A case of isodicentric chromosome 15 presented with epilepsy and developmental delay
A 10-month-old female infant was referred to our pediatric neurology clinic for uncontrolled seizures and global developmental delay. She was born at term with normal birth weight (2,900 g) after a normal pregnancy and delivery. Her mother did not take any medications during pregnancy. At birth, her mother was 38 years old and her father was 39. Her older brother was healthy. There were no other family members with neurodevelopmental disorders. At the time of the referral, she could not control her head nor follow moving objects. The head circumference, height, and weight were all below the 3rd percentile. A physical examination was rather unspecific, and might include: minor facial dysmorphisms, such as frontal bossing, wide-set eyebrows, down-slanting palpebral fissures, low-set ears, highly arched palate, broad nose, short philtrum, strabismus, and generalized hypotonia. A metabolic evaluation (that included urine organic acids, serum amino acids, and a thyroid function tests) was normal. A brain magnetic resonance imaging showed mild brain atrophy. She suffered from generalized tonicclonic or generalized tonic seizures from the age of 7 months. Video-electroencephalography (EEG) monitoring was conducted at the age of 11 months and 25 months. At the first monitoring, brief tonic extension of both arms and legs were accompanied by ictal EEG pattern which showed mild diffuse attenuation of background activities with low amplitude rhythmic theta activities. At the second monitoring, clusters of extensor spasms were accompanied by ictal EEG which showed diffuse delta bursts followed by electrodecremental response. Video-EEG monitoring results were consistent with generalized tonic seizures and epileptic spasms. At the age of 6 years, she has been seizure free for 3 years after receiving valproate, topiramate, and lamotrigine. However, her developmental status has not improved and she still presents hand stereotypy, bruxism, and episodic tonic posturing.\nRoutine karyotyping revealed the presence of a supernumerary marker chromosome of the unknown origin (47, XX, +mar) (). Her parent's karyotypes were normal. Array comparative genomic hybridizations were performed using a Human Genome CGH Microarray Kit 180K, using an Agilent Oligo Array-CGH Hybridization Kit (Agilent Technologies, Palo Alto, CA, USA). Images of the arrays were acquired using a high-resolution microarray scanner (Cat. no. G2565CA, 2008, Agilent Technologies), and image analysis was performed using the genomic workbench standard edition 5.0 (ver. 5.0.14, 2009, Agilent Technologies). The result revealed amplification from 15q11.1 to 15q13.1 spanning 8.47 Mb (). Subsequent FISH analysis confirmed that the amplified chromosomal region, detected by an array CGH, was localized to the supernumerary marker chromosome ().