You May Also See
Weaver Syndrome
A genetic overgrowth syndrome with advanced bone age, intellectual disability, and distinctive facial features.
Overview
Weaver syndrome is a rare genetic disorder characterized by rapid growth beginning before birth, distinctive craniofacial features, skeletal abnormalities, and varying degrees of intellectual disability. First described by Dr. David Weaver in 1974, the condition is also known as Weaver-Smith syndrome. Children with this syndrome often present with tall stature, advanced bone age, hypotonia (reduced muscle tone), and delayed developmental milestones. Although it shares some clinical similarities with other overgrowth syndromes, such as Sotos syndrome, Weaver syndrome has distinct genetic and phenotypic features that warrant separate classification.
Causes
Weaver syndrome is primarily caused by mutations in the EZH2 gene located on chromosome 7q36.1. The EZH2 gene provides instructions for making a protein that plays a critical role in regulating gene expression, cell division, and growth by modifying chromatin structure. Mutations in this gene lead to dysregulated gene activity during fetal development, resulting in abnormal growth and neurological outcomes.
The condition follows an autosomal dominant inheritance pattern, which means one copy of the mutated gene is enough to cause the disorder. However, most cases arise from de novo (new) mutations, meaning they occur spontaneously without a family history. Rarely, the condition can be inherited from a mildly affected parent.
Symptoms
The signs and symptoms of Weaver syndrome can vary among affected individuals but generally include a combination of growth abnormalities, facial features, neurological findings, and skeletal changes. Common clinical features include:
Pre- and postnatal overgrowth: Increased weight and length are often observed at birth and continue during infancy and early childhood.
Advanced bone age: Radiographic imaging reveals that bone maturation occurs faster than normal for the child’s chronological age.
Characteristic facial features: Including a broad forehead, hypertelorism (wide-set eyes), a prominent philtrum, a pointed chin, and large, low-set ears.
Hypotonia: Reduced muscle tone contributes to delayed motor development, such as late sitting, walking, or crawling.
Joint laxity or contractures: Affected individuals may have flexible joints or limited range of motion in certain areas.
Intellectual disability: Ranges from mild to moderate, often accompanied by speech delay and learning difficulties.
Cranial anomalies: Some individuals exhibit macrocephaly (large head circumference) and occasionally hydrocephalus (fluid accumulation in the brain).
Additional features that may be present include cryptorchidism in males, scoliosis, feeding difficulties, and minor congenital heart defects.
Diagnosis
Diagnosis of Weaver syndrome is based on clinical findings, family history, and confirmed through genetic testing. Because the condition overlaps with other overgrowth syndromes, careful differential diagnosis is necessary. Diagnostic steps include:
Physical examination: Evaluation of growth patterns, craniofacial structure, and developmental milestones.
Radiological imaging: X-rays are used to assess bone age and detect skeletal anomalies such as advanced ossification or scoliosis.
Developmental assessment: Formal evaluation of motor, cognitive, and speech development.
Genetic testing: Sequencing of the EZH2 gene to identify pathogenic variants that confirm the diagnosis.
Differential diagnosis: Conditions like Sotos syndrome or Beckwith-Wiedemann syndrome may present similarly and should be ruled out.
Treatment
There is no cure for Weaver syndrome, and treatment is focused on managing symptoms and promoting optimal development. A multidisciplinary care team is often required, including specialists in pediatrics, neurology, orthopedics, genetics, and developmental therapy. Key management strategies include:
Physical and occupational therapy: Helps improve muscle tone, motor coordination, and daily functioning.
Speech therapy: Addresses communication difficulties and supports language development.
Educational support: Individualized education programs (IEPs) may be necessary for children with learning disabilities.
Orthopedic interventions: Monitoring and managing joint issues, scoliosis, or contractures as the child grows.
Regular monitoring: Routine evaluations of growth, development, and potential complications such as hydrocephalus or cardiac anomalies.
Genetic counseling: Recommended for families to understand inheritance patterns and recurrence risks.
Prognosis
The long-term outlook for individuals with Weaver syndrome varies depending on the severity of symptoms and the degree of developmental delay. Most affected individuals reach adulthood and can live relatively independent lives with appropriate interventions. Intellectual disability is usually mild to moderate, and with early therapy, many children achieve significant developmental gains. Physical overgrowth tends to stabilize after early childhood, and advanced bone age may normalize with time. Early diagnosis and coordinated care play a crucial role in improving quality of life and overall prognosis for individuals with Weaver syndrome.
Medical Disclaimer
The information provided on this page is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.