The Genetics of Neurodevelopmental Disorders

Neurodevelopmental disorders arise from disturbances to various processes of brain development, which can manifest in diverse ways. They encompass many rare genetic syndromes as well as common, heritable conditions such as intellectual disability, autism, ADHD, schizophrenia and many types of epilepsy. The Genetics of Neurodevelopmental Disorders examines recent revolutionary advances in our understanding of the genetics of these disorders, exploring both basic discoveries and the translation of new findings into the clinical setting. The book begins by examining the genetic architecture and etiology of neurodevelopmental disorders. It describes the striking recent progress in identifying pathogenic mutations, which are grouped here based on the neurodevelopmental processes impacted. Subsequent chapters consider the use of cellular and animal models to elucidate the cascading consequences of such mutations, from molecular and cellular levels to emergent effects on neural circuits, brain systems and subsequent psychological development. The text concludes by examining the important clinical implications of the recent advances in the field, from recognition of the genetic causes in individual patients to development of new treatments and interventions. A timely synthesis, The Genetics of Neurodevelopmental Disorders is a unique and essential resource for neuroscientists, geneticists, neurologists and psychiatrists and an accessible and up-to-date overview for medical and science students.

Neurodevelopmental disorders arise from disturbances to various processes of brain development, which can manifest in diverse ways. They encompass many rare genetic syndromes as well as common, heritable conditions such as intellectual disability, autism, ADHD, schizophrenia and many types of epilepsy. The Genetics of Neurodevelopmental Disorders examines recent revolutionary advances in our understanding of the genetics of these disorders, exploring both basic discoveries and the translation of new findings into the clinical setting.The book begins by examining the genetic architecture and etiology of neurodevelopmental disorders. It describes the striking recent progress in identifying pathogenic mutations, which are grouped here based on the neurodevelopmental processes impacted. Subsequent chapters consider the use of cellular and animal models to elucidate the cascading consequences of such mutations, from molecular and cellular levels to emergent effects on neural circuits, brain systems and subsequent psychological development. The text concludes by examining the important clinical implications of the recent advances in the field, from recognition of the genetic causes in individual patients to development of new treatments and interventions.A timely synthesis, The Genetics of Neurodevelopmental Disorders is a unique and essential resource for neuroscientists, geneticists, neurologists and psychiatrists and an accessible and up-to-date overview for medical and science students.

List of Contributors viiForewordKevin J. Mitchell ix1 The Genetic Architecture of Neurodevelopmental Disorders 1Kevin J. Mitchell2 Overlapping Etiology of Neurodevelopmental Disorders 29Eric Kelleher and Aiden Corvin3 The Mutational Spectrum of Neurodevelopmental Disorders 49Nancy D. Merner, Patrick A. Dion, and Guy A. Rouleau4 The Role of Genetic Interactions in Neurodevelopmental Disorders 69Jason H. Moore and Kevin J. Mitchell5 Developmental Instability, Mutation Load, and Neurodevelopmental Disorders 81Ronald A. Yeo and Steven W. Gangestad6 Environmental Factors and Gene-Environment Interactions 111John McGrath7 The Genetics of Brain Malformations 129M. Chiara Manzini and Christopher A. Walsh8 Disorders of Axon Guidance 155Heike Blockus and Alain Chédotal9 Synaptic Disorders 195Catalina Betancur and Kevin J. Mitchell10 Human Stem Cell Models of Neurodevelopmental Disorders 239Peter Kirwan and Frederick J. Livesey11 Animal Models for Neurodevelopmental Disorders 261Hala Harony-Nicolas and Joseph D. Buxbaum12 Cascading Genetic and Environmental Effects on Development: Implications for Intervention 275Esha Massand and Annette Karmiloff-Smith13 Human Genetics and Clinical Aspects of Neurodevelopmental Disorders 289Gholson J. Lyon and Jason O'Rawe14 Progress Toward Therapies and Interventions for Neurodevelopmental Disorders 319Ayokunmi Ajetunmobi and Daniela TropeaSubject Index 345Gene Index 353