Whole-exome sequence sometimes may be the only diagnostic method in infantile spasms

Abstract

Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown ethology in ∼40% of patients. Unexplained IS cases represent a large collection of rare single-gene disorders. Eight-year-old female patient which is a fourth child from consanguineous marriage was referred to our clinic because of epilepsy and psychomotor retardation. She was diagnosed with West syndrome when she was 6 months old. Neurological examination showed evident hypotonia, increased deep tendon reflexes and spasticity. Routine laboratory (complete blood count, clinical chemistry) and metabolic tests (tandem mass spectrometry, blood, urine and cerebrospinal fluid amino acids and urine organic acid, ammonia, lactate, pyruvate) and cranial MRI were normal. Whole-exome sequence (WES) revealed heterozygous de novopathogenic variant in ALG13 gene. It was determined that the parents were normal in terms of this mutation. IS are genetically heterogeneous due to the major role of de novopathogenic variants in genome, and sometimes WES may be the only diagnostic method.