OMIM ID:
Epileptic Encephalopathy, Early Infantile 28
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Infants with this lethal neuropathy often have minimal or absent eye contact from birth. Responses to visual stimuli are often but not always absent. Optic atrophy may be present and the ERG is abnormal in some individuals. The retinas may have “abnormal” pigmentation while scotopic and photopic flash ERG responses are reduced as are visual evoked potentials indicating delayed visual maturation with severe macular and optic nerve dysfunction.
Systemic Features
Seizures begin within weeks after birth and are resistant to pharmacological treatment. There is no spontaneous motility and little or no psychomotor development. Normal developmental milestones are usually not achieved. Spasticity and hyperreflexia are often present but some newborn infants are hypotonic. MRI imaging reveals cortical atrophy with hippocampal hypoplasia and a hypoplastic corpus callosum. Progressive microcephaly has been described.
Infants generally do not live beyond two years of age and may die within weeks or a few months. Pulmonary dysfunction can be a significant cause of morbidity.
Genetics
Inheritance
The transmission pattern is consistent with autosomal recessive inheritance. Homozygous and compound heterozygous mutations in the WWOX gene (16q23) have been found in several families.
Among the limited number of patients reported, at least two with compound heterozygous mutations had normal brain imaging, appropriate visual responses, and some ability to interact with their environment. Profound psychomotor delays, however, remained. Hypotonia replaced spasticity as a neurological feature in some infants.
The same gene is mutated in autosomal recessive spinocerebellar ataxia 12 (614322), a less severe condition in which gaze-evoked nystagmus occurs.
Other forms of epileptic encephalopathy have been reported (see 617105, 617106, and 617113) including Early Onset Epileptic Encephalopathy 48 (617276). For an autosomal dominant form of epileptic encephalopathy in this database, see Epileptic Encephalopathy, Early Onset 47 (617166).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.