Fragile X Syndrome and Premutation Disorders Hagerman

Fragile X Syndrome and Premutation Disorders

New Developments and Treatments

Product Type: Print Edition (Complete Book)

ISBN: 9781911612377

Randi J Hagerman (Editor), Paul J Hagerman (Editor)

Series: Clinics in Developmental Medicine

Edition: 1st

Publication date: November 2020

Page count: 192

Buy now from Mac Keith Press


You can download chapters or sections from this book

Fragile X syndrome results from a gene mutation on the X-chromosome, which leads to various intellectual and developmental disabilities. Fragile X Syndrome and Premutation Disorders offers clinicians and families a multidisciplinary approach in order to provide the best possible care for patients with Fragile X. Unique features of the book include what to do when an infant or toddler is first diagnosed, the impact on the family and an international perspective on how different cultures perceive the syndrome.

  • Presents up-to-date diagnostic and treatment approaches for Fragile X syndrome and other premutation disorders, including FXTAS, FXPOI and FXAND
  • Summary of new beneficial treatments from a molecular/neurobiological standpoint
  • Practical clinical strategies for managing both behavioural and medical aspects of the syndrome
  • Explores the unique effects of the disorder on women


This book will be of interest  to Paediatricians, Paediatric Neurologists, Allied Health Professionals and families.

From the Foreword

“This book is an essential addition to the existing literature, offering a wealth of information on all clinical and molecular aspects of the Fragile X syndrome mutation in one place.”

Professor Frank Kooy, University of Antwerp, Edegem, Belgium

Clinics in Developmental Medicine

Randi J Hagerman (Editor)

Randi J. Hagerman

Randi J Hagerman, M.D., FAAP, is a Distinguished Professor of Pediatrics at the University of California Davis Medical Center and Director of the Fragile X Research and Treatment Center at the MIND Institute and holds an Endowed Chair in Fragile X Research. Dr Hagerman is a developmental and behavioral pediatrician and has studied patients with fragile X syndrome (FXS), autism (ASD), and other neurodevelopmental disorders. She has carried out numerous targeted treatment studies in FXS and autism. She and her husband and team have published extensively regarding fragile X premutation disorders including the first description of FXTAS in 2001. She co-founded the National Fragile X Foundation in 1984 and has been involved in targeted treatments for fragile X syndrome, autism, and FXTAS for several years. Dr Hagerman has written over 400 peer-reviewed articles and several books on fragile X and autism.

Paul J Hagerman (Editor)

Paul J. Hagerman

Paul J Hagerman is a molecular geneticist whose interest in neurodevelopmental and neurodegenerative diseases is focused on fragile X-associated disorders. In 2001, Drs. Hagerman discovered the neurological disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), which affects “premutation” carriers of the fragile X (FMR1) gene, one of the most common single-gene neurodegenerative disorders. The Hagerman lab also discovered the mRNA dysregulation that underlies the pathogenesis of FXTAS; the lab has since helped to identify the core molecular processes underpinning FXTAS. The Hagerman lab has published the first systematic investigation of the relationship between the fragile X protein (FMRP) and IQ.

  • Contents
  • 1. Overview of FXS and Fragile X Spectrum Disorders
  • Randi J Hagerman
  • 2. Autism Spectrum Disorders and Fragile X Syndrome: Intertwined and Guiding Interventions
  • Leonard Abbeduto, Angela John Thurman and Jenniffer Villarreal
  • 3. The Diagnosis of Fragile X syndrome: New Advances, Population Screening and Cascade Testing
  • Mittal J Jasoliya and Flora Tassone
  • 4. Molecular Advances in Fragile X Syndrome and Fragile X-associated Disorders
  • Jamie L Randol, Malgorzata Bzymek and Paul J Hagerman
  • 5. Medical, Psychopharmacological and Targeted Treatment for FXS
  • Randi J Hagerman, Dragana Protic and Elizabeth M Berry-Kravis
  • 6. Behavioral Interventions to Improve Tantrums, Aggressions, Anxiety, and Mood Instability
  • Karen Riley, Andrea Schneider, David Hessl and Marcia L Braden
  • 7. Women’s Issues in Fragile X Spectrum Disorders
  • Jessica Ezzell Hunter, Anne C Wheeler, Emily Graves Allen, Kaitlyn Wald, Aleksandar Rajkovic, Randi J Hagerman and Stephanie L Sherman
  • 8. FXTAS: New Advances and Treatments
  • Verónica Martínez-Cerdeño, Jun Yi Wang, Jim Grigsby, Deborah Hall and Randi J Hagerman
  • 9. My baby has just been diagnosed with Fragile X Syndrome: What is there to know?
  • Susan M Rivera, Jane E Roberts, Anne C Wheeler and Randi J Hagerman
  • 10. Academic Intervention and Therapies for Children with FXS
  • Kerrie Lemons Chitwood, Laura Greiss Hess, María Diez-Juan and Marcia Braden
  • 11. International Perspective on Identification and Treatment of Fragile X Syndrome and Associated Disorders
  • Suma Shankar, Tri Indah Winarni, Weerasak Chonchaiya, Gry Hoem, Angel Belle C Dy, Lourdes Sumpaico-Tanchanco, Aruna Gowdra, Maria Jimena Salcedo-Arellano and Wilmar Saldarriaga
  • 12. Parent Advocacy and Establishing an International Parent Support Organization
  • Robert M Miller, Jayne Dixon Weber and Elizabeth M Berry-Kravis

Supplemental Material: Behavior Intervention Plan Worksheet

Provided as an Appendix to the book and as a PDF download.

'Randi and Paul Hagerman provide a timely and comprehensive update. The book covers both clinical and molecular aspects, and extends both across the spectrum of fragile X-associated disorders and also the life course, from preconception and newborn infant screening to late-onset disorders. It is aimed primarily at clinicians and researchers, with some chapters being relatively technical in presentation. But there are also parts that will be useful for educators and families who are seeking an in-depth understanding of fragile X and premutation disorders. It is at its best when dealing with the practical management and treatment aspects of fragile X disorders, as this information is not readily accessible from the published literature.' David J Amor, Developmental Medicine & Child Neurology, 2020

It is notable that both editors share the same family name, not merely a coincidence. Randi Hageman and Paul Hageman are a couple who has been at the forefront of fragile X syndrome research since 40+ years. Randi Hageman is a passionate clinician, Paul Hageman a renowned laboratory scientist. The editors and 39 contributors have compiled this volume. Note that, fragile X syndrome is the most prevalent cause of inherited intellectual disability. The book is primarily addressed to health care providers (in the broad sense) and families. I found some remarks from the editors preface worth to quote “Most of what we know we have learned from the families, but clinicians have to listen attentively ….” and “… many physicians and health care providers are focused on computers instead of their patients.” Further, Randi Hageman appropriately mentions that “information needs to go to the families so that they can educate their healthcare providers and therapists who may not be knowledgeable about the current literature.” This book provides a wealth of information for caregivers and parents, I have definitely learned a lot by “navigating” through this volume. A few aspects are mentioned. It is remarkable that a single type of mutation (CAG repeats) may lead to a spectrum of disorders such as fragile X syndrome (FXS) and full mutations >200 CAG repeats; several premutation disorders (55–200 repeats) are as follows (1) fragile X-associated tremor–ataxia syndrome (FXTAS), (2) fragile X-associated primary ovarian insufficiency (FXPOI), and (3) fragile X-associated neuropsychiatric disorders (FXAND). Hence, multiple clinical manifestations are possible presenting in distinct groups of individuals. Relevant information is provided for these various manifestations. Remarkably, “only” approximately 40% of male premutation carriers develop FXTAS, usually in their sixties, and approximately 20% of woman develop ovarian insufficiency. It is not known why less than half of premutation carriers develop symptoms. FXAND represents an umbrella term of many neuropsychiatric disorders, these problems can be experienced by approximately half of carriers. It is reminded that triplet repeat disorders usually escape the detection by exome sequencing! Besides chapters on autism spectrum disorders and FSX, diagnosis of FRX, molecular advances, and women’s issues, other chapters are dealing with “Medical, Psychopharmacological, and Targeted Treatment for FXS,” “Behavioral Intervention to Improve Tantrums, Aggression, Anxiety, and Mood Instability,” and “Academic Interventions and Therapies for Children with FXS,” and the importance of parent advocacy and parent support organization. Targeted treatment are awaited. Animal studies in the knock out mouse have demonstrated benefits of new compounds, controlled trials are currently ongoing to document safety and efficacy. Benefits from new treatments are likely better if started at an early age, timely diagnosis is crucial. This book will prove to be a useful resource, it can be highly recommended to professionals working in this field and to those wishing to better understand this complex disorder(s). Eugen Boltshauser, Department of Pediatric Neurology, University Children’s Hospital, Zurich, Switzerland. Eugen Boltshauser, Neuropediatrics, 2021.