Prenatal Diagnosis of <i>MSL2</i>-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication

Article Article scientifique Rapport de cas Prenatal Diagnosis of <i>MSL2</i>-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication eng 2025-09-15 2026-03 author Zgheib Omar 0000-0002-7520-4046 Division of Medical Genetics, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 642767 author Rio Frio Thomas Molecular Diagnostics Laboratory, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 409061 author Pellegrinelli Gianmaria Division of Fetal Medicine, Department of Obstetrics, Gynecology and Pediatrics, Geneva University Hospitals, Geneva, Switzerland. 30033 author Gimelli Stefania Cytogenetics Laboratory, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 663673 author Marconi Caterina Cytogenetics Laboratory, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 457082 author Le Mercier Delphine Division of Fetal Medicine, Department of Obstetrics, Gynecology and Pediatrics, Geneva University Hospitals, Geneva, Switzerland. 410534 author Rebollo Polo Monica 0000-0001-9756-9671 Division of Radiology, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 410125 author Habre Céline Division of Radiology, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 643255 author Fluss Joel Victor Division of Neuropediatrics, Department of Obstetrics, Gynecology and Pediatrics, Geneva University Hospitals, Geneva, Switzerland. 28801 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Ha-Vinh Leuchter Russia Division of Child Development, Department of Obstetrics, Gynecology and Pediatrics, Geneva University Hospitals, Geneva, Switzerland. 710706 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) Elisa Russia Tuyet Mai Ha Vinh Leuchter author Abramowicz Marc Division of Medical Genetics, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 884432 Département de médecine génétique et développement (GEDEV) author Giannini Rosalinda Division of Medical Genetics, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 430911 author Fokstuen Siv Division of Medical Genetics, Diagnostics Department, Geneva University Hospitals, Geneva, Switzerland. 133715 Département de médecine génétique et développement (GEDEV) 581-585 10.1111/cge.70071 40954079 0009-9163 PMC12881215 The Male-Specific Lethal 2 Homolog (MSL2) gene was recently reported to be responsible for a novel, rather severe neurodevelopmental syndrome including brain abnormalities. We report the first prenatal case of an MSL2-related pathology caused by a de novo MSL2 splice variant (c.142+1G>T). RNA study on amniotic fluid cells showed an intronic inclusion and frameshift, consistent with loss-of-function intolerance. The fetus, who presented with bilateral moderate ventriculomegaly, also carried a paternally inherited 15q13 microduplication. Brain MRI at 2 and 4 months of age showed stable, mildly enlarged lateral ventricles. Clinical evaluation at 11 months revealed only a mild developmental delay. This case illustrates the challenges in predicting the postnatal outcome of recently characterized syndromes with limited documented cases, especially in association with a second independent genetic anomaly. Follow-up will be crucial to better define the developmental impact of this first reported MSL2 splice mutation in combination with the 15q13 microduplication, and characterization of more patients with MSL2 mutations will contribute to expanding the phenotypic spectrum. Humans Female Chromosomes, Human, Pair 15 / genetics Prenatal Diagnosis Pregnancy Male Hydrocephalus / genetics Hydrocephalus / diagnosis Chromosome Duplication / genetics Intellectual Disability / genetics Intellectual Disability / diagnosis Infant Magnetic Resonance Imaging Adult Chromosome Aberrations Dewey 616.0757 Dewey 616 Dewey 618 Dewey 576.5 58 Département de pédiatrie, gynécologie et obstétrique 223 135 Département de médecine génétique et développement 21D 56 Département de médecine 221 62 Département de radiologie et informatique médicale 227 false 150 L'imagerie cérébrale 184 1297 Abramowicz Lab 1013 Clinical genetics 109 3 71bb44a0-127e-47bf-92c9-4384a3aa684e Article (Published version) Public Article_scientifique_from_europePmc.pdf 739510 application/pdf CC BY-4.0 b6a35d7bf0815311e180ffedb2ce102e0718d795bbb1cb58b57daee93523561d openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale

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Prenatal Diagnosis of MSL2-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication	Clinical genetics			2026	1	0

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