A case of 15q11‐q13 duplication syndrome and literature review

Abstract Background The chromosomal 15q11‐q13 regions are structurally complex, and their abnormalities are associated with various neuropsychiatric disorders, including autism spectrum disorder (ASD), epilepsy, Angelman syndrome, and Prader–Willi syndrome. Case description A 6‐year‐old child was admitted to the hospital as a result of an “epileptic status” showing ASD, intractable epilepsy, and total developmental retardation. Chromosome gene detection showed repetitive variation in the 15q11‐q13 regions, and the video electroencephalogram was abnormal. Although children are currently given antiepileptic treatment and rehabilitation training, intermittent seizures can still occur. Conclusion The clinical phenotypes of 15q11‐q13 repetitive syndrome are complex, and vary in severity. Children with intractable epilepsy, ASD, and language and motor retardation should be considered to have this syndrome, which requires confirmation by multiplex ligation‐dependent probe amplification and gene detection. These approaches can enable early rehabilitation treatment and improve the patients’ quality of life.


INTRODUCTION
Overall, 15q11-q13 repetitive syndrome is an autosomal dominant genetic disorder characterized by different clinical manifestations based on the individual. The common manifestations include developmental retardation, hypotonia, bradykinesia, mental retardation, epilepsy, and autism spectrum disorder (ASD). Autism spectrum disorder is a complex neurological disease characterized by social difficulties, language disorders, and repetitive and stereotypical behaviors.
Additionally, over 70% of children have mental retardation. Genetic This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC factors are important causes of autism, and include genetic mutations and chromosomal copy number variants (Bill & Geschwind, 2009).
Epilepsy is a common chronic nervous system disease that affects millions of people worldwide and often occurs in patients with chromosomal variants as well. Moreover, most patients with chromosomal variants develop language and motor retardation (Horsthemke & Wagstaff, 2008

Personal history
The boy was the first birth and first child of his mother; he was an easy delivery, but was overdue (45 +6 ). His birth weight was 3000 g. There was no history of asphyxia or hypoxia following birth. No abnormalities were found during the neonatal period. He was able to sit by month 8 and walk by month 17. He could shout "Mom" and "Dad" at 3 years old.
At the time of this study, he could speak complete sentences, but was unable to communicate normally with people.

Admission examination
No special examination is conducted.

Auxiliary examination
The blood, urine, and stool routines, myocardial enzyme level, liver and kidney function, cardiac color ultrasound, abdominal color ultrasound, head magnetic resonance imaging, urine organic acid analysis, blood amino acid, and carnitine analysis were all normal. The video electroencephalogram ( Figure 1) was abnormal for the child. Extensive/multifocal spike waves, slow spike waves, and multiple slow spike waves were emitted during each period. Sleeping discharge was in a nearly continuous state. Partial comprehensive secondary attacks were monitored in the right frontal pole and frontal region during the waking period. The above information was used in the clinical diagnosis of ASD. To date, the child has received oral administration of oxcarbazepine and lamotrigine, and has occasionally had seizures. Seizure frequency has been significantly reduced, and rehabilitation training has been carried out.

Returned results of Pediatric Cardiac Scale (2016)
After examination by medical ethics and family members using Agilent SurePrint G3 Human Genome CGH Microarray (array CGH) 8 × 60 K chip (Agilent Technologies, America) comparative genomic hybridization, follow the instructions. Luciferin (Cy3/Cy5) was applied to label the DNA of the patient and the reference samples, and then, microarray hybridization and post-hybridization washing were performed. Fluorescence images were obtained using an Agilent chip scanner, and the data were read by Feature Extraction Technologies; Repeated variation of exon1 of the MKRN3 gene was found at the site of 15q-cen in the subject's chromosomes; no large fragment variation was found at P106. The parents did not have the above variants. Considering the new variants, the child was diagnosed with 15q11-q13 repetitive syndrome.

DISCUSSION
A large number of low copy repeats (LCRs) exist in the 15q11-q13 The child subject discussed about in this study, had 15q11-q13 repetitive syndrome, which is characterized based on individual differences. He was treated in our hospital due to frequent seizures, which were followed by a post-epileptic status; the treatment outcome was poor, even after prescribing various antiepileptic drugs. The child also suffered from autism, and language and motor retardation. There are two mechanisms of 15q11-q13 repetition syndrome: the marker chromosome [inv dup(15)   genomic region may play a role in a dose-dependent manner, and the copy number of these genes may be significant in terms of brain development. Alterations in epigenetic regulation lead to abnormal gene expression (Horsthemke & Wagstaff, 2008;Roberts et al., 2002).

Hogart et al. analyzed the expression of different genes in 15q11-q13
hexasomy and tetrasomy in male brain tissue. They believed that alterations in genetic copies, as well as additional effects linked to heredity or environment on epigenetic mechanisms, may affect the outcome and clinical heterogeneity of 15q11-q13 repetitive syndrome (Hogart et al., 2009). Our case further demonstrated the phenotypic heterogeneity and clinical outcomes in this complex region.
Although epilepsy is a fairly common condition, not all patients with