Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Alexandru Caramizaru
Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
Anca-Lelia Riza
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Simona Șerban-Sosoi
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Andrei Pîrvu
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Monica-Laura Cara
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Mihai-Gabriel Cucu
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Amelia Mihaela Dobrescu
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Ro-NMCA-ID Group
The Ro-NMCA-ID (RoNetwork Multiple Congenital Abnormalities with ID) Member of European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA) [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], 400011 Timisoara, Romania
CExBR Pediatric Neurology Obregia Group
Pediatric Neurology Rare Disease Expertise Center Obregia, Sos. Berceni nr. 10, Sector 4, 041914 Bucuresti, Romania
CExBR Pediatric Neurology “V. Gomoiu” Hospital Group
Center for Expertise in Rare Diseases in Pediatric Neurology, Pediatric Neurology Clinical Department, Children’s Clinical Hospital “Dr. Victor Gomoiu”, 022102 Bucharest, Romania
Elena-Silvia Shelby
National University Center for Children’s Neurorehabilitation “Dr. Nicolae Robănescu”, 44 Dumitru Mincă Street, District 4, 041408 Bucharest, Romania
Adriana Albeanu
Department of Pediatric Neurology, Clinical Emergency Children Hospital Brasov, Nicopole Street No. 45, 500063 Brasov, Romania
Florin Burada
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
Mihai Ioana
Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
The investigation of unexplained global developmental delay (GDD)/intellectual disability (ID) is challenging. In low resource settings, patients may not follow a standardized diagnostic process that makes use of the benefits of advanced technologies. Our study aims to explore the contribution of chromosome microarray analysis (CMA) in identifying the genetic etiology of GDD/ID. A total of 371 Romanian patients with syndromic or non-syndromic GDD/ID, without epilepsy, were routinely evaluated in tertiary clinics. A total of 234 males (63.07%) and 137 (36.93%) females, with ages ranging from 6 months to 40 years (median age of 5.5 years), were referred for genetic diagnosis between 2015 and 2022; testing options included CMA and/or karyotyping. Agilent Technologies and Oxford Gene Technology CMA workflows were used. Pathogenic/likely pathogenic copy number variations (pCNVs) were identified in 79 patients (21.29%). Diagnosis yield was comparable between mild ID (17.05%, 22/129) and moderate/severe ID 23.55% (57/242). Higher rates were found in cases where facial dysmorphism (22.97%, 71/309), autism spectrum disorder (ASD) (19.11%, 26/136) and finger anomalies (20%, 27/96) were associated with GDD/ID. GDD/ID plus multiple congenital anomalies (MCA) account for the highest detection rates at 27.42% (17/62). pCNVs represent a significant proportion of the genetic causes of GDD/ID. Our study confirms the utility of CMA in assessing GDD/ID with an uncertain etiology, especially in patients with associated comorbidities.
