Fragile X Syndrome and Premutation Disorders

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 Neuropediatrics 2021
https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0041-1728657

Eugen Boltshauser, Neuropediatrics, 2021

'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

David J Amor, Developmental Medicine & Child Neurology, 2020