Weaver Syndrome

Weaver syndrome is a rare disorder. Let's take a look at its characteristics, causes and treatment options.

Reviewed and approved by el médico Diego Pereira.

Written by Josberth Johan Benitez Colmenares

Last update: 02 July, 2023

Weaver syndrome is the name given to a series of rare congenital anomalies that are characterized by accelerated growth. Also called Weaver-Smith syndrome or EZH2-related overgrowth, it occurs in both men and women and some cases have shown parent-to-child transmission.

This was first described in 1974 by David Weaver. Since then, just over 50 cases have been reported in medical literature, so it’s a rare and largely unknown condition. Despite the limitations around it, we’re going to tell you what experts know about its characteristics and its causes.

Weaver syndrome symptoms

The syndrome is characterized by manifesting rapid bone growth and development. Because of this, those who develop it share some of the following distinctive features:

• Macrocephaly (then abnormal growth of the head circumference)
• Widened distal long bones
• Prominent chin crease
• Big ears
• Camptodactyly (interphalangeal flexion contracture)
• Hypertelorism (distance between the eyes longer than normal)
• Long philtrum (nasolabial fold)
• Hypertonia in the arms and legs (resistance to muscle mobilization)
• Hypotonia in the muscles of the torso
• Retrognathia (mandible behind the maxilla)
• Epicanthic folds
• Downward drooping eyelids

Other characteristics of people with the syndrome are fine hair, inverted nipples, loose skin, a round face, squint, thin or sunken fingernails, short ribs, a hoarse and low-pitched voice, excessive appetite, intellectual disability, and delayed speech. Most of these symptoms manifest in the first 5 years of age.

Causes of Weaver syndrome

As experts point out, Weaver syndrome is considered a variant of Marshall-Smith syndrome, although not everyone considers it as such. It also shares some similarities with Sotos syndrome, although they’re different conditions. The syndrome is a genetic disease, so it’s caused by one or more genes that don’t work correctly.

In principle, mutations in the EZH2 gene have been identified as the main culprits for the development of the syndrome. The same has also been done with the EED and SUZ12 genes. Mutations are sporadic, but cases have been reported due to autosomal dominant inheritance. Not all patients studied report genetic mutations of this type.

The function of the EZH2 gene is to turn other genes on and off through a process known as methylation. The influence of this on other genes explains why the syndrome is characterized by an alteration in many of the body’s systems. It isn’t known how these mutations occur or what other factors influence the process.

Diagnosis of Weaver syndrome

The syndrome overlaps with others such as Marfan syndrome, Imagawa-Matsumoto syndrome, Cohen-Gibson syndrome, Perlman syndrome, Beckwith-Wiedemann syndrome, the aforementioned Sotos syndrome, and excessive growth due to excess growth hormone. Differentiating one from the other isn’t always easy, although genetic testing can help diagnose abnormalities in the EZH2 gene.

During diagnosis, a variety of tests will be carried out to determine possible underlying problems with the heart, hands, feet, brain, muscles, and more. Based on the results, other evaluations will be made to determine the impact of the syndrome. Keep in mind that the symptoms vary in intensity in each patient, as well as their presence.

Treatment options

There’s no cure for Weaver syndrome. Currently, available therapies consist of symptom management and systemic support. Life expectancy is normal for most of them, and some interventions can help improve general well-being.

For example, physiotherapy can be an option to deal with muscle stiffness, and also to alleviate problems in the hands and feet. Psychological interventions are also useful in addressing the emotional and behavioral disorders associated with the syndrome. In some settings, surgery may be considered to reverse structural problems.