Clinical features
The main clinical features of the CYFIP2-related neurodevelopmental disorder are:
• Developmental delay / intellectual disability (100%)
o severe in the majority (70%) but can be mild
• Muscle tone anomalies (hypotonia, spasticity) (80%)
• Epilepsy (77%) with neonatal or childhood onset, often therapy-resistant
• Behavioral problems (56%)
• Visual problems (54%)
• Feeding issues (50%)
• Secondary Microcephaly (48%)
• Unspecific brain MRI anomalies (44%)
• Sleep disorder
Penetrance
The penetrance for pathogenic variants is likely 100%.
Variable Expressivity
The severity of these clinical features and the occurrence of additional clinical features is variable among individuals with CYFIP2-related neurodevelopmental disorders. Patients with the recurrent missense variants at p.Arg87 show a consistently severe phenotype of developmental and epileptic encephalopathy. However, for other CYFIP2 variants it is not possible to predict the degree of intellectual disability or which additional clinical manifestations a patient will develop.
CYFIP2