Unknown. ~100 cases have been reported but this may be an underestimate. Neonates with such a severe disease and early death may escape clinico-EEG diagnosis.

Age at onset
First hours and days of life.

Males = females.

Neurological and mental state

Multifactorial disease. Inborn errors of metabolism are the most common causes (non-ketotic hyperglycinemia, propionic aciduria, methylmalonic acidemia, D-glyceric acidemia, sulphite and xanthine oxidase deficiency, Menkes disease, Zellweger syndrome, and molybdenum co-factor deficiency). Metabolic causes explain the high incidence of siblings with this disorder. Lesional brain abnormalities are rare.

Clinical manifestations
A triad of intractable seizures. Erratic myoclonus appears first followed by simple focal seizures and later by tonic epileptic (infantile) spasms.

Erratic myoclonias shift typically from one part of the body to another in a random and asynchronous fashion. They are often restricted in a finger, a toe, the eyebrows, eyelids, or lips, occurring in the same muscle group and often migrating elsewhere. Myoclonias are brief, single or repetitive, very frequent, and nearly continuous.

Massive, usually bisynchronous, axial myoclonic jerks may start from the onset of the disease or occur later, often interspersed with erratic myoclonias.

Other type of seizures
Simple focal seizures (eye deviation or autonomic symptoms such as flushing of the face or apnea), focal clonic seizures of any part of the body, asymmetrical tonic posturing.

Tonic seizures occur frequently; epileptic spasms are rare and generally appear later.

Diagnostic procedures
Metabolic screening is mandatory and analysis consists of mainly serum levels of amino acids, particularly glycine and glycerol metabolites, organic acids, and amino acids in the cerebrospinal fluid (CSF). Brain imaging is usually normal at the onset of the disease but atrophy often develops.

Inter-ictal EEG
'Repetitive suppression-burst pattern' without physiological rhythms. This evolves to atypical hypsarrhythmia or multifocal spikes and sharp waves 3 to 4 months from onset of the disease.

Ictal EEG
Erratic myoclonias usually do not have an ictal EEG expression and may follow the bursts.

Poor. More than half of the patients die within weeks or months from onset, and the others develop permanent, severe mental and neurological deficits.

Differential diagnosis
The main differential diagnosis is from Ohtahara syndrome.

Management options
Seizures are refractory to treatments.

This section was adapted from: The educational kit on epilepsies, The epileptic syndromes By C. P. Panayiotopoulos Originally published by MEDICINAE 21 Cave Street, Oxford OX4 1BA First published 2006 and reprinted in 2007

Authored By: 
C. P. Panayiotopoulos MD, PhD, FRCP
Authored Date: 
Reviewed By: 
Steven C. Schachter MD
Sunday, June 1, 2008