The Conundrum of Mechanics Versus Genetics in Congenital Hydrocephalus and Its Implications for Fetal Therapy Approaches: A Scoping Review.

Autor:	Herzeg A; Department of Surgery, University of California, San Francisco, San Francisco, California, USA.; UCSF Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, California, USA.; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.; Department of Obstetrics and Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA., Borges B; Department of Surgery, University of California, San Francisco, San Francisco, California, USA.; UCSF Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, California, USA.; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA., Diafos LN; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.; Department of Pediatrics and Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA., Gupta N; UCSF Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, California, USA.; Department of Pediatrics and Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA.; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.; Brain Tumor Research Center, University of California, San Francisco, San Francisco, California, USA., MacKenzie TC; Department of Surgery, University of California, San Francisco, San Francisco, California, USA.; UCSF Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, California, USA.; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.; Department of Obstetrics and Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.; Department of Pediatrics and Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA., Sanders SJ; UCSF Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, California, USA.; Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Institute for Developmental and Regenerative Medicine, Oxford University, Oxford, UK.
Jazyk:	angličtina
Zdroj:	Prenatal diagnosis [Prenat Diagn] 2024 Oct; Vol. 44 (11), pp. 1354-1366. Date of Electronic Publication: 2024 Sep 01.
DOI:	10.1002/pd.6654
Abstrakt:	Recent advances in gene therapy, particularly for single-gene disorders (SGDs), have led to significant progress in developing innovative precision medicine approaches that hold promise for treating conditions such as primary hydrocephalus (CH), which is characterized by increased cerebrospinal fluid (CSF) volumes and cerebral ventricular dilation as a result of impaired brain development, often due to genetic causes. CH is a significant contributor to childhood morbidity and mortality and a driver of healthcare costs. In many cases, prenatal ultrasound can readily identify ventriculomegaly as early as 14-20 weeks of gestation, with severe cases showing poor neurodevelopmental outcomes. Postnatal surgical approaches, such as ventriculoperitoneal shunts, do not address the underlying genetic causes, have high complication rates, and result in a marginal improvement of neurocognitive deficits. Prenatal somatic cell gene therapy (PSCGT) promises a novel approach to conditions such as CH by targeting genetic mutations in utero, potentially improving long-term outcomes. To better understand the pathophysiology, genetic basis, and molecular pathomechanisms of CH, we conducted a scoping review of the literature that identified over 160 published genes linked to CH. Mutations in L1CAM, TRIM71, MPDZ, and CCDC88C play a critical role in neural stem cell development, subventricular zone architecture, and the maintenance of the neural stem cell niche, driving the development of CH. Early prenatal interventions targeting these genes could curb the development of the expected CH phenotype, improve neurodevelopmental outcomes, and possibly limit the need for surgical approaches. However, further research is needed to establish robust genotype-phenotype correlations and develop safe and effective PSCGT strategies for CH. (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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