What Is Weaver Syndrome?

Introduction

Weaver syndrome, also known as Weaver-Smith syndrome, is a perplexing and exceedingly rare genetic disorder characterised by an abnormal and excessive growth of bone tissue.¹ This condition poses clinical and developmental challenges and can have potential health complications if symptoms are left untreated and appropriate accommodations are not made. 

Although its rarity has rendered it a subject of limited research and awareness, Weaver syndrome significantly impacts the lives of affected individuals and their families. Keep reading for an in-depth exploration of Weaver syndrome, its genetic basis, clinical presentation, diagnosis, management, and the broader implications of living with this unique condition.

Genetic Basis of Weaver Syndrome

Understanding the genetic basis of Weaver syndrome is fundamental to unravelling its complex pathophysiology. At the heart of this condition lies genetic mutations, in particular changes in the EZH2 gene. These mutations trigger a cascade of intricate processes within the body, ultimately culminating in the hallmark features and challenges associated with Weaver syndrome.² The process is thought to be caused due to the mutations causing malfunctioning in the repression of growth, especially in bone tissue.

It is important to note that not all cases of Weaver syndrome result from inheritance.³ Approximately half of affected individuals inherit the EZH2 gene mutation from a parent who carries it, resulting in a 50% chance of transmission during each pregnancy. However, Weaver syndrome can also manifest spontaneously, devoid of any familial precedent.⁴ This genetic complexity underscores the individuality of each person's experience with Weaver syndrome, as both inherited and sporadic cases contribute to its overall rarity.

Clinical Manifestations and symptoms of Weaver Syndrome

Weaver syndrome has a notable degree of clinical variability, presenting a considerable challenge in trying to understand the disease as a set of symptoms that follow a uniform description.⁵ Nevertheless, some common features are frequently observed in individuals with this condition, offering insight into the clinical landscape of Weaver syndrome.

• Excessive Growth: a defining characteristic of Weaver syndrome is rapid and excessive growth, especially in the affected individual’s bones, resulting in tall stature. This accelerated growth often becomes evident during prenatal ultrasounds when foetal bones appear elongated, leading to a diagnosis of macrosomia (higher-than-average birth weight) upon delivery.¹
• Distinctive Facial Features: Weaver syndrome can give rise to distinctive alterations in facial and cranial features. These include a broad forehead, epicanthal folds (extra skin near the inner corners of the eyes), down-slanting eyelids, widely spaced eyes, macrocephaly (an enlarged head), large or low-set ears, an elongated groove between the upper lip and nose, and micrognathia (a small lower jaw).
• Musculoskeletal Abnormalities: the condition exerts its effects on the musculoskeletal system, leading to a range of challenges. These can encompass joint deformities, clubfoot, difficulties in straightening elbows or knees, camptodactyly (fingers that cannot straighten) with wide thumbs, and variations in muscle tone within the abdomen, which may result in hernias.⁶ In other cases, patients have had problems with their hip and ankle joints.⁷
• Developmental Delays: Weaver syndrome can significantly impact developmental milestones in infants and toddlers, leading to delays in achieving typical developmental markers, due to problems with motor and neural development. As a result, individuals may require tailored support and interventions to address these developmental challenges.
• Intellectual Disabilities: intellectual disabilities are a prominent aspect of Weaver syndrome, manifesting in varying degrees of severity, from mild to moderate. These intellectual challenges can significantly affect an individual's learning abilities and daily functioning but may be overcome with the right support.
• Health Complications: some individuals with Weaver syndrome may face heightened risks of specific health complications. These can include congenital heart defects and an increased susceptibility to neuroblastoma, a childhood cancer primarily affecting children under the age of five.^8,9

Comorbidity with neuroblastoma

In some instances, Weaver Syndrome may go undetected until signs of neuroblastoma are observed. Neuroblastoma is a form of cancer that forms  in nerve cells when an embryo or foetus is developing. Collective signs that a child may have neuroblastoma are:

• Bumps or lumps on the torso or neck
• Lumps under the skin that are not tender to the touch
• Protruding eyeballs and dark circles under eyes
• Wheezing and chest pain
• Abdominal pain
• Changes in bowel habits i.e. constipation or diarrhoea

Diagnosis of Weaver Syndrome

The diagnosis of Weaver syndrome typically commences with a comprehensive clinical evaluation conducted by healthcare providers specialising in genetics and rare genetic disorders. The suspicion of Weaver syndrome often arises from the distinct physical features and developmental challenges observed in affected individuals.

To definitively confirm the diagnosis, genetic tests are usually performed to identify the presence of the EZH2 gene mutation1. These genetic tests include collecting a small blood sample, which is then sent to a specialised genetic laboratory for a series of tests. These tests are essential in confirming the presence of the specific genetic mutation associated with Weaver syndrome.¹⁰

In certain scenarios, healthcare providers may opt for broader genetic testing panels to exclude other genetic disorders that share clinical similarities with Weaver syndrome. This approach is particularly relevant when conditions such as Sotos syndrome exhibit overlapping symptoms.⁵ Genetic testing panels empower healthcare providers to pinpoint the specific gene mutations related to Weaver syndrome or similar genetic conditions, ensuring precise diagnosis and tailored care plans.

Management and Treatment of Weaver Syndrome

There is currently no cure for Weaver syndrome, and treatment is focused on managing symptoms. It is best for healthcare providers to collaborate closely with affected individuals and their families to formulate comprehensive care plans tailored to address the unique needs and challenges posed by the condition. These care plans are designed to enhance the overall quality of life for individuals with Weaver syndrome.

The components of a typical care plan are highly individualised and meticulously tailored to each person's specific requirements, strengths, and challenges associated with Weaver syndrome. The following elements are often integrated into these personalised care plans:

• Behavioural Health Support: given the considerable variability in intellectual abilities among individuals with Weaver syndrome, specialised behavioural health services are often a critical component of care plans. These services aim to address intellectual disabilities, facilitate effective communication, and foster improved social interactions.
• Cardiovascular Care: for individuals with congenital heart defects, specialised cardiovascular care is essential. This care encompasses diagnosis, management, and potential surgical intervention when necessary.
• Educational Support: additional educational support, such as tutoring or counselling, is frequently vital to help individuals with Weaver syndrome thrive academically and navigate the learning process effectively.
• Orthopaedic Interventions: depending on the extent of musculoskeletal abnormalities, orthopaedic surgery or procedures may be recommended. These interventions aim to improve joint function and mobility.
• Physical Therapy: physical therapy programs are instrumental in developing muscle strength, coordination, and motor skills. These programs contribute to enhanced mobility and increased independence.

Living With Weaver Syndrome

Living with Weaver syndrome extends beyond medical management, encompassing a wide array of emotional, educational, and social considerations. Regular consultations with healthcare providers are essential to monitor symptoms and ensure individuals receive the necessary care.¹⁰

Families and caregivers play a pivotal role in supporting individuals with Weaver syndrome. They offer emotional support, advocate for the unique needs of affected individuals, and create nurturing and inclusive environments. Community education and awareness efforts are essential in promoting understanding and acceptance of individuals with rare genetic conditions like Weaver syndrome.

Summary

Weaver syndrome represents an extraordinarily rare genetic disorder characterised by excessive bone growth and a range of physical and developmental challenges. While a cure remains elusive, individuals with Weaver syndrome can lead fulfilling lives with the provision of appropriate medical care, educational support, and a nurturing environment.

Genetic testing and individualised care plans play pivotal roles in enhancing the quality of life for those affected by this condition. By fostering understanding and empathy within society, we can contribute to a more inclusive and supportive environment for individuals and families grappling with the complexities of rare genetic conditions like Weaver syndrome.

Moreover, advocacy and research initiatives hold the potential to further our understanding of Weaver syndrome, paving the way for improved diagnostic methods, therapeutic interventions, and a brighter future for those living with this rare genetic disorder. In embracing the unique journeys of individuals with Weaver syndrome, we advance toward a more compassionate and inclusive world.