CASE REPORT
We report on a 16-year-old boy, referred to our department for afebrile unprovoked seizures. He was born at term by spontaneous vaginal delivery, of healthy unrelated parents, and with uneventful perinatal and postnatal clinical course. He did not experience febrile convulsions, traumatic brain injury, or central nervous system infections. Over time he was found to have a mild global learning difficulty that improved over time with occupational therapy. He was reported by the parents to be a very shy, quite timid, reticent, and solitary person. Also, stereotype and behavioral changes were noted. Emotional and social difficulties were reported by the family. During clinical assessment, craniofacial dysmorphic features of KBG syndrome were noted. Regarding the neurologic and behavioral aspects, the patient had mild intellectual disability, learning difficulties, and neurobehavioral problems such as attention deficit hyperactivity disorder (ADHD) since childhood. However, he was able to participate in normal school life without any help.
Targeted exome sequencing (TES) of 4800 clinically significant genes was performed and a pathogenic heterozygous variant, NM_001256183.2: c.4407dupG, frameshift, was identified in ANKRD11, c.4407dupG, (p. Arg1470GlufsTer84). As the parental genetic tests revealed that the parents did not have this frameshift, the variation was identified as a de novo variant. This variant was categorized as pathogenic by the American College of Medical Genetics and Genomics (ACMG) guideline (PVS1, PS1, PS2, and PM2) and has not been reported earlier. The variant is absent from control sequences (Genome Aggregation Database (gnomAD) and no alternative plausible variants or known mutations were identified as competing possibilities in this patient.