AB016. Developing diagnostic strategy of multiple congenital anomalies in Indonesia

Background: Pediatricians quite often must deal with multiple congenital anomalies (MCA). Without a correct diagnosis, many available forms of therapy will be under-or-overused and counseling about prognosis and recurrence risk maybe unrealistic. The basis for diagnosis of MCA involves a combination of defining the physical manifestations and diagnostic genetic testing. Chromosome analysis is a standard practice to unravel the etiology of MCA. Conventional cytogenetic method has limitation in detecting abe1rrations less than 5 Mb in size. Microarray technology could overcome this obstacle. The aim of this study is to develop diagnosis strategy of MCA cases.

Methods: Seventy two MCA cases were recruited from July 2013 until June 2014. Fifty one subjects were diagnosed phenotypically using OMIM and POSSUM databases. Subsequently, chromosome analysis were performed as a first step of diagnosis strategy. Nine cases among those subjects found to have chromosome aberrations, whereas twelve cases showed normal karyotypes. Eight subjects from the normal karyotype group have a good quality of DNA and proceed to microarray examination. Microarray examination were done at Department of Medical Genetics, UMC Utrecht, Netherlands, using Infinium CytoSNP-850K DNA analysis bead chip kit from Illumina. Chips were scanned using Hi-scan scanner from Illumina. Data were extracted using genome studio software. Data were analyzed using Nexus software.

Results: Nine out of twenty cases were found to have chromosome aberrations. Those aberrations are:46,XY,add(13)(q34); 46,XY,6 Mar, 17 dmin; 46,XX,r(4)(p16q35); 46,XY,22ps+; 46,XY,add(5)(p15); 47,XX+G; 46,XX/45XX Rob (13,15/q10.2,q10), 45XX Rob (13,14)(q10,q10); 46,XX, ring 13; 45,XY,der(2)del(2)(q37.3)t(2;15)(q37.2;q11.2). Five out of eight subjects which tested by microarray showed normal array. Two subjects showed well known deletion syndrome, which are Wolf-Hirschhorn syndrome and Williams-Beuren syndrome. One case has normal array with two large regions Lost of Heterozygosity.

Conclusions: The first step of MCA’s diagnostic strategy is to do phenotype screening using the established databases. Subsequently patients grouped as “known” or “unknown” MCA. Second step is to perform chromosome analysis, either to confirm diagnosis or to find chromosome aberration. Unestablished diagnosis should be examined further using microarray.

Keywords: Multiple congenital anomalies (MCA); conventional chromosome analysis; microarray chromosome analysis