{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:01:11Z","timestamp":1760058071492,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Interstitial deletions of chromosome 1q are rare, with about 30 cases reported in the literature. The phenotypical features of the affected subjects described so far include microcephaly, pre- and post-natal growth retardation, psychomotor delays, ear anomalies, brachydactyly, in addition to small hands and feet, and rarely a congenital diaphragmatic hernia (CDH). Case presentation: Here, we report on a neonate with CDH, dysmorphic features, and multiple midline anomalies including a cleft palate, in whom an array-comparative genomic hybridization (a-CGH) analysis allowed the identification of an interstitial deletion of the long arm of chromosome 1. Our patient underwent a surgical correction of CDH on the fourth day of life, while that of cleft palate has been planned to be performed at 12 months. Conclusions: The few subjects suffering such rearrangement reported to date, along with the clinical and genetic profile of the present newborn, show that 1q deletions should be considered within the context of the \u201cinterstitial 1q deletion syndrome\u201d. Comparing our case with those described in previous studies, the involved genomic regions and the phenotypic traits are partially overlapping, although the clinical picture of the present patient is among the few ones including a congenital diaphragmatic hernia within the phenotypical spectrum. A more extensive comparative analysis of a larger number of patients with similar genetic profiles may allow for a more precise clinical and genomic characterization of this rare syndrome, and for genotype\u2013phenotype correlations.<\/jats:p>","DOI":"10.3390\/genes16030319","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:22:52Z","timestamp":1741350172000},"page":"319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interstitial 1q Deletion Syndrome: A New Patient with Congenital Diaphragmatic Hernia and Multiple Midline Anomalies"],"prefix":"10.3390","volume":"16","author":[{"given":"Gregorio","family":"Serra","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-6910","authenticated-orcid":false,"given":"Rosaria","family":"Nardello","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Antona","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-8035","authenticated-orcid":false,"given":"Maria Rita","family":"Di Pace","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Giliberti","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9576-1635","authenticated-orcid":false,"given":"Mario","family":"Giuffr\u00e8","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela Mariarosa","family":"Morreale","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-1628","authenticated-orcid":false,"given":"Ettore","family":"Piro","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid Anne Mandy","family":"Schierz","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Sergio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Valenti","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-1901","authenticated-orcid":false,"given":"Marco","family":"Pensabene","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Corsello","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1213\/ANE.0000000000004324","article-title":"Update on Congenital Diaphragmatic Hernia","volume":"131","author":"Chatterjee","year":"2020","journal-title":"Anesth. Analg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1007\/s00247-020-04718-w","article-title":"Congenital diaphragmatic hernia","volume":"50","year":"2020","journal-title":"Pediatr. Radiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/ccr3.1103","article-title":"Esophageal atresia and Beckwith-Wiedemann syndrome in one of the naturally conceived discordant newborn twins: First report","volume":"6","author":"Serra","year":"2018","journal-title":"Clin. Case Rep."},{"key":"ref_4","unstructured":"Hedrick, H.L., and Adzick, N.S. (2024). Congenital diaphragmatic hernia (CDH) in the neonate: Clinical features and diagnosis. UpToDate, preprint."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/pd.6099","article-title":"Underlying genetic etiologies of congenital diaphragmatic hernia","volume":"42","author":"Scott","year":"2022","journal-title":"Prenat. Diagn."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13052-022-01336-0","article-title":"Novel mutations of the ABCA12, KRT1 and ST14 genes in three unrelated newborns showing congenital ichthyosis","volume":"48","author":"Serra","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_7","first-page":"59","article-title":"A new mutation in EDA gene in X-linked hypohidrotic ectodermal dysplasia associated with keratoconus","volume":"64","author":"Piccione","year":"2012","journal-title":"Minerva Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13052-020-00902-8","article-title":"Neonatal hyperinsulinemic hypoglycemia: Case report of kabuki syndrome due to a novel KMT2D splicing-site mutation","volume":"46","author":"Piro","year":"2020","journal-title":"Ital. J. Pediatr."},{"key":"ref_9","unstructured":"Valutazione Antropometrica Neonatale (2025, January 06). Riferimento Carte INeS. Available online: http:\/\/www.inescharts.com."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000326057","article-title":"Normative values for testicular volume measured by ultrasonography in a normal population from infancy to adolescence","volume":"76","author":"Goede","year":"2011","journal-title":"Horm. Res. Paediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1007\/s00247-016-3681-0","article-title":"Size of testes, ovaries, uterus and breast buds by ultrasound in healthy full-term neonates ages 0\u20133 days","volume":"46","author":"Kaplan","year":"2016","journal-title":"Pediatr. Radiol."},{"key":"ref_12","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 the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet Med."},{"key":"ref_13","unstructured":"(2025, January 06). UK-WHO Growth Charts\u2013Neonatal and Infant Close Monitoring (NICM). Available online: https:\/\/www.rcpch.ac.uk\/resources\/uk-who-growth-charts-neonatal-infant-close-monitoring-nicm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000336979","article-title":"De novo deletion of 1q31.1\u2013q32.1 in a patient with developmental delay and behavioral disorders","volume":"136","author":"Milani","year":"2012","journal-title":"Cytogenet. Genome Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/MCD.0000000000000281","article-title":"Chromosome 1q31.2q32.1 deletion in an adult male with intellectual disability, dysmorphic features and obesity","volume":"28","author":"Hyder","year":"2019","journal-title":"Clin. Dysmorphol."},{"key":"ref_16","first-page":"2501741","article-title":"De Novo Interstitial Microdeletion at 1q32.1 in a 10-Year-Old Boy with Developmental Delay and Dysmorphism","volume":"2016","author":"Carter","year":"2016","journal-title":"Case Rep. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1002\/ajmg.a.35334","article-title":"14q13.1-21.1 deletion encompassing the HPE8 locus in an adolescent with intellectual disability and bilateral microphthalmia, but without holoprosencephaly","volume":"158A","author":"Piccione","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13052-022-01365-9","article-title":"Congenital hypopituitarism and multiple midline defects in a newborn with non-familial Cat Eye syndrome","volume":"48","author":"Serra","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13052-022-01218-5","article-title":"Hypertrophic pyloric stenosis masked by kidney failure in a male infant with a contiguous gene deletion syndrome at Xp22.31 involving the steroid sulfatase gene: Case report","volume":"48","author":"Schierz","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_20","first-page":"105","article-title":"A case of interstitial 1q deletion [46,XY,del(q25q32.1)]","volume":"30","author":"Hamano","year":"1987","journal-title":"Ann. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1002\/ajmg.a.31776","article-title":"A 2-Mb critical region implicated in the microcephaly associated with terminal 1q deletion syndrome","volume":"143A","author":"Hill","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/ajmg.b.32427","article-title":"Reinforcing the association between distal 1q CNVs and structural brain disorder: A case of a complex 1q43\u2013q44 CNV and a review of the literature","volume":"171B","author":"Hemming","year":"2016","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1002\/ajmg.a.63344","article-title":"Associated anomalies in Pierre Robin sequence","volume":"191","author":"Stoll","year":"2023","journal-title":"Am. J. Med. Genet. A."},{"key":"ref_24","first-page":"86","article-title":"Pierre Robin Sequence: Diagnostic Difficulties Faced while Differentiating Isolated and Syndromic Forms","volume":"63","author":"Meshram","year":"2020","journal-title":"Acta Medica"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.pediatrneurol.2023.01.010","article-title":"Babies with Pierre Robin Sequence: Neuropsychomotor Development","volume":"141","author":"Padovani","year":"2023","journal-title":"Pediatr. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ejhg.2011.171","article-title":"Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43\u2013q44","volume":"20","author":"Nagamani","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000535660","article-title":"Expanding the Clinical and Molecular Spectrum of FOXG1- and ZBTB18-Associated Neurodevelopmental Disorders","volume":"163","author":"Iglesias","year":"2023","journal-title":"Cytogenet. Genome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e35908","DOI":"10.1097\/MD.0000000000035908","article-title":"A de novo variant in ZBTB18 gene caused autosomal dominant non-syndromic intellectual disability 22 syndrome: A case report and literature review","volume":"103","author":"Yang","year":"2024","journal-title":"Medicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1097\/GIM.0b013e3181484b49","article-title":"The discovery of microdeletion syndromes in the post-genomic era: Review of the methodology and characterization of a new 1q41q42 microdeletion syndrome","volume":"9","author":"Shaffer","year":"2007","journal-title":"Genet. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1002\/ajmg.a.32006","article-title":"A case of autism with an interstitial 1q deletion (1q23.3\u201324.2) and a de novo translocation of chromosomes 1q and 5q","volume":"143A","author":"Lonardo","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1597\/1545-1569_1993_030_0586_pdotla_2.3.co_2","article-title":"Proximal deletion of the long arm of chromosome 1: [del(1)(q23\u2013q25)]","volume":"30","author":"Lo","year":"1993","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_32","first-page":"8","article-title":"A new case of interstitial 1q 25.3-32.1 deletion: Cytogenetic analysis molecular characterization and ultrasound findings","volume":"9","author":"Libotte","year":"2015","journal-title":"J. Prenat. Med."},{"key":"ref_33","first-page":"e918128","article-title":"Chromosome 1q Terminal Deletion and Congenital Glaucoma: A Case Report","volume":"21","author":"Dirar","year":"2020","journal-title":"Am. J. Case Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/ana.26662","article-title":"KCNT2-Related Disorders: Phenotypes, Functional, and Pharmacological Properties","volume":"94","author":"Cioclu","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1002\/ajmg.a.62370","article-title":"Recurrent KCNT2 missense variants affecting p.Arg190 result in a recognizable phenotype","volume":"185","author":"Jackson","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/cga.12356","article-title":"Tumor predisposition in an individual with chromosomal rearrangements of 1q31.2-q41 encompassing cell division cycle protein 73","volume":"60","author":"Nishimura","year":"2020","journal-title":"Congenit. Anom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s10038-023-01129-1","article-title":"CFH-CFHR1 hybrid genes in two cases of atypical hemolytic uremic syndrome","volume":"68","author":"Sugawara","year":"2023","journal-title":"J. Hum. Genet."},{"key":"ref_38","first-page":"9987","article-title":"Clinical research advances of CFHR5 nephropathy: A recent review","volume":"27","author":"Fei","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"160","DOI":"10.5482\/HAMO-13-08-0046","article-title":"Coagulation factor XIII deficiency. Diagnosis, prevalence and management of inherited and acquired forms","volume":"34","author":"Biswas","year":"2014","journal-title":"Hamostaseologie"},{"key":"ref_40","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (2020). ASPM Primary Microcephaly. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Daher, A., Banjak, M., Noureldine, J., Nehme, J., and El Shamieh, S. (2024). Genotype-phenotype associations in CRB1 bi-allelic patients: A novel mutation, a systematic review and meta-analysis. BMC Ophthalmol., 24.","DOI":"10.1186\/s12886-024-03419-4"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/hmg\/ddab248","article-title":"Pathogenic variants in nucleoporin TPR (translocated promoter region, nuclear basket protein) cause severe intellectual disability in humans","volume":"31","author":"Bell","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Berkowcz, S.R., Featherby, T.J., Whisstock, J.C., and Bird, P.I. (2016). Mice Lacking Brinp2 or Brinp3, or both, exhibit behaviors consistent with neurodevelopmental disorders. Front. Behav. Neurosci., 10.","DOI":"10.3389\/fnbeh.2016.00196"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/3\/319\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:49:13Z","timestamp":1760028553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/3\/319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,7]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["genes16030319"],"URL":"https:\/\/doi.org\/10.3390\/genes16030319","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2025,3,7]]}}}