{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:02:02Z","timestamp":1780639322961,"version":"3.54.1"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Diagnostic anchoring to a presumed infectious etiology may delay recognition of underlying genetic disorders in children with neurodevelopmental impairment. Case presentation: A case of a child with sensorineural hearing loss, visual impairment, and developmental delay is reported; cytomegalovirus (CMV) infection was identified at 6 months of age based on positive serology and detection of viral DNA in serum and urine. Given the timing of testing, congenital CMV infection (cCMV) could not be definitively confirmed. Antiviral therapy with valganciclovir was administered. Despite antiviral treatment, severe neurodevelopmental impairment and hearing loss persisted, associated with facial dysmorphism, bilateral cryptorchidism, pectus excavatum, and optic nerve hypoplasia, findings not fully attributable to CMV infection. Brain magnetic resonance imaging (MRI) showed nonspecific findings. Chromosomal microarray analysis (CMA) performed at 4.5 years of age identified a heterozygous 908 kb de novo microdeletion at 19p13.2p13.13 containing NFIX (MIM *164005) and other morbid genes. The de novo variant was confirmed by parental testing, and the unifying genetic diagnosis of NFIX-related Malan syndrome (MIM#614753) was established. Conclusions: This case emphasizes the importance of reconsidering the initial diagnosis when the clinical phenotype is not fully consistent with an infectious etiology. Early genomic testing, including CMA, may facilitate timely recognition of underlying genetic syndromes in children with complex neurodevelopmental presentations.<\/jats:p>","DOI":"10.3390\/diseases14060191","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:06:56Z","timestamp":1780049216000},"page":"191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Suspected Congenital Cytomegalovirus Infection to Malan Syndrome: Delayed Genetic Diagnosis Due to Diagnostic Anchoring"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-2153","authenticated-orcid":false,"given":"Gordana","family":"Kovacevic","sequence":"first","affiliation":[{"name":"Department of Neurology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6238-5936","authenticated-orcid":false,"given":"Sanja","family":"Cirkovic","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9115-7481","authenticated-orcid":false,"given":"Gordana","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-4272","authenticated-orcid":false,"given":"Maja","family":"Stanojevic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11070 Belgrade, Serbia"},{"name":"Institute of Microbiology and Immunology, Dr Subotica 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Lalic","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-208X","authenticated-orcid":false,"given":"Nikola","family":"Ilic","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8979-0445","authenticated-orcid":false,"given":"Slavica","family":"Ostojic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Siljic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11070 Belgrade, Serbia"},{"name":"Institute of Microbiology and Immunology, Dr Subotica 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Alimpic","sequence":"additional","affiliation":[{"name":"Day Hospital Care, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milanka","family":"Tesic","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplant Department, Mother and Child Health Care Institute of Serbia \u201cDr Vukan 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Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrijan","family":"Sarajlija","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11070 Belgrade, Serbia"},{"name":"Division of Clinical Genetics, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11070 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","article-title":"Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies","volume":"86","author":"Miller","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1177\/19345798251372555","article-title":"Deceptive appearances: Congenital infections simulating genetic syndromes in fetal pathology","volume":"19","author":"Mangla","year":"2026","journal-title":"J. Neonatal Perinat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(2024). International System for Human Cytogenomic Nomenclature (ISCN) 2024. Cytogenet. Genome Res., 164, 1\u2013224.","DOI":"10.1159\/000538512"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of ACMG and ClinGen","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/QCO.0000000000001023","article-title":"From diagnosis to management: Current perspectives on congenital cytomegalovirus infection","volume":"37","author":"Buchfellner","year":"2024","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_6","unstructured":"Ziebold, C., and Pillarisetty, L.S. (2026). Congenital cytomegalovirus infection. StatPearls [Internet], StatPearls Publishing. Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK541003\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2120736","DOI":"10.1001\/jamanetworkopen.2021.20736","article-title":"Congenital cytomegalovirus infection burden and epidemiologic risk factors in countries with universal screening","volume":"4","author":"Ssentongo","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/CMR.00062-12","article-title":"The \u201csilent\u201d global burden of congenital cytomegalovirus","volume":"26","author":"Manicklal","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e70025","DOI":"10.1002\/bdr2.70025","article-title":"Estimating the prevalence of congenital cytomegalovirus infection due to primary maternal infection in the United States: A probabilistic risk assessment model","volume":"118","author":"Wiley","year":"2026","journal-title":"Birth Defects Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S178","DOI":"10.1093\/cid\/cit629","article-title":"Congenital cytomegalovirus infection: Clinical outcome","volume":"57","author":"Boppana","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/rmv.544","article-title":"New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection","volume":"17","author":"Dollard","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e177","DOI":"10.1016\/S1473-3099(17)30143-3","article-title":"Congenital cytomegalovirus infection in pregnancy and the neonate: Consensus recommendations for prevention, diagnosis, and therapy","volume":"17","author":"Rawlinson","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1080\/10408363.2024.2360996","article-title":"Methods applied to neonatal dried blood spot samples for secondary research purposes: A scoping review","volume":"61","author":"Canning","year":"2024","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/rmv.517","article-title":"Diagnosis of congenital CMV infection via dried blood spots","volume":"16","author":"Barbi","year":"2006","journal-title":"Rev. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0404122","DOI":"10.1128\/spectrum.04041-22","article-title":"Improved dried blood spot PCR assay for universal congenital cytomegalovirus screening in newborns","volume":"11","author":"Kim","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pellegrinelli, L., Alberti, L., Pariani, E., Barbi, M., and Binda, S. (2020). Diagnosing congenital cytomegalovirus infection: Don\u2019t get rid of dried blood spots. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-4941-z"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1001\/jama.2010.423","article-title":"Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection","volume":"303","author":"Boppana","year":"2010","journal-title":"JAMA"},{"key":"ref_18","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2024). NFIX-related Malan syndrome. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ajhg.2010.07.001","article-title":"Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome","volume":"87","author":"Malan","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1002\/humu.23563","article-title":"Further delineation of Malan syndrome","volume":"39","author":"Priolo","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e997","DOI":"10.1002\/mgg3.997","article-title":"Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature","volume":"7","author":"Bellucco","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1113\/jphysiol.2009.186437","article-title":"Genetic and functional characterisation of the P\/Q calcium channel in episodic ataxia with epilepsy","volume":"588","author":"Rajakulendran","year":"2010","journal-title":"J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/cge.14180","article-title":"Clinical and genetic characterization of CACNA1A-related disease","volume":"102","author":"Lipman","year":"2022","journal-title":"Clin. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ajhg.2016.12.013","article-title":"A recurrent de novo variant in NACC1 causes a syndrome characterized by infantile epilepsy, cataracts, and profound developmental delay","volume":"100","author":"Schoch","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/GIM.0b013e3181e59291","article-title":"A novel microdeletion\/microduplication syndrome of 19p13.13","volume":"12","author":"Dolan","year":"2010","journal-title":"Genet. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1186\/s13023-024-03288-6","article-title":"Natural history in Malan syndrome: Survey of 28 adults and literature review","volume":"19","author":"Huynh","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/ajmg.a.35790","article-title":"Apparent germline mosaicism for a novel 19p13.13 deletion disrupting NFIX and CACNA1A","volume":"161A","author":"Nimmakayalu","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Langley, E., Farach, L.S., and Mowrey, K. (2022). Case report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1044660"}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/6\/191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:15:22Z","timestamp":1780636522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/6\/191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["diseases14060191"],"URL":"https:\/\/doi.org\/10.3390\/diseases14060191","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}