Abstracts

Rationale: The deletion of the distal short arm of chromosome 12 are rare structural aberrations. The reported clinical manifestations in patients with 12p13.3 deletion were developmental delay/intellectual disability, facial dysmorphisms, and psychiatric problems. Methods: G-banded chromosome analysis was performed on peripheral blood lymphocytes according to standard techniques. A genomic microarray was performed using the SurePrint G3 Human CGH+SNP Microarray 4x180K kit (Agilent Technologies, Inc., Santa Clara, CA, USA), and no abnormalities were shown. Results: Case 1: The twelve-year-girl came to our hospital for status epilepticus and intellectual disability. The pregnancy was uneventful. Under phenobarbital and levetiracetam, epilepsy has been controlled. Brain magnetic resonance imaging (MRI) showed no obvious abnormalities with a normal myelination pattern. Electroencephalography revealed sharp-and-slow waves on left central regions. Visual and auditory evoked potentials were normal. Standard education was interrupted before the child started primary school, and she attended a school for special-needs children. On physical examination at 12 years old age, weight was 40kg (50^th percentiles), height was 1.55cm (25 percentiles), and head circumferences was 53cm (75^thpercentiles). There were no malformations at the physical examination. No dysmorphic features were noted. Abdominal sonogram, echocardiogram, skeletal X-rays were unremarkable. There was no problem during the neonatal period. She smiled at 12 weeks, sat at 10 months, crawled at 17 months and walked independently at 24 months. Language was delayed with first words at 3 years. Global developmental delay was noticed but general health was good. She was not fully toilet trained until the age of 9 years.Her intellectual quotient (IQ) was estimated at 60, indicating moderate intellectual disability on the Wechsler Intelligence Scale for Children Revised. Case 2:The proband’s mother (40 years old), had mild intellectual disability and schizophrenia. She is the second child of healthy, non-consanguineous parents and was born at 38 weeks via Caesarean section. Generally her physical examination was normal without any dysmorphic features or malformation. She had difficulties during her schooling, but did not attend a school for special needs. She was not able to achieve a high school curriculum, but followed a vocational course. She worked as a clerk in a grocery store and married at 24 years old. About 25 years old, she showed confused thinking, visual and auditory hallucinations. An assessment at 26 years of age confirmed a diagnosis of schizophrenia, and she has been taking risperidone and fluoxetine. Array CGH identified a 3.2 Mb terminal deletion at 12p13.33, which encompasses 27 genes (IQSEC3, SLC6A12, SLC6A13, KDM5A, CCDC77, B4GALNT3, NINJ2, WNK1, HSN2, RAD52, ERC1, LOC100292680, FBXL14, WNT5B, ADIPOR2, CACNA2D4, LRTM2, DCP1B, CACNA1C, FKBP4, ITFG2, NRIP2, FOXM1, C12orf32, TULP3, TEAD4, and TSPAN9). Twenty-seven OMIM listed genes are located in this region. Eight of them, SLC6A12, WNK1, HSN2, EPC1, CACNA2DA, CACNA1C, and TULP3 are known to have function in the central nervous system. Conclusions: The 12p13 deletion should be considered in any child with a differential diagnosis of epilepsy, ID and schizophrenia. Further study focusing on careful phenotyping across the lifespan to understand the potential contributions of genetic modifiers and environmental influence on the expressivity of 12p13 deletion and associated characteristics will be invaluable to further determine the impact that 12p13 deletion have on human psychopathology. Funding: None