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.