Heterozygous deletion of exon 3 of phospholipase C β1 gene causes neonatal epileptic encephalopathy?

We report on a 3½-year-old patient, who was born in the 37th + 3 week of gestation by primary Caesarean sectio. Apgar values were 5/7/10, and the umbilical artery pH was 7.28. Postnatal temporary assistant ventilation by mask was necessary for a short period. There was a very fast recovery and the newborn initially stayed at the obstetric department. On the second day of life, generalized convulsions developed, with prolonged tonic, clonic, and myoclonic seizures, in series up to 1 hour duration. There was no effect of therapy with Phenobarbital and pyridoxine. Additional treatment with valproic acid led to a temporary stop of convulsions at the age of 15 days.

Detailed examination for inborn disorders of metabolism including determination of pipecolinic acid in serum and CSF, amino acids, and neurotransmitters in CSF revealed no abnormalities. In cerebral MRI, a discrete bleeding in the left ventricle was found. In the further course, epileptic clusters developed again. When Phenobarbital dosage was reduced at the age of 5 months, tonic seizures with bulbus deviation reoccurred. Valproic acid treatment was given continuously and beyond the age of 20 months no more seizures were observed. The infant shows a global severe psychomotoric developmental disorder with muscle hypotonia of the trunk, diplegia, and missing speech comprehension.

In array CGH, a 105.2-kb heterozygous deletion in 20p12.3 was detected, which included the region of the phospholipase C β1 (PCB1) gene. This deletion was confirmed by qPCR showing heterozygous deletion of exon 3 of the PCB1 gene. Sequencing of the PCB1 gene showed no additional mutation or deletion on the other chromosome. The parents do not show this deletion.

In 2010, Kurlan et al for the first time reported the association of early-onset pharmacoresistant epileptic encephalopathy and homozygous PCB1 deficiency. We suppose that the heterozygous deletion of exon 3 of the PCB1 gene in our patient may cause the neonatal epileptic encephalopathy.