AB170. Loss of heterozygosity in child with multiple congenital anomaly

Background: Multiple congenital anomaly (MCA) has become an increasing problem in worldwide, since it significantly contributes to infant mortality rate (IMR) and caused many morbidities during neonatal until childhood period. Prevention has to be done to decrease the incidence through prenatal diagnosis, hence a proper postnatal definitive diagnosis should be established as a reference. Microaray system is one of the leading technique in order to detect copy number variations (CNV’s) and loss of heterozygosities (LOH’s) which may responsible to phenotype. This report is aimed to demonstrate a case of MCA with normal G-banding result, no pathologic CNV’s, with wide area of LOH’s contain several genes which may responsible to the phenotype.

Methods: Using Online Mendelian Inheritance in Man (OMIM) and Pictures of Standard Syndromes and Undiagnosed Malformation (POSSUM) databases, certain syndrome were tried to identify. Chromosome analysis were performed to detect large aberration. Microarray examination was done using Infinium CytoSNP-850K DNA analysis bead chip kit from Illumina. Chip was scanned using Hi-scan scanner from Illumina. Data were extracted using genome studio software. Data were analyzed using Nexus software.

Results: A 8-year-old girl was brought by parents to hospital with a chief complains dyspnea and looks cyanosis since 1 month prior to admission. She was born spontaneously, full term, no cyanosis, with distinctive face. Birth weight was 2,800 g. Her growth was retarded, but her development was normal. There is no history of seizure. Patient was a student in 3^rd grade of elementary school, with an average level of intelligence. Physical examination reveals tachypnea and cyanosis. There was pansystolic mur-mur without gallop. Clubbing fingers were noticed. There are several dysmorphic feature such as frontal bossing, wide frontal, depressed nasal bridge, hypertelorism, down slanting palpebrae, asymetric face (hemi hypoplasia), midfacial hypoplasia, strabismus. No chromosomal aberration was found. Microarray examination showed benign duplication regions at chromosome 21, 22 and 7. Benign deletion regions were found at chromosome 21 and 6. There are two large regions of heterozygosity (ROH) more than 5 Mb in size, which are located at chromosome 1 and 3. Those regions consist of 29 genes, which might responsible to the phenotype.

Conclusions: Unrecognized MCA with normal chromosome results needs further evaluation using microarray system. Although CNV’s calling give normal result, SNP calling might shows important finding. In this case microarray examinations showed 2 large regions of heterozygosity (ROH) consist of 29 genes which might responsible to the phenotype.

Keywords: Multiple congenital anomaly (MCA); definitive diagnosis; microarray; loss of heterozygosity