Epileptic Encephalopathy, Early Infantile 28

Background and History: 

Many genes are involved in brain development and function.  When changed (mutated) their normal function can be altered resulting in neurological abnormalities.  Widespread changes in the brain are sometimes called encephalopathy. The condition described here is a severe and lethal form of neurological disease resulting from a specific mutation.  Delayed development, epilepsy, and mental retardation are common features.

Clinical Correlations: 

Seizures often have their onset within a few days or weeks after birth.  Infants do not make eye contact and they may lack the usual visual responses to environmental stimuli.  There is evidence from examinations of several babies that the optic nerve is damaged and the retina and its connections to the brain are not properly formed.

The epilepsy is difficult to control with medications.  Infants do not move properly and do not display the appropriate responses to handling and external stimuli.  The limbs are usually stiff.  Developmental milestones such as sitting, head-holding, and crawling are not achieved. They never learn to walk.  Brain scans (MRIs) reveal widespread underdevelopment of brain structures and the skull is often small.  Breathing problems secondary to lung disease may be a significant problem.

Genetics: 

This condition results from mutations in both copies of a specific gene.  Individuals such as the parents who carry a single mutated copy are clinically normal but each of their children has a 25% risk of inheriting the two abnormal copies.

Diagnosis and Prognosis: 

Infants may appear physically normal at birth but the occurrence of seizures and lack of normal neurological development should call attention to this condition within weeks.  Pediatricians and pediatric neurologists are likely to make the diagnosis while the medical eye doctor (ophthalmologist) can document the eye and optic nerve problems by examination and the results of an ERG (electroretinogram).

There is no known treatment.  A few individuals have lived up to two years of age but most die within weeks or a few months.

Additional Information
Inheritance/Pedigree: 
Autosomal recessive