EAST Syndrome (Epilepsy, Ataxia, Sensorineural Deafness, and Tubulopathy)
The constellation of cerebral volume loss, seizures, edema, and deaf-mutism most closely describes EAST syndrome, a rare genetic disorder caused by mutations in the KCNJ10 gene, though MELAS syndrome should also be considered in the differential diagnosis when stroke-like episodes and lactic acidosis are present. 1, 2
Clinical Features of EAST Syndrome
Core Diagnostic Criteria
- Seizures: Generalized tonic-clonic seizures typically begin at 3-4 months of age as the first presenting symptom 1
- Ataxia: Non-progressive cerebellar ataxia that proves to be the most debilitating feature, with some patients becoming non-ambulant 2
- Sensorineural deafness: Develops after the initial seizure presentation 1, 2
- Tubulopathy: Renal salt-wasting tubulopathy with hypokalemic metabolic alkalosis 1, 2
Neuroimaging Findings
Brain MRI consistently reveals specific abnormalities that aid in diagnosis: 2
- Symmetrical hyperintensity signal changes in the cerebellar dentate nuclei (present in all available imaging) 2
- Corpus callosum hypoplasia (documented in four patients) 2
- Brainstem hypoplasia (documented in four patients) 2
- Small spinal cord (documented in three patients) 2
- Quantitative volumetric analysis confirms cerebral volume loss, particularly affecting the cerebellum, corpus callosum, and brainstem 1, 2
Differential Diagnosis: MELAS Syndrome
MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) must be excluded when evaluating this symptom complex, particularly if stroke-like episodes are present. 3
MELAS Diagnostic Criteria
The American Academy of Otolaryngology-Head and Neck Surgery identifies MELAS with the following features: 3
- Periods of confusion with elevated serum lactic acid levels during attacks 3
- Stroke-like episodes before age 40 years 4
- MRI white matter signal changes 3
- Migraine-like headaches 3
- Seizures 3, 4
- Diabetes mellitus 3
- Mitochondrial gene mutations (Mt-RNR1, Mt-TS1, POLG genes) 3
Key Distinguishing Features
Three invariant criteria secure the diagnosis of MELAS: 4
- Stroke-like episode before age 40 years 4
- Encephalopathy characterized by seizures, dementia, or both 4
- Lactic acidosis, ragged-red fibers on muscle biopsy, or both 4
The diagnosis is further supported by at least two of the following: 4
Management Approach for EAST Syndrome
Seizure Management
Carbamazepine is the most effective first-line agent for seizure control in EAST syndrome. 1
- Seizures are typically brief (<3 minutes) but status epilepticus can occur with medication withdrawal 1
- Alternative effective agents include lamotrigine, valproic acid, and topiramate 1
- Most patients achieve good seizure control with appropriate antiepileptic therapy 2
Genetic Testing
Molecular genetic testing should identify the homozygous c.170C>T (p.Thr57Ile) missense mutation in the KCNJ10 gene. 1
Prognosis
The neurological features of EAST syndrome are non-progressive, which is critical for counseling families. 2
- Ataxia remains the most debilitating long-term feature 2
- Seizures generally respond well to treatment 2
- Hearing loss requires audiologic support and possible hearing aids 3
Critical Pitfalls to Avoid
Do not confuse EAST syndrome with cerebellar mutism syndrome (CMS), which occurs postoperatively after posterior fossa surgery and presents with initially profound but reversible speech disorder. 5 CMS develops after surgical injury to bilateral efferent cerebellar pathways, whereas EAST syndrome is a genetic disorder present from infancy 5, 2.
Do not overlook the renal tubulopathy component, as electrolyte management is essential for preventing complications and may influence seizure control 1, 2.
Routine EEGs are typically normal or show only non-specific findings in EAST syndrome, so normal EEG does not exclude the diagnosis 1.