The Use of Array CGH in a Cohort of Albanian Children with Development Delay/Intellectual Disability, Congenital Anomalies and Dysmorphic Features

Background: The aim of our study was to identify chromosomal imbalances by microarray comparative genomic hybridization (array CGH) in DNA samples of children with developmental delay/intellectual disability, congenital anomalies and dysmorphic features, in which karyotype results cannot be obtained. This increased resolution of microarray technology over conventional cytogenetic analysis allows for identification of chromosomal imbalances primarily because of its higher sensitivity for submicroscopic deletions and duplications.

Objective: To present the first Albanian experience of an array CGH application. The cohort included 13 children with with developmental delay/intellectual disability, congenital anomalies and dysmorphic features. The patients were newborns and children with congenital anomalies diagnosed for the time period 2014-2016.

Methods. The cytogenetic analysis determined by a standard method of G-banding was performed for all our patients, while array CGH was performed on genomic DNA isolated from the blood of 11 cases. For all patients, karyotype analysis has been extended to parental samples.

Results: Among the 13 patients for one male patient, standard G-banding revealed 46,XY,dup(10)(q22) karyotype and for another male patient revealed 46,XY,del (7) (q21q22.2) karyotype. Among 11 patients that resulted with normal karyotype, array CGH revealed 4 patients (36,3 %) resulted with a duplication and a deletion, 2 patients (18 %) with a microdeletion, 2 patients (18%) with a duplication, 2 patients (18%) with a deletion and 1 patient (9%) with two deletions. In 3 out of the 11 patients the chromosomal aberration had been inherited from one of the healthy parents, carrier of balanced reciprocal translocation.

Conclusion: Array-CGH has improved significantly the genetic diagnosis of pediatric patients with developmental delay/intellectual disability, congenital anomalies and dysmorphic features.

The identification of the specific genetic defect in these patients clarify the diagnosis, suggest the prognosis and elucidate the risk of a disease in family members and future children.

• Keywords: congenital anomalies, deletion, duplication, intellectual disability, karyotype, microarray comparative genomic hybridization.