Epileptic Encephalopathy, Early Infantile, 12
A number sign (#) is used with this entry because early infantile epileptic encephalopathy-12 (EIEE12) is caused by homozygous mutation in the PLCB1 gene (607120).
For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Clinical FeaturesKurian et al. (2010) reported a boy, born of consanguineous parents from Bangladesh, who presented with seizures at age 10 weeks. Seizures were characterized by eye rolling, lip smacking, drooling and perioral cyanosis followed by tonic stiffening and flexion of arms and legs. At age 8 months, he developed refractory seizures and regression in all areas of development. By 13 months, EEG showed features of West syndrome, hypsarrhythmia, and generalized slowing, consistent with a diffuse encephalopathic process. He had no meaningful development, with poor visual fixation, severe head lag, axial hypotonia, and spastic quadriparesis. He died of infection at age 2.9 years.
Poduri et al. (2012) reported a boy, born of consanguineous Palestinian parents, with EIEE12 manifest clinically as malignant migrating partial seizures in infancy (MMPSI). The patient had onset of focal seizures at age 6 months and thereafter showed developmental regression. Symptoms included perioral cyanosis, limpness, mouth automatisms, eyelid fluttering, and eye deviation. He had marked hypotonia, made only gutteral sounds, and did not fix or follow objects. EEG showed multifocal interictal spikes and abundant seizures arising from both hemispheres and showing migration from one hemisphere to another within a seizure. He had multiple seizures per day, and the seizures were refractory to treatment. Poduri et al. (2012) considered the disorder to be electroclinically distinct from that in the patient described by Kurian et al. (2010), who had a normal initial EEG and later developed hypsarrhythmia.
Molecular GeneticsBy genomewide scanning of a patient with early infantile epileptic encephalopathy, Kurian et al. (2010) identified a homozygous 0.5-Mb deletion on chromosome 20p12 encompassing the promoter element and exons 1, 2, and 3 of the PLCB1 gene (607120.0001), resulting in loss of PLCB1 expression. No other coding genes were involved in the deletion, which was not found in 660 control chromosomes. The telomeric and centromeric genomic breakpoints were mapped to 8,034,442-8,034,510 bp and 8,520,654-8,520,722 bp, respectively. Each unaffected parent was heterozygous for the deletion.
In a patient, born of consanguineous Palestinian parents, with EIEE12 manifest clinically as malignant migrating partial seizures in infancy (MMPSI), Poduri et al. (2012) identified a homozygous 486-kb deletion on chromosome 20p12.3 encompassing the promoter region and exons 1, 2, and 3 of the PLCB1 gene. The deletion breakpoints were mapped to 8,094,049-8,094,072 to 8,580,261-8,580,284 (GRCh37). The breakpoints lie within 2 LINE nuclear elements and likely arose from nonallelic homologous recombination.