This is an outstanding book for both clinicians and researchers. The volume is divided into three sections. The first describes a variety of neurodevelopmental disorders, including Down syndrome, Smith-Magenis syndrome, fragile X syndrome and premutation disorders, Prader-Willi syndrome, Williams syndrome, and fetal alcohol spectrum disorder. The second section addresses several aspects of treatment, including psychopharmacology, behavioral interventions, and speech and language therapy. The third section includes future directions in diagnosis and treatment. Each section consists of a detailed review of the current literature, which is almost impossible to keep up with, even for those in the field. The authors of nearly all of the chapters are leaders in the field, and thus their insight and pearls of wisdom are a pleasure from which to learn.
Highlights of the first section include the initial chapter describing behavioral phenotypes, with a detailed historical perspective that only James Harris can do, in his erudite and informative style. Each chapter covers a neurodevelopmental disorder and includes the latest data on genetic information and genotype-phenotype correlations. In the chapter on Smith-Magenis syndrome, Andrea Gropman and Ann Smith not only cover flanking genes well, and these genes' additive features to the phenotype, but they also discuss general mechanisms of deletion that occur across disorders. Walter Kaufmann does an outstanding job in covering the expanded phenotypes of not only fragile X syndrome caused by the full mutation at FMR1 but also by premutation disorders, which includes their association with autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and adult neurodegeneration leading to the fragile X-associated tremor ataxia syndrome. Kaufmann's discussion of the association of fragile X syndrome and autism is thorough and reflects his excellent research covering the relationship of social anxiety, social withdrawal, and autism spectrum disorder. George Capone excels in his discussion of frontal-caudate/putamen-thalamic circuits and their relationship to stereotypic behavior in Down syndrome. His discussion is pertinent to many other neurodevelopmental disorders that involve executive function deficits and ADHD. His description of neurobiological events “that are played out in utero and continue to reverberate with lifelong repercussions for cognitive, behavioral and emotional function” is true for most of the neurogenetic disorders. Travis Thompson reviews endophenotype similarities between Prader-Willi syndrome and autism and helps us understand the commonalities across disorders as they relate to autistic features of stereotypes, social avoidance, and social deficits. Carolyn Mervis and Angela John cover Williams syndrome, and their historical perspective of the controversy regarding the modularity of language as differentiated from intellectual abilities is exceptional. They relate detailed neuropsychological studies to new magnetic resonance imaging studies. These studies have found that the reduced sulcal depth of gray matter in the extraparietal sulcus serves as a roadblock to dorsal stream processing in this syndrome. This may explain the visual spatial constructional deficits and perhaps the relational language deficits seen in Williams syndrome. There may be a central processing center for spatial, temporal, and quantitative processing that is affected not only in Williams syndrome but also in other neurodevelopmental disorders.
It is good to see fetal alcohol spectrum disorder covered in this volume on neurogenetic disorders because it is very common with a phenotype that has several similarities to many neurogenetic disorders, and yet it is from an environmental toxin. It reminds us that the phenotypic spectrum that we see in a given disorder may be influenced by environmental toxins that can have combined effects with the genetic component. I reflect on the many patients I have seen with fetal alcohol spectrum disorder and fragile X syndrome together and hypothesize about the consistency of the combined phenotype and drug responsiveness. There is much to do in research to understand both the influences of background genetic effects and the environmental influences on the children we see.
The discussions in the second section, on the treatment of patients with neurogenetic syndromes, lack the specificity of the first section and do not similarly address the advances that have occurred in understanding the neurobiology of these disorders. There are general chapters on functional behavior assessment and applied behavior analysis in addition to- -psychopharmacologic interventions for developmental disorders generally as well as language intervention. The speech-language chapter focuses on a case of severe prematurity and neonatal complications, but there is a lack of information about specific interventions for neurogenetic disorders. This is a remarkable missed opportunity considering that the title of this book is Neurogenetic Syndromes. One highlight of this section is the chapter by Ferrell concerning psychiatric diagnoses in neurodevelopmental disorders because he gives a detailed historical perspective on treatment, beginning with Esquirol in France to the pioneering reforms of Dorothea Dix in the United States as well as the work of Robert Sovner.
In the third section on future implications and directions, Emrick begins by reviewing basic principles in genetics that would be helpful for nonprofessionals, but her discussion of comparative genomic hybridization, linkage studies, and epigenetic and environmental influences on the genome are well worth reading for those in this field. Finestein and Verma pre-sent a worthwhile discussion of how advances in understanding the neuroscience of behavioral phenotypes of neurogenetic disorders have outstripped the usefulness of DSM-IV psychiatric diagnoses for these disorders. They -demonstrate their point with a thorough discussion of the social phenotypes in each disorder outlined in the first section. Although -Accardo and Jaworski give a detailed perspective of the advances that occurred during the 19th-21st centuries, they do not describe the advances in targeted therapeutics for neurogenetic syndromes. This is the most exciting current and future prospect in the field of neurogenetic disorders and is gaining momentum, but sadly it is not discussed in this “future” section.
Overall this book has a number of strengths, and I recommend it highly for practitioners and researchers. A theme of commonalities across disorders is seen throughout the volume. Whether it is frontal-striatal deficits associated with ADHD or social emotional deficits related to autism spectrum disorder, these themes are informative for whatever expertise you have. This book demonstrates that we have much to learn from the study of neurogenetic disorders that can inform treatment for all populations and even those with psychiatric problems or learning disabilities in the general population with as yet unknown neurogenetic components.