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.

List of Contributors vii

Foreword
Kevin J. Mitchell ix

1 The Genetic Architecture of Neurodevelopmental Disorders 1
Kevin J. Mitchell

2 Overlapping Etiology of Neurodevelopmental Disorders 29
Eric Kelleher and Aiden Corvin

3 The Mutational Spectrum of Neurodevelopmental Disorders 49
Nancy D. Merner, Patrick A. Dion, and Guy A. Rouleau

4 The Role of Genetic Interactions in Neurodevelopmental Disorders 69
Jason H. Moore and Kevin J. Mitchell

5 Developmental Instability, Mutation Load, and Neurodevelopmental Disorders 81
Ronald A. Yeo and Steven W. Gangestad

6 Environmental Factors and Gene–Environment Interactions 111
John McGrath

7 The Genetics of Brain Malformations 129
M. Chiara Manzini and Christopher A. Walsh

8 Disorders of Axon Guidance 155
Heike Blockus and Alain Chédotal

9 Synaptic Disorders 195
Catalina Betancur and Kevin J. Mitchell

10 Human Stem Cell Models of Neurodevelopmental Disorders 239
Peter Kirwan and Frederick J. Livesey

11 Animal Models for Neurodevelopmental Disorders 261
Hala Harony-Nicolas and Joseph D. Buxbaum

12 Cascading Genetic and Environmental Effects on Development: Implications for Intervention 275
Esha Massand and Annette Karmiloff-Smith

13 Human Genetics and Clinical Aspects of Neurodevelopmental Disorders 289
Gholson J. Lyon and Jason O'Rawe

14 Progress Toward Therapies and Interventions for Neurodevelopmental Disorders 319
Ayokunmi Ajetunmobi and Daniela Tropea

Subject Index 345

Gene Index 353