2025082708573267000_15.4.e247268.16","unstructured":"Chen MH , Walsh CA . FLNA-Related Periventricular Nodular Heterotopia. In: Adam MP , Ardinger HH , Pagon RA , et al , eds. GeneReviews(\u00ae). Seattle (WA): University of Washington, Seattle Copyright \u00a9 1993-2021, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved, 1993."},{"key":"2025082708573267000_15.4.e247268.17","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.braindev.2018.01.010","article-title":"A novel truncating mutation in FlnA causes periventricular nodular heterotopia, Ehlers-Danlos-like collagenopathy and macrothrombocytopenia","volume":"40","author":"Ieda","year":"2018","journal-title":"Brain Dev"},{"key":"2025082708573267000_15.4.e247268.18","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000149512.79621.DF"},{"key":"2025082708573267000_15.4.e247268.19","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.029173"},{"key":"2025082708573267000_15.4.e247268.20","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0187-y"},{"key":"2025082708573267000_15.4.e247268.21","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.149419"},{"key":"2025082708573267000_15.4.e247268.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-010-0206-y"},{"key":"2025082708573267000_15.4.e247268.23","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.162263"},{"key":"2025082708573267000_15.4.e247268.24","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-021-02128-1","article-title":"Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome","volume":"16","author":"Billon","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"2025082708573267000_15.4.e247268.25","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.ejmg.2018.10.015","article-title":"Prenatally diagnosed periventricular nodular heterotopia: further delineation of the imaging phenotype and outcome","volume":"61","author":"Deloison","year":"2018","journal-title":"Eur J Med Genet"},{"key":"2025082708573267000_15.4.e247268.26","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.resinv.2019.02.008","article-title":"Microdeletion in Xq28 with a polymorphic inversion in a patient with FLNA-associated progressive lung disease","volume":"57","author":"Yoshii","year":"2019","journal-title":"Respir Investig"},{"key":"2025082708573267000_15.4.e247268.27","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/ajmg.a.35917","article-title":"Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia","volume":"161A","author":"Kasper","year":"2013","journal-title":"Am J Med Genet A"},{"key":"2025082708573267000_15.4.e247268.28","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/brain\/118.5.1273","article-title":"Periventricular and subcortical nodular heterotopia. 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