Prenatal Diagnosis of Poretti-Boltshauser Syndrome: A Case of Live Birth with Confirmed LAMA1 Variants

Prenatal Diagnosis of Poretti-Boltshauser Syndrome: A Case of Live Birth with Confirmed LAMA1 Variants | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Prenatal Diagnosis of Poretti-Boltshauser Syndrome: A Case of Live Birth with Confirmed LAMA1 Variants Ismail Yilmaz, Gorkem Arica, Beyhan Tuysuz, Ayse Kalyoncu Ucar, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9107536/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Introduction: Poretti-Boltshauser syndrome (PBS; OMIM #615960) is a rare autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in the LAMA1 gene. It is characterized by cerebellar dysplasia with cyst formation, inferior vermian hypoplasia, and progressive visual impairment. Case presentation: Inferior vermian hypoplasia and right renal agenesis detected at 20 weeks' gestation on ultrasonography. Amniocentesis revealed a normal karyotype and chromosomal microarray. Trio whole-exome sequencing identified compound heterozygous LAMA1 variants. Parental segregation confirmed biallelic inheritance, establishing the diagnosis of PBS. A male infant was born at 38 weeks and 4 days. Postnatal evaluation showed bilateral cerebellar cortical irregularities with millimetric cysts on brain MRI, severe macular atrophy with punch-hole foveal lesions, global developmental delay, generalized hypotonia, and profound visual impairment. Conclusion This case expands the prenatal phenotype of PBS and highlights the diagnostic value of integrating advanced fetal imaging with trio whole-exome sequencing in fetuses presenting with posterior fossa abnormalities. cerebellar dysplasia LAMA1 posterior fossa abnormalities Poretti-Boltshauser syndrome prenatal diagnosis whole-exome sequencing Figures Figure 1 Introduction Poretti-Boltshauser syndrome (PBS; OMIM #615960) is a rare autosomal recessive neurodevelopmental disorder characterized by cerebellar dysplasia with cyst formation, inferior vermian hypoplasia, and progressive visual impairment [ 1 ]. The condition results from biallelic pathogenic variants in the LAMA1 gene (chromosome 18p11.31), which encodes laminin subunit alpha-1, a critical extracellular matrix component essential for basement membrane stability within the cerebellar cortex and retina [ 1 ]. PBS is exceedingly rare; approximately 41 cases were reported between 2014 and 2022 [ 2 ]. Prenatal diagnosis of PBS remains challenging due to overlapping imaging features with other posterior fossa malformations. To date, only one prenatally diagnosed case with molecular confirmation has been reported, which resulted in pregnancy termination [ 3 ]. The natural history and postnatal outcomes of prenatally diagnosed PBS therefore remain poorly characterized. We present the first case of a live birth following prenatal molecular diagnosis of PBS with confirmed pathogenic LAMA1 variants. Case Presentation The mother was a 28-year-old gravida 2, para 1 woman. The couple was healthy and nonconsanguineous. The family and obstetric history was not indicative. Hypoplastic cerebellar vermis measuring below the 5th percentile, inferior vermian hypoplasia and right renal agenesis were identified at 20 weeks' gestation by ultrasonography (Fig. 1 a). Mild hypoplasia of the inferior cerebellar vermis was demonstrated by ultrasonographic follow-up at 28, 32, and 37 weeks’ gestation (Fig. 1 b). Fetal magnetic resonance imaging (MRI) performed at 25 weeks' and 32 weeks' gestation demonstrated marked hypoplasia of the inferior cerebellar vermis (Fig. 1 c). Amniocentesis was performed at 21 weeks' gestation. Conventional karyotype and chromosomal microarray analysis (CMA) were initially performed. Following the return of cytogenetic testing results, trio whole exome sequencing (WES) was performed using the Illumina NovaSeq 6000 sequencer. Sanger sequencing was used for confirmatory testing. Cytogenetic testing analysis revealed a normal 46, XY karyotype with no pathogenic copy number variants on CMA. Subsequent WES analysis demonstrated compound heterozygous variants in the LAMA1 (laminin1) gene (chromosome 18p11.31): c.505C > T (p.Arg169Ter), classified as pathogenic, and c.8095-3C > G, classified as a variant of uncertain significance. All identified variants were checked for nomenclature accuracy via Variant Validator [ 4 ]. Parental segregation analysis confirmed heterozygous carrier status in both parents consistent with Poretti-Boltshauser syndrome (PBS). Following comprehensive multidisciplinary counseling regarding the diagnosis, prognosis, and potential outcomes, the family elected to continue the pregnancy. The male infant was born at 38w4d with a birth weight of 3440 gram. Apgar score was 9 at 5 minutes. Neonatal evaluation confirmed right renal agenesis on ultrasound. Ophthalmologic examination revealed severe macular atrophy with complete loss of retinal tissue in the macular region, and characteristic "punch-hole" foveal lesions, consistent with LAMA1-related retinopathy. Neonatal brain MRI at 9 months demonstrated bilateral cerebellar hemispheric cortical irregularities with multiple millimetric cysts. Neurological assessment at 1 year of age, revealed global developmental delay, severe hypotonia, and profound visual impairment, and remains under multidisciplinary care. Discussion To the best of our knowledge, this is the first reported case of a live birth following prenatal molecular diagnosis of PBS with confirmed pathogenic LAMA1 variants. The case is also notable as the first prenatally diagnosed PBS to demonstrate specific ultrasonographic and fetal MRI findings of inferior vermian hypoplasia characteristic of the syndrome. To our knowledge, there is one more prenatally diagnosed case detected at 22 weeks of gestation with unspecific finding of normally shaped but hyperechogenic cerebellum and terminated the pregnancy after the molecular diagnosis [ 4 ]. Three additional cases had postnatally diagnosed PBS with mild ventriculomegaly detected on prenatal ultrasound [ 2 , 5 , 6 ]. MRI of the brain mainly shows cerebellar dysplasia, hypoplasia of the cerebellar vermis, and cerebellar cysts that can vary in size, quantity, and location in PBS [ 2 ]. However, these are postnatal findings and prenatal evolution of the cerebellum is not clear. In the present case, bilateral cerebellar hemispheric cortical irregularities with multiple millimetric cyst demonstrated by postnatal MRI were not identified in-utero. The inferior cerebellar vermis appeared hypoplastic from 20 weeks of gestation, and this finding persisted during pregnancy and the postnatal period. These observations suggest that particular postnatal findings, such as a dysplastic cerebellar vermis, may be detectable prenatally. In conclusion, present case expands the features of the prenatal phenotype of PBS and highlights the importance of WES in fetuses presenting with posterior fossa abnormalities. Declarations Author Contributions CRediT: Ismail Yilmaz: Data curation, Formal analysis, Investigation, Writing – original draft; Riza Madazli: Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – original draft; Gorkem Arica: Data curation, Visualization, Writing – review & editing; Beyhan Tuysuz: Data curation, Formal analysis; Ayse Kalyoncu Ucar: Data curation, Visualization Disclosure statement No potential conflict of interest was reported by the authors. Informed consent statement Written informed consent was obtained from the parents for publication of this case report and accompanying images. Institutional review board statement Our investigations were carried out following the rules of the Declaration of Helsinki of 1975, revised in 2013. Funding The author(s) reported there is no funding associated with the work featured in this article. Data availability statement The data presented in this study are available on request from the corresponding author. References Alsahlawi Z, Barni AM, Barni BM, Abbod H, Kadhem F, Al Harmi H. Poretti-Boltshauser Syndrome: A Report of Two Cases From Bahrain With a Novel Mutation and Literature Review. Cureus. 2025;17(1):e77172. 10.7759/cureus.7717 . Geerts C, Sznajer Y, D'haenens E, Dumitriu D, Nassogne MC. Phenotypic spectrum of patients with Poretti-Boltshauser syndrome: patient report of antenatal ventriculomegaly and esophageal atresia. Eur J Med Genet. 2023;66:104692. Pereira-Macedo M, Grangeia A, Braga AC, Rolim R, Matias A. Prenatal Diagnosis of Poretti-Boltshauser Syndrome – a Case Report of a Molar Tooth Sign Mimic. Cerebellum. 2024;23(6):2646–9. Freeman PJ, Hart RK, Gretton LJ, Brookes AJ, Dalgleish R, VariantValidator. Accurate validation, mapping, and formatting of sequence variation descriptions. Hum Mutat. 2018;39(1):61–8. 10.1002/humu.23348 . Kamate M, Goudar N, Hattiholi V. Antenatal presentation and supratentorial brain abnormalities in a child with Poretti-Boltshauser syndrome. Brain Dev. 2022;44:139–41. Chen M, Zhang M, Qian Y, Yang Y, Sun Y, Liu B, Wang L, Dong M. Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping. Npj Genomic Med. 2020;5:1. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Apr, 2026 Reviews received at journal 30 Mar, 2026 Reviewers agreed at journal 26 Mar, 2026 Reviewers invited by journal 24 Mar, 2026 Editor assigned by journal 24 Mar, 2026 Submission checks completed at journal 24 Mar, 2026 First submitted to journal 12 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9107536","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":611598862,"identity":"84161d05-cd25-48b4-b6dd-ff680e9dea34","order_by":0,"name":"Ismail Yilmaz","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"prefix":"","firstName":"Ismail","middleName":"","lastName":"Yilmaz","suffix":""},{"id":611598863,"identity":"5e4c29ef-b8ef-449c-b324-dff17c8c25a1","order_by":1,"name":"Gorkem Arica","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"prefix":"","firstName":"Gorkem","middleName":"","lastName":"Arica","suffix":""},{"id":611598864,"identity":"440bb40c-153f-42c3-a01e-f23b4f5acdab","order_by":2,"name":"Beyhan Tuysuz","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"prefix":"","firstName":"Beyhan","middleName":"","lastName":"Tuysuz","suffix":""},{"id":611598865,"identity":"4b6b9da3-650d-469c-a3a1-0ef9b291c025","order_by":3,"name":"Ayse Kalyoncu Ucar","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"prefix":"","firstName":"Ayse","middleName":"Kalyoncu","lastName":"Ucar","suffix":""},{"id":611598866,"identity":"e79a7b41-e99e-4daa-8174-6934b55202ef","order_by":4,"name":"Riza Madazli","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYHACAwaGAgkGfhAzoYBoLQYSDJINIC0GxGsBogNQNkGg235448cfBhb5xudXJ354YMAgzy92AL8WszNpxRISBhKW22683SwBdJjhzNkJBLQcyDGQMAAisxtnN4C0JBjcJqTl/BvjHwlALcYzzm7+QZyWGzlmEgdAFvH3biPSlhvPyiwbgFokbvBuswBaR4Rfzidvvvmjos6Av/8siGEjzy9NQAsCSIBVShCrHAT4D5CiehSMglEwCkYSAABuv0JhPmis3AAAAABJRU5ErkJggg==","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":true,"prefix":"","firstName":"Riza","middleName":"","lastName":"Madazli","suffix":""}],"badges":[],"createdAt":"2026-03-12 18:08:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9107536/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9107536/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105548146,"identity":"898bef9d-7fa9-4a88-8bd7-6a58e75035d3","added_by":"auto","created_at":"2026-03-27 09:28:14","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":357080,"visible":true,"origin":"","legend":"\u003cp\u003eFetal neuroimaging findings. (a) Midsagittal ultrasonographic view at 20 weeks of gestation demonstrating inferior vermian hypoplasia. (b) Follow-up ultrasonography at 27 weeks confirming persistence of inferior vermian hypoplasia. (c) Fetal brain MRI at 32 weeks demonstrating marked hypoplasia of the inferior cerebellar vermis.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9107536/v1/222477029befa1bec11c088b.jpeg"},{"id":105567362,"identity":"603aa372-123b-42b0-9c4b-a1657582be45","added_by":"auto","created_at":"2026-03-27 12:59:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":672028,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9107536/v1/8da43f91-76de-4fc5-8f99-352f9b54cac5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prenatal Diagnosis of Poretti-Boltshauser Syndrome: A Case of Live Birth with Confirmed LAMA1 Variants","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePoretti-Boltshauser syndrome (PBS; OMIM #615960) is a rare autosomal recessive neurodevelopmental disorder characterized by cerebellar dysplasia with cyst formation, inferior vermian hypoplasia, and progressive visual impairment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The condition results from biallelic pathogenic variants in the LAMA1 gene (chromosome 18p11.31), which encodes laminin subunit alpha-1, a critical extracellular matrix component essential for basement membrane stability within the cerebellar cortex and retina [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. PBS is exceedingly rare; approximately 41 cases were reported between 2014 and 2022 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrenatal diagnosis of PBS remains challenging due to overlapping imaging features with other posterior fossa malformations. To date, only one prenatally diagnosed case with molecular confirmation has been reported, which resulted in pregnancy termination [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The natural history and postnatal outcomes of prenatally diagnosed PBS therefore remain poorly characterized. We present the first case of a live birth following prenatal molecular diagnosis of PBS with confirmed pathogenic LAMA1 variants.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eThe mother was a 28-year-old gravida 2, para 1 woman. The couple was healthy and nonconsanguineous. The family and obstetric history was not indicative. Hypoplastic cerebellar vermis measuring below the 5th percentile, inferior vermian hypoplasia and right renal agenesis were identified at 20 weeks' gestation by ultrasonography (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). Mild hypoplasia of the inferior cerebellar vermis was demonstrated by ultrasonographic follow-up at 28, 32, and 37 weeks\u0026rsquo; gestation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). Fetal magnetic resonance imaging (MRI) performed at 25 weeks' and 32 weeks' gestation demonstrated marked hypoplasia of the inferior cerebellar vermis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmniocentesis was performed at 21 weeks' gestation. Conventional karyotype and chromosomal microarray analysis (CMA) were initially performed. Following the return of cytogenetic testing results, trio whole exome sequencing (WES) was performed using the Illumina NovaSeq 6000 sequencer. Sanger sequencing was used for confirmatory testing.\u003c/p\u003e \u003cp\u003eCytogenetic testing analysis revealed a normal 46, XY karyotype with no pathogenic copy number variants on CMA. Subsequent WES analysis demonstrated compound heterozygous variants in the LAMA1 (laminin1) gene (chromosome 18p11.31): c.505C\u0026thinsp;\u0026gt;\u0026thinsp;T (p.Arg169Ter), classified as pathogenic, and c.8095-3C\u0026thinsp;\u0026gt;\u0026thinsp;G, classified as a variant of uncertain significance. All identified variants were checked for nomenclature accuracy via Variant Validator [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Parental segregation analysis confirmed heterozygous carrier status in both parents consistent with Poretti-Boltshauser syndrome (PBS). Following comprehensive multidisciplinary counseling regarding the diagnosis, prognosis, and potential outcomes, the family elected to continue the pregnancy.\u003c/p\u003e \u003cp\u003eThe male infant was born at 38w4d with a birth weight of 3440 gram. Apgar score was 9 at 5 minutes. Neonatal evaluation confirmed right renal agenesis on ultrasound. Ophthalmologic examination revealed severe macular atrophy with complete loss of retinal tissue in the macular region, and characteristic \"punch-hole\" foveal lesions, consistent with LAMA1-related retinopathy. Neonatal brain MRI at 9 months demonstrated bilateral cerebellar hemispheric cortical irregularities with multiple millimetric cysts. Neurological assessment at 1 year of age, revealed global developmental delay, severe hypotonia, and profound visual impairment, and remains under multidisciplinary care.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first reported case of a live birth following prenatal molecular diagnosis of PBS with confirmed pathogenic LAMA1 variants. The case is also notable as the first prenatally diagnosed PBS to demonstrate specific ultrasonographic and fetal MRI findings of inferior vermian hypoplasia characteristic of the syndrome. To our knowledge, there is one more prenatally diagnosed case detected at 22 weeks of gestation with unspecific finding of normally shaped but hyperechogenic cerebellum and terminated the pregnancy after the molecular diagnosis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Three additional cases had postnatally diagnosed PBS with mild ventriculomegaly detected on prenatal ultrasound [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMRI of the brain mainly shows cerebellar dysplasia, hypoplasia of the cerebellar vermis, and cerebellar cysts that can vary in size, quantity, and location in PBS [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, these are postnatal findings and prenatal evolution of the cerebellum is not clear. In the present case, bilateral cerebellar hemispheric cortical irregularities with multiple millimetric cyst demonstrated by postnatal MRI were not identified in-utero. The inferior cerebellar vermis appeared hypoplastic from 20 weeks of gestation, and this finding persisted during pregnancy and the postnatal period. These observations suggest that particular postnatal findings, such as a dysplastic cerebellar vermis, may be detectable prenatally.\u003c/p\u003e \u003cp\u003eIn conclusion, present case expands the features of the prenatal phenotype of PBS and highlights the importance of WES in fetuses presenting with posterior fossa abnormalities.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCRediT: Ismail Yilmaz: Data curation, Formal analysis, Investigation, Writing \u0026ndash; original draft; Riza Madazli: Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing \u0026ndash; original draft; Gorkem Arica: Data curation, Visualization, Writing \u0026ndash; review \u0026amp; editing; Beyhan Tuysuz: Data curation, Formal analysis; Ayse Kalyoncu Ucar: Data curation, Visualization\u003cbr\u003e\u003cstrong\u003eDisclosure statement\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;No potential conflict of interest was reported by the authors.\u003cbr\u003e\u003cstrong\u003eInformed consent statement\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Written informed consent was obtained from the parents for publication of this case report and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional review board statement\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Our investigations were carried out following the rules of the Declaration of Helsinki of 1975,\u003cbr\u003e\u0026nbsp;revised in 2013.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The author(s) reported there is no funding associated with the work featured in this article.\u003cbr\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The data presented in this study are available on request from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlsahlawi Z, Barni AM, Barni BM, Abbod H, Kadhem F, Al Harmi H. Poretti-Boltshauser Syndrome: A Report of Two Cases From Bahrain With a Novel Mutation and Literature Review. Cureus. 2025;17(1):e77172. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.7717\u003c/span\u003e\u003cspan address=\"10.7759/cureus.7717\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGeerts C, Sznajer Y, D'haenens E, Dumitriu D, Nassogne MC. Phenotypic spectrum of patients with Poretti-Boltshauser syndrome: patient report of antenatal ventriculomegaly and esophageal atresia. Eur J Med Genet. 2023;66:104692.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePereira-Macedo M, Grangeia A, Braga AC, Rolim R, Matias A. Prenatal Diagnosis of Poretti-Boltshauser Syndrome \u0026ndash; a Case Report of a Molar Tooth Sign Mimic. Cerebellum. 2024;23(6):2646\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreeman PJ, Hart RK, Gretton LJ, Brookes AJ, Dalgleish R, VariantValidator. Accurate validation, mapping, and formatting of sequence variation descriptions. Hum Mutat. 2018;39(1):61\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/humu.23348\u003c/span\u003e\u003cspan address=\"10.1002/humu.23348\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamate M, Goudar N, Hattiholi V. Antenatal presentation and supratentorial brain abnormalities in a child with Poretti-Boltshauser syndrome. Brain Dev. 2022;44:139\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen M, Zhang M, Qian Y, Yang Y, Sun Y, Liu B, Wang L, Dong M. Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping. Npj Genomic Med. 2020;5:1.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"cerebellar dysplasia, LAMA1, posterior fossa abnormalities, Poretti-Boltshauser syndrome, prenatal diagnosis, whole-exome sequencing","lastPublishedDoi":"10.21203/rs.3.rs-9107536/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9107536/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003ePoretti-Boltshauser syndrome (PBS; OMIM #615960) is a rare autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in the LAMA1 gene. It is characterized by cerebellar dysplasia with cyst formation, inferior vermian hypoplasia, and progressive visual impairment.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eInferior vermian hypoplasia and right renal agenesis detected at 20 weeks' gestation on ultrasonography. Amniocentesis revealed a normal karyotype and chromosomal microarray. Trio whole-exome sequencing identified compound heterozygous LAMA1 variants. Parental segregation confirmed biallelic inheritance, establishing the diagnosis of PBS. A male infant was born at 38 weeks and 4 days. Postnatal evaluation showed bilateral cerebellar cortical irregularities with millimetric cysts on brain MRI, severe macular atrophy with punch-hole foveal lesions, global developmental delay, generalized hypotonia, and profound visual impairment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case expands the prenatal phenotype of PBS and highlights the diagnostic value of integrating advanced fetal imaging with trio whole-exome sequencing in fetuses presenting with posterior fossa abnormalities.\u003c/p\u003e","manuscriptTitle":"Prenatal Diagnosis of Poretti-Boltshauser Syndrome: A Case of Live Birth with Confirmed LAMA1 Variants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-27 09:26:32","doi":"10.21203/rs.3.rs-9107536/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-09T18:18:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-30T11:45:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239335437604509778107363235500396982349","date":"2026-03-26T13:27:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-24T20:20:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-24T11:39:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-24T11:38:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Cerebellum","date":"2026-03-12T17:59:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1d063865-55f9-4b57-aee6-dee3cbef49f8","owner":[],"postedDate":"March 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T10:10:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-27 09:26:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9107536","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9107536","identity":"rs-9107536","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}