Weaver syndrome is a rare, congenital overgrowth syndrome. This means it is a condition that is present from birth and is characterized by accelerated physical growth that often begins even before birth. In addition to being taller and heavier than their peers, children with Weaver syndrome typically have a distinctive set of physical characteristics, most notably advanced bone age and recognizable facial features.

At its core, Weaver syndrome is a disorder of epigenetic regulation. Epigenetics is a complex system that controls how our genes function.

• A helpful analogy is to think of your DNA as a vast library containing thousands of cookbooks (your genes). These books contain all the recipes for building and running the body.
• Epigenetics is the library’s sophisticated control system. It is like a team of librarians who use a system of “sticky notes” and “highlighter pens” to mark up the cookbooks. They do not change the recipes themselves, but their marks tell the body’s “chefs” which recipes to read, which ones to ignore, and how brightly to turn up the “light” on each one.
• The gene affected in Weaver syndrome is responsible for making a master “dimmer switch” protein. The primary job of this protein is to go around and turn down or off the activity of many other genes, especially those involved in growth.
• In Weaver syndrome, this dimmer switch is broken. It cannot properly turn down the growth signals at the right time during development.
• As a result, the “growth lights” are left on too bright for too long. This results in accelerated bone growth and other widespread developmental changes that are the hallmark of the syndrome.

In my experience, Weaver syndrome often presents as rapid early growth and developmental delay, which can lead parents to believe their child is simply “big for their age” until other features emerge.

The cause of Weaver syndrome is a mutation in the EZH2 gene. The EZH2 gene contains the precise genetic instructions for making a protein called a histone methyltransferase. This protein is the “dimmer switch” from our analogy. It is a key epigenetic regulator that works by adding a small chemical mark (a methyl group) to histones, which are the spool-like proteins that DNA is wound around. This mark typically acts as a signal to silence or turn off the expression of targeted genes.

When there is a mutation in one copy of the EZH2 gene, the body cannot produce enough of this functional “dimmer switch” protein. This failure to properly suppress the activity of numerous growth-related genes during development is what leads to the overgrowth and other characteristic features of Weaver syndrome.

In my experience, Weaver syndrome is present from birth and not something acquired later in life, it’s usually first noticed due to unusual physical growth or delayed milestones.

Weaver syndrome is a genetic disorder, but it is almost always the result of a new, random genetic change. It is not contagious.

• Sporadic (de novo) Mutation: In the vast majority of all documented cases, Weaver syndrome is caused by a de novo (new) mutation. This means that the mutation in the EZH2 gene is a random error that occurred for the first time in that individual, either during the formation of the egg or sperm cell of a parent, or very early after fertilization. In these cases, the parents have normal genes, and there is nothing they did or did not do to cause the condition. The risk of these parents having another child with Weaver syndrome is extremely low.
• Autosomal Dominant Inheritance: Because the condition is caused by a mutation in just one copy of the EZH2 gene, it is an autosomal dominant condition. This means that in the extremely rare case where an individual with Weaver syndrome has children, they will have a 50% chance of passing the condition on to each of their children.

In my experience, families are often surprised to learn the condition is linked to a single gene mutation, even when there’s no family history because many cases occur de novo.

The clinical features of Weaver syndrome can be variable, but there is a recognizable pattern of signs and symptoms.

Growth and Skeletal Features

• Overgrowth: This is the defining feature.
  • Children are often larger than average at birth (macrosomia).
  • They experience accelerated growth throughout childhood, making them significantly taller and heavier than their peers.
  • Head size is also typically large (macrocephaly).
• Advanced Bone Age: This is a key diagnostic feature. An X-ray of the hand and wrist will show that the bones are more mature and developed than what is expected for the child’s chronological age.
• Skeletal Abnormalities:
  • Camptodactyly: The fingers or toes are held in a permanently bent position.
  • Broad thumbs.
  • A small, recessed chin (micrognathia).
  • Spinal curvature (scoliosis or kyphosis).
  • A funnel-shaped chest (pectus excavatum).

Distinctive Facial Features

Many children with Weaver syndrome share a characteristic facial appearance.

• Widely spaced eyes (hypertelorism).
• Wide forehead and flat back of head.
• Large, low-set ears.
• A long, prominent philtrum (the groove between the nose and the upper lip).
• A small chin that is tucked back.

Neurological and Developmental Features

• A Hoarse, Low-Pitched Cry: This is a very characteristic sign in infancy.
• Hypotonia: Low muscle tone, or “floppiness,” is very common in infancy and early childhood. This can lead to significant feeding difficulties.
• Developmental Delay: Most individuals with WSS have some degree of developmental delay. Motor milestones like sitting and walking are often delayed due to hypotonia.
• Intellectual Disability: The degree of intellectual disability is variable but is typically in the mild to moderate range.

Clinically, I look for signs like advanced bone age, camptodactyly (bent fingers), large ears, and hypotonia, some children may also have behavioral or learning difficulties

The diagnosis of Weaver syndrome can be challenging because it is rare and its features can overlap with other overgrowth syndromes. The diagnostic process is typically managed by a clinical geneticist.

• Key Clinical Distinction: Weaver vs. Sotos Syndrome: Weaver syndrome can look very similar to another overgrowth disorder called Sotos syndrome. In the past, it was very difficult to distinguish them. Sotos syndrome is also characterized by overgrowth, advanced bone age, and developmental delay. However, children with Sotos syndrome tend to have a different facial appearance, with a prominent, elongated chin.
• Clinical Suspicion: A doctor will suspect an overgrowth syndrome based on the pattern of accelerated growth, large head size, advanced bone age on an X-ray, and the presence of characteristic facial features.
• Molecular Genetic Testing: Today, the definitive diagnosis is made with a molecular genetic test from a blood sample.
  • A doctor will typically order a broad genetic test, such as Whole Exome Sequencing (WES) or a specific overgrowth gene panel.
  • This testing analyzes the patient’s DNA and can identify a disease-causing mutation. A confirmed mutation in the EZH2 gene establishes the diagnosis of Weaver syndrome, while a mutation in the NSD1 gene would diagnose Sotos syndrome.

Once a diagnosis is confirmed, a child will undergo a comprehensive evaluation to screen for any associated health issues, which may include an echocardiogram (heart ultrasound), a renal ultrasound, an eye exam, and a formal developmental assessment.

In my experience, early diagnosis helps families understand the prognosis and access early intervention services for developmental support.

There is no cure for the underlying genetic cause of Weaver syndrome. Therefore, management is entirely supportive and symptomatic. The goal is to address each child’s specific medical and developmental needs with a proactive and coordinated approach. This requires a multidisciplinary team of specialists.

The key management strategies include:

• Early Intervention Therapies: This is the absolute cornerstone of management for a child with Weaver syndrome. Starting therapies as early as possible is crucial for helping a child achieve their maximum developmental potential.
  • Physical Therapy is vital for addressing the low muscle tone, improving motor skills and coordination, and preventing joint problems.
  • Occupational Therapy helps with fine motor skills, sensory integration, and learning the skills needed for daily activities like feeding and dressing.
  • Speech and Language Therapy is essential to address any communication delays.
• Nutritional Support: In infancy, a feeding therapist or nutritionist may be needed to manage feeding difficulties associated with hypotonia.
• Orthopedic Care: Regular monitoring by an orthopedic specialist is needed to watch for and manage the development of scoliosis or other skeletal issues.
• Educational Support: Children with Weaver syndrome will require an individualized education plan (IEP) and a supportive school environment to address their unique learning needs.
• General Medical Care: This includes regular check-ups with a pediatrician, routine vision and hearing screenings, and dental care.
• Cancer Surveillance: While some overgrowth syndromes are associated with a slightly increased risk of certain childhood tumors, the exact risk for individuals with Weaver syndrome is still being determined and is thought to be small. Your genetics team will discuss the most current recommendations for surveillance, which may include regular physical exams and abdominal ultrasounds.

Clinically, I focus on supportive care tailored to the individual’s symptoms, as there’s no cure, close follow-up helps address joint issues, delayed milestones, and educational needs.

A diagnosis of Weaver syndrome can be an overwhelming experience for a family, often coming after a long search for answers to explain their child’s unique developmental path. This rare genetic disorder, caused by a mutation in the master-control EZH2 gene, presents a lifetime of challenges related to overgrowth, skeletal health, and development. While there is no cure that can alter the genetic blueprint, a definitive diagnosis provides a crucial framework for understanding and support. The focus of care is not on a cure, but on proactive management. A dedicated, multidisciplinary team, working in partnership with the family, can address the medical and developmental needs of the child. Clinically, I’ve seen that although challenges vary, supportive care and individualized education plans make a significant difference in quality of life for children with Weaver syndrome.

National Organization for Rare Disorders (NORD). (2022). Weaver Syndrome. Retrieved from https://rarediseases.org/rare-diseases/weaver-syndrome/

National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2023). Weaver syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/7872/weaver-syndrome

National Center for Biotechnology Information. (n.d.). Weaver syndrome. U.S. National Library of Medicine. Retrieved July 8, 2025, from https://www.ncbi.nlm.nih.gov/medgen/120511