EIF2AK2

Clinical Characteristics

The following description is based on the Mao et al., article published in the American Journal of Human Genetics in 2020.

Growth parameters
Majority of children with EIF2AK2 mutations have poor growth parameters, of which 2 of 8 reported had intrauterine growth retardation.

Head and facial features
Children were noted to have decreased head circumference, which is progressive in some individuals. Dysmorphic facial features are variable in patients and include short philtrum, hypotelorism, epicanthal folds, and micrognathia. Visual abnormalities include nystagmus, and astigmatism.

Skeletal features
Progressive contractures, fifth finger clinodactyly, and fifth toe clinodactyly were observed in some individuals.

Neurological features
Individuals with LEUDEN syndrome have global developmental delay, poor or absent speech, dysarthria, delayed walking, ataxia, episodic neurologic regression associated with fever or illness, loss of developmental milestones, and variable cognitive impairment. Some individuals have postural instability, dystonia, spasticity, hypotonia, hypertonia, extrapyramidal signs, parkinsonism, tremor, abnormal involuntary movements, and seizures.

MRI brain imaging findings include hypomyelination, delayed myelination, thin corpus callosum, cerebral atrophy, enlarged ventricles, cerebellar atrophy, thin brainstem and spinal cord involvement.