Clinical Characteristics

Patients with RHOBTB2 mutation are mainly diagnosed as developmental and epileptic encephalopathy with or without movement disorders. Some patients show movement disorders without epilepsy. A few patients may be diagnosed as Rett syndrome or Pitt-Hopkins syndrome. Episodes of acute encephalopathy, such as sudden onset of seizures, disturbed consciousness, and hemiparesis, are also seen in half of the patients.

The first symptom is seizure attacks in most patients, starting mainly less than 1 year of age. Development before seizures is usually normal.

Focal seizures or focal to bilateral tonic-clonic seizures are more frequent than generalized seizures. Half of the patients with seizures show status epilepticus lasting more than 5 minutes. Fever-induced seizures are also common. Outcome of seizures are variable in each patient. Some patients show good response to anti-seizure medications, some show poor response, and some are naturally resolved. Worsening of neurological deficits mainly correlating with epilepsy can be seen.

Intellectual disability is commonly seen. Two thirds of the patients show very severe or severe intellectual disability. Motor ability is also damaged, but half of the patients can walk alone or with support.

A variety of movement disorders, such as dystonia, ataxia, chore, dyskinesia, and stereotypic hand movement, are frequently seen. Acute encephalopathic episodes are seen in half of the patients. Three patients have episodes of minor head trauma  prior to encephalopathy.

Microcephaly appears in half of the patients.

Brain MRI is normal in the beginning, then the brain gets smaller in some patients. Autonomic signs, such as skin color change, or abdominal symptoms, are seen in some patients.