The clinical presentation and evolution of epileptic encephalopathy associated with a loss-of-function mutation in the phospholipase C-b 1 gene are reported in a male infant with infantile spasms treated at the University of Birmingham School of Medicine, UK. The infant’s parents were consanguineous. He presented with eye rolling, lip smacking, tonic stiffening and flexion seizures at 10 weeks, and subsequently developed infantile spasms and hypsarrhythmia at 8 months of age, associated with severe neurological regression (West syndrome). Spasms were refractory to a 2-week course of vigabatrin but were controlled with a course of prednisolone (ACTH was declined). At 10 months he developed tonic-clonic seizures resistant to AEDs and at 13 months, the EEG showed generalized slowing, consistent with diffuse encephalopathy. MRIs at ages 5 and 13 months were normal. His head circumference was at the 0.4th centile at birth and at 2.5 years, when he was functioning at 0-3 month level and was unable to lift his head when prone or roll over. At 2.9 years he had spastic quadriparesis, he contracted adenovirus pneumonitis and died of respiratory failure. Post-mortem was not performed. Molecular genetic analysis of the index case revealed a homozygous deletion on chromosome 20 involving the phospholipase PLCB1 gene. Linkage to the phospholipase C-b 1 locus was absent in 12 other consanguineous families of children with infantile spasms. The findings were consistent with genetic heterogeneity in infantile spasms. This is the first loss of function PLCB1 mutation described in humans. [1]

COMMENT. Infantile spasms and West syndrome is a heterogeneous disorder with cryptogenic and symptomatic etiologies. Genetic causes for West syndrome listed by the authors include mutations of ARX, controlling development of g-aminobutyric acid-ergic interneurons, mutations in STXBP1 (in Ohtahara and West syndromes), and deletions involving MAG 12. Phospholipase B-b 1 gene is involved in hippocampal muscarinic acetylcholine receptor signaling and in cortical development. The discovery of this mutation uncovers a novel mechanism for early-onset epileptic encephalopathy, infantile spasms and West syndrome.