Weaver syndrome is a rare, congenital genetic condition characterized by accelerated growth. This rapid growth often begins before birth, causing children to be significantly taller and larger than their peers, which is a primary indicator of the disorder.
Key Physical and Developmental Characteristics
The accelerated growth of Weaver syndrome can be observed before birth on prenatal ultrasounds, with newborns often having a higher birth weight and length. This leads to a tall stature and advanced bone age, where a child’s skeletal maturity is greater than their chronological age. Another sign is macrocephaly, an unusually large head size.
Distinctive facial features are common, and many infants have a characteristic low-pitched, hoarse cry. These features can include:
- A broad forehead
- Wide-set eyes (hypertelorism)
- A long groove between the nose and upper lip (philtrum)
- A small or recessed chin
- Large ears
- Down-slanting eyelid folds
Skeletal and muscular systems are also affected. Individuals may have permanently bent fingers (camptodactyly), curvature of the spine (scoliosis), or joint contractures limiting movement. Low muscle tone (hypotonia) is a common neurological symptom that causes poor coordination and balance, leading to delays in motor milestones like sitting, standing, and walking.
Developmental effects vary, but many individuals experience a mild intellectual disability. The range of cognitive ability is broad. Speech delays and challenges with behavioral regulation are also common. The severity of all symptoms differs from one person to another.
The Genetic Basis of Weaver Syndrome
Weaver syndrome is caused by mutations in the EZH2 gene on chromosome 7. This gene provides instructions for making an enzyme that acts as a regulator, helping to control the activity of other genes by turning them “off.” When a mutation disrupts this function, it leads to the uncontrolled growth seen in the syndrome.
The condition follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene from a parent is needed. However, most cases result from a spontaneous de novo mutation. This means the genetic change occurs for the first time in the affected individual, with no family history of the disorder.
Because most mutations are spontaneous, parents of a child with Weaver syndrome usually do not carry the gene, and the risk of having another affected child is very low. Genetic counseling can provide families with more specific information.
Diagnosis Process
Diagnosing Weaver syndrome begins with a clinical evaluation by a physician or geneticist. The provider assesses the child for the combination of physical traits and developmental patterns associated with the disorder, such as a history of developmental delays.
A prenatal ultrasound may offer the first clues by showing longer-than-average bones for the gestational age. After birth, a physician might note the infant’s rapid growth and hoarse cry, though in some cases signs are not apparent for several months.
While clinical observations are suggestive, a definitive diagnosis requires molecular genetic testing. A blood test is used to analyze the individual’s DNA for a mutation in the EZH2 gene. Identifying a pathogenic variant confirms the diagnosis and helps distinguish Weaver syndrome from other overgrowth conditions with similar features, like Sotos syndrome.
Approaches to Management and Support
There is no cure for Weaver syndrome, so management focuses on addressing specific symptoms. A multidisciplinary team of specialists works together to create a personalized support plan to manage health issues and aid development throughout the individual’s life.
Physical and occupational therapies help manage the motor challenges of the condition. Physical therapy addresses low muscle tone (hypotonia), improves coordination, and manages skeletal issues like joint stiffness. Occupational therapy helps individuals develop skills for daily living, while speech therapy is recommended to address common speech delays.
Regular monitoring by various specialists is part of the management plan:
- Pediatricians and neurologists to track overall development and manage neurological symptoms.
- Orthopedic specialists to address skeletal abnormalities like scoliosis or joint problems.
- Individualized educational plans to provide tailored academic support for any learning disabilities.
- Clinical vigilance for any potential tumor-related symptoms.