A 37-year-old woman, born in September 1977, first presented to our clinic in February 2015 because of severe aggressive outbursts. She was the only child of healthy, unrelated Caucasian parents with an unremarkable family history. She was born 3 days after the due date following an uneventful pregnancy with a birth weight of 3900 g (43rd centile) and a birth length of 52 cm (55th centile). Occipitofrontal circumference and Apgar scores were not reported. Cleft palate and craniofacial dysmorphic signs were noted at birth. She had problems with swallowing. She began sitting at 9 months and walked at 18 months. Her speech development was delayed; her vocabulary consisted of only a few words (mama, papa). She pointed with her hands to indicate what she wanted.
At the age of 6 years, the patient achieved a mental age of 3 years, with an intelligence quotient (IQ) in the mild mental retardation range (IQ 50-55) on the Wechsler Intelligence Scale for Children (WISC). She was hyperkinetic, with behavioural problems that were still manageable. She attended a special school, where she coped well with the programme. She learned to ride a tricycle. She had only a few, poorly-developed, protruding teeth.
At the age of 12 years, the patient's mental state deteriorated. She regressed to the level of severe mental retardation, achieving an IQ of 25-30 points on WISC. Her speech deteriorated and she was no longer able to speak any words. Her height was 142 cm (10th centile) and her weight was 37 kg (26th centile). She understood and carried out only very simple instructions and tasks. She disliked the company of children of her age, preferring the company of adults. Her hyperkinetic and behavioural problems increased at this time, together with auto- and heteroaggression. Left facial hypotrophy was evident, and her walk was rigid and broad-based. She was admitted to a care home for mentally handicapped children.
In May 2015, when she was last examined for this report, the patient's aggressive outbursts were even more frequent and persistent than they had been previously. Her behaviour was unpredictable, with shouting, throwing herself on the floor, hitting her head on the floor (causing nose bleeds), refusing to eat and being aggressive towards others. Swallowing problems were still present. Computed tomography scans, before and after the application of contrast media, revealed no abnormalities in the skull or brain matter. The patient was of normal height and weight; she had sparse hair, thin, pale skin, craniofacial dysmorphism (a long and asymmetric face, short and flat philtrum, and pointed chin), oligodontia and a left periorbital dermoid cyst (Figure 1). 
Molecular karyotyping was performed on this patient and her parents using DNA extracted from peripheral blood leukocytes with the QIAamp  DNA Blood Midi Kit (QIAGEN, Hilden, Germany). Analysis was carried out using the BlueGnome CytoChip ISCA 8x60K platform (Illumina UK, Cambridge, UK). The protocol was performed according to the manufacturer's instructions and data were analysed using the BlueFuse  Multi v3.1 software tool (Illumina UK). The deletion was confirmed using a paralogue ratio test (PRT) according to a previously described protocol. For this, a pair of oligonucleotides (identification number: chr2ppn1p449839453) was selected, which coamplify a region within the deletion (chr2: 196,578,414-196,578,640; 226 base pairs [bp]) and a reference region from chromosome 17 (chr17: 58,027,459-58,027,690; 231 bp).
Molecular karyotyping in this patient revealed an 8.6 Mb interstitial deletion of the chromosomal region on the long arm of chromosome 2, between 191,711,722 bp and 200,347,340 bp (GRCh37/hg19). The deletion lies within the chromosomal bands 2q32.22q33.1 and encompassed 22 known genes listed in the Online Mendelian Inheritance in Man (OMIM) database, including the GLS, MYO1B, TMEFF2, PGAP1 and SATB2 genes. The chromosomal position of the deletion in the present case is labelled red on Figure 2. Molecular karyotyping of the patient's parents did not show any aberrations. The PRT analysis showed an ~50% reduction in signal height for the chromosome 2 target locus (226 bp fragment) compared with the signal height from the reference 231 bp fragment from chromosome 17. Statistical analysis yielded a Z-score of 5.2 with a corresponding P-value <0.001. Thus, the PRT result confirmed the presence of copy number variation on chromosome 2 in this patient. 
Ethics approval for this analysis was obtained from the Republic of Slovenia National Medical Ethics Committee (NMEC), Ljubljana, Slovenia (NMEC 89/01/11). Written informed consent was obtained from the parents of the patient for publication of this case report and its accompanying images.