Fetal malformations of cortical development: review and clinical guidance

Jeffrey B Russ; Sonika Agarwal; Charu Venkatesan; Barbara Scelsa; Brigitte Vollmer; Tomo Tarui; Andrea C Pardo; Monica E Lemmon; Sarah B Mulkey; Anthony R Hart; Usha D Nagaraj; Jeffrey A Kuller; Matthew T Whitehead; Jennifer L Cohen; Juliana S Gebb; Orit A Glenn; Mary E Norton; Dawn Gano

doi:10.1093/brain/awaf094

Fetal malformations of cortical development: review and clinical guidance

Brain. 2025 Jun 3;148(6):1888-1903. doi: 10.1093/brain/awaf094.

Authors

Jeffrey B Russ¹, Sonika Agarwal², Charu Venkatesan³, Barbara Scelsa⁴, Brigitte Vollmer^{5

6}, Tomo Tarui⁷, Andrea C Pardo⁸, Monica E Lemmon^{1

9}, Sarah B Mulkey^{10

11}, Anthony R Hart¹², Usha D Nagaraj¹³, Jeffrey A Kuller¹⁴, Matthew T Whitehead^{15

16}, Jennifer L Cohen¹⁷, Juliana S Gebb¹⁸, Orit A Glenn¹⁹, Mary E Norton²⁰, Dawn Gano²¹

Affiliations

¹ Division of Neurology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
² Division of Neurology and Pediatrics, Children's Hospital of Philadelphia; Division of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
³ Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
⁴ Department of Pediatric Neurology, Buzzi Children's Hospital, University of Milan, Milan 20154, Italy.
⁵ Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
⁶ Paediatric and Neonatal Neurology, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
⁷ Division of Pediatric Neurology, Hasbro Children's Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
⁸ Department of Pediatrics, Division of Neurology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
⁹ Department of Population Health Sciences, Duke University School of Medicine, Durham, NC 27710, USA.
¹⁰ Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington DC 20010, USA.
¹¹ Departments of Neurology and Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington DC 20010, USA.
¹² Department of Paediatric Neurology, King's College Hospital NHS Foundation Trust, London SE5 9RS, UK.
¹³ Division of Radiology and Medical Imaging, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
¹⁴ Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.
¹⁵ Division of Neuroradiology, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
¹⁶ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁷ Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
¹⁸ Richard D. Wood Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
¹⁹ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94158, USA.
²⁰ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
²¹ Department of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA 94158, USA.

Abstract

Malformations of cortical development (MCDs) are a heterogeneous family of congenital brain malformations that originate from disturbed development of the cerebral cortex. MCDs can arise from primary genetic disorders that lead to dysfunction of the molecular processes controlling neuronal proliferation, neuronal migration, cortical folding or cortical organization. MCDs can also result from secondary, disruptive causes, such as congenital infection or other in utero brain injuries. Sequelae of MCDs can include epilepsy, intellectual disability and cerebral palsy, among other symptoms, with a high burden of paediatric morbidity. Advances in antenatal genetic testing and imaging have improved the ability to diagnose MCDs, yet limited literature exists to aid clinicians in prognostication of outcomes and perinatal management. These clinical realities can make it challenging for clinicians caring for fetal neurological conditions to counsel families and make recommendations for interdisciplinary care. We aim to review the literature on fetal MCDs and present practice guidelines for clinicians regarding the pre- and postnatal management of MCDs.

Keywords: fetal neurology; heterotopia; lissencephaly; polymicrogyria; prenatal diagnosis; schizencephaly.

Publication types

Review

MeSH terms

Cerebral Cortex* / abnormalities
Female
Humans
Malformations of Cortical Development* / complications
Malformations of Cortical Development* / diagnosis
Malformations of Cortical Development* / therapy
Pregnancy
Prenatal Diagnosis / methods

Abstract

Publication types

MeSH terms

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