Impaired executive function, weak motor skills, and a rare form of epilepsy in an intellectually disabled girl with a 8q12.3q13.2 microdeletion

Abstract

Objective: Whole genome microarray techniques are the primary tool for the etiological assessment in intellectually disabled patients and have led to the discovery of several causative novel microdeletions. Participants and Methods: Extensive neuropsychological, neurological, psychiatric and genetic workup was performed in a 9-years-old female patient with a history characterized by delay of psychomotor and speech development, mild to moderate intellectual disability and persistent sleep disturbances since the age of two. Results: Besides lowered intelligence, impaired inhibitory control and executive function were found as well as weak language and motor skills. MRI-scanning of the brain revealed no abnormalities. EEG demonstrated frequent epileptiform activity centroparietal bilaterally with marked increase during sleep corresponding with continuous spike-waves during slow sleep (CSWS) syndrome, more specifically Electrical Status Epilepticus in Sleep (ESES). Several dysmorphic features were noticed including hypertelorism, downslanting palpebral fissures, a long, pear shaped nose, and low set, posteriorly rotated ears. Furthermore, she had a pectus excavatum, bilateral flat feet, and a sandal gap. Array-CGH demonstrated a 3.57 Mb de novo microdeletion in chromosome 8q12.3. Anti-epileptic treatment (sulthiame) resulted in a marked improvement of the patient’s sleep pattern and consequently of her behaviour. Conclusions: This de novo 8q12.3q13.2 microdeletion syndrome is characterized by a specific combination of neuropsychological dysfunction including impaired language and motor skills and a rare form of juvenile epilepsy (CSWS). Given the patient’s neuropsychological profile, it was advised to avoid overestimation of cognitive and language capacities, and to use educational and learning strategies based on modelling rather than on verbal instruction. Regular follow-up to monitor development by means of repeated neuropsychological assessments was planned.