From the Guidelines
Weaver syndrome is a rare genetic disorder characterized by overgrowth, distinct facial features, and variable cognitive disability, caused primarily by heterozygous missense mutations in the EZH2 gene. The syndrome is associated with a range of physical and developmental characteristics, including tall stature, hypertelorism, broad forehead, almond-shaped eyes, pointed chin with horizontal crease, large and fleshy ears, doughy skin, camptodactyly, poor coordination, umbilical hernia, hoarse cry, advanced bone age, and hyper- or hypotonia 1. While individuals with Weaver syndrome may be at increased risk for developing certain types of cancer, such as neuroblastoma, the absolute risk is currently unknown and routine surveillance is not recommended 1. Instead, clinical vigilance and workup of potential tumor-related symptoms, especially for neuroblastoma, are suggested 1.
Key characteristics of Weaver syndrome include:
- Overgrowth and tall stature
- Distinct facial features, such as hypertelorism and broad forehead
- Variable cognitive disability
- Doughy skin and camptodactyly
- Poor coordination and umbilical hernia
- Advanced bone age and hyper- or hypotonia
- Potential increased risk for certain types of cancer, such as neuroblastoma 1
Management of Weaver syndrome focuses on managing symptoms and supporting development, rather than curing the condition. This may involve physical therapy, speech therapy, educational support, and regular medical monitoring to address any related health complications 1.
From the Research
Definition and Characteristics of Weaver Syndrome
Weaver syndrome is a rare autosomal dominant disorder characterized by:
- Distinctive facial features, including ocular hypertelorism, broad forehead, almond-shaped palpebral fissures, and large, fleshy ears in early childhood 2
- Pre- and post-natal overgrowth, macrocephaly, and variable developmental delay 2, 3
- Tall stature, reported in >90% of affected individuals 4
- Intellectual disability, present in ~80%, but highly variable and frequently mild 4
Genetic Causes
The syndrome is caused by heterozygous pathogenic/likely pathogenic variants in the:
- Enhancer of zeste homolog 2 (EZH2) gene 2, 4
- EED gene, which is associated with locus heterogeneity in Weaver syndrome 5
Clinical Features and Diagnosis
Additional clinical features that may help in diagnosing Weaver syndrome include:
- Camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry 4
- Characteristic facial features, which can be subtle and challenging to diagnose, especially in older individuals 4, 6
- The diagnosis may be more difficult to make in adolescents and adults if one uses criteria developed for facial manifestations in young children 6