Epileptic Encephalopathy, Early Infantile, 23

A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-23 (EIEE23) is caused by compound heterozygous mutation in the DOCK7 gene (615730) on chromosome 1p31.

For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see 308350.

Clinical Features

Perrault et al. (2014) reported 3 girls from 2 unrelated nonconsanguineous families with EIEE. The girls were 5 to 10 years of age at the time of the report. All developed intractable seizures between 2 and 6 months of age. EEG showed multifocal epileptic activity in all, with 1 patient having at least 1 episode of hypsarrhythmia. In the first months of life, all girls showed delayed psychomotor development and cortical visual impairment or blindness. They had either poor speech or lack of speech and difficulties in activities of daily living, such as self-feeding. Dysmorphic features in the sisters included low anterior hairline, periorbital fullness, telecanthus, and broad nasal bridge with anteverted nares. The unrelated girl had bitemporal narrowing, low anterior hairline, thick and duplicated eyebrows, synophrys, long eyelashes, enophthalmia, a large prominent nasal root with bulbous tip, short philtrum, full lips, and abnormal ears. Brain imaging in 2 unrelated girls showed an abnormally marked pontobulbar sulcus with mild pontine hypoplasia and T2-weighted white matter abnormalities with atrophy in the occipital white and gray matter. All also had a thin corpus callosum.

Inheritance

The transmission pattern of EIEE23 in the families reported by Perrault et al. (2014) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 3 girls from 2 unrelated families with early infantile epileptic encephalopathy, Perrault et al. (2014) identified 4 different compound heterozygous truncating mutations in the DOCK7 gene (615730.0001-615730.0004). The mutations were found by exome sequencing and were predicted to result in a loss of protein function. Perrault et al. (2014) noted that since DOCK7 plays a role in neurogenesis, the regulation of neuronal polarity, and the development of GABAergic neurons, disruption of DOCK7 function could result in a neurodevelopmental disorder, as observed in their patients.