Mohd Fadly et al. Journal of Medical Case Reports 2012, 6:30 http://www.jmedicalcasereports.com/content/6/1/30 only [3]. However, due to the absence of a distinct clini- cal presentation and the limitation of routine chromoso- mal analysis techniques, definitive diagnosis in younger children is difficult. Conventional cytogenetic analysis of patients with syn- dromic features has largely reported findings of a nor- mal karyotype. This necessitates the adoption of a more sensitive method to detect the occurrence of any submi- croscopic chromosomal aberration. Microarray-based comparative genomic hybridization (array-CGH) is a high-throughput technique that offers rapid genome- wide analysis at high resolution. Array-CGH is designed to detect not only genome-wide chromosomal and seg- mental deoxyribonucleic acid (DNA) copy number changes, but also map and measure the regions of amplification, which may be associated with a wide range of diseases, from developmental disorders to can- cer. The use of current array-CGH technology enables the detection of submicroscopic chromosomal aberra- tions at multiple loci and localization of disease gene regions for subsequent candidate gene identification. Case presentation Our patient was a three-year-old Malaysian Chinese girl. She was the second of two children. Her parents were healthy and non-consanguineous. There was no signifi- cant family history. She was delivered at term via an elective lower segment Cesarean section with a birth weight of 2.63 kg. A pelvic cyst was detected during the antenatal period, but this had resolved spontaneously when a repeat ultrasound was done at six weeks of age. She was noted to have inspiratory stridor and a diagno- sis of laryngomalacia was made at 10 weeks of age. She showed a failure to thrive with slow feeding. Her growth parameters of weight, length and head circumference were below the third percentiles. She was given nasogas- tric feeding. A barium swallow showed no abnormalities. Her weight gradually improved when a percutaneous gastroenterostomy tube was inserted. A physical exami- nation at one year of age showed inspiratory stridor and dysmorphic features, such as a prominent nasal bridge, hypertelorism, down-slanting palpebral fissures, a small mouth, micrognathia, low set ears, sparse hair and bilat- eral broad thumbs and great toes (Figure 1). There was a soft systolic murmur heard on auscultation of the left sternal edge. She had generalized hypotonia but no other neurological deficits. She had mild to moderate global developmental delay, was only able to scribble, climb steps slowly and hold on to the rails, had no meaningful word in her speech but was able to obey simple commands and communicate with sign language. Investigations showed that she had a normal full blood count and metabolic studies, a normal karyotype and normal results for a DNA methylation study for Prader- Page 2 of 7 Willi syndrome. An echocardiogram showed a moderate size atrial septal defect. She had refractive errors and failed a distraction test. A peripheral blood sample was sent for array-CGH analysis at the age of one year and seven months. Cytogenetic analyses of our patient and her healthy parents were performed by G-banding techniques at 550 bands of resolution on metaphase chromosomes obtained by standard procedures from peripheral blood lymphocytes. Molecular karyotyping was performed using commercially available high resolution 244K 60- mer oligonucleotide microarray slide (Human Genome CGH Microarray 244A Kit, Agilent Technologies, Santa Clara, CA, USA) according to the manufacturer’s proto- col. This platform allows a genome-wide survey and molecular profiling of genomic aberrations with an aver- age resolution of about 10 kb. Cytogenetic analysis of our patient and her parents showed that they had normal karyotypes. Array-CGH analysis revealed a microdeletion of chromosome 16 involving band p13.3, with the first clone locating at 3, 651, 083 base pairs on proximal 16 p13.3 and the last clone locating at 3, 771, 464 base pairs on distal 16 p13.3, according to the University of California Santa Cruz Gen- ome Browser on Human March 2006 Assembly (NCBI36/hg18). The size of the deletion was estimated to be about 120 kb. The deletion was confirmed by a dye swap experiment of array-CGH. Multiplex ligation- dependent probe amplification (MLPA) experiments were performed to validate the array-CGH finding and to determine the parental origin of the deletion. The dele- tion was confirmed to be hemizygous and de novo using SALSA MLPA kit P313-A1 CREBBP (Microbiology Research Centre Holland, Amsterdam, The Netherlands). Discussion Chromosomal imbalances are known causes of genetic disorders and often result in a syndromic condition. We here describe a three-year-old girl with a global develop- mental delay, dysmorphic features and multiple congeni- tal anomalies, carrying a 120 kb microdeletion of chromosome 16 p13.3 detected by array-CGH (Figure 2). The deletion region encompasses two known genes, for tumor necrosis factor receptor-associated protein 1 (Trap1) and Crebbp. It has been demonstrated that the Trap1 gene is located on chromosome 16 p13.3 between 3, 648, 039 and 3, 707, 599 base pairs while the Crebbp gene is located on chromosome 16 p13.3 between 3, 716, 570 and 3, 870, 712 base pairs (NCBI36/hg18). The deleted region in our patient, identified by array-CGH, was located between 3, 651, 083 and 3, 771, 464 base pairs. Crebbp was partially deleted while its neighbor gene, Trap1, was deleted. Further study by MLPA tech- nique confirmed the deletion within the Crebbp gene to