Chromosomal Anomalies in a Portuguese “Idiopathic” Autism Sample

Background: Autism is a complex neurodevelopmental and a predominately genetic disorder defined by impaired reciprocal social interaction, communication and restricted, repetitive and stereotyped behavior. Approximately 2%-5% of individuals with autism spectrum disorder (ASD) have some form of chromosomal abnormality. The most common location is the chromosome 15q11-q13 region.

Objectives: This study aims to assess the chromosomal abnormalities found in a large sample of Portuguese children with idiopathic autism, observed over several years at our Unit.

Methods: Assessment of ASD entailed extensive interaction with patients in a clinical setting, the majority of who return frequently for follow up. ASD was diagnosed using ADI-R, CARS and DSM-IV-TR criteria. A comprehensive clinical history was collected, including the pre and per natal periods. We excluded the non-idiopathic ASD patients (Rett, Fragile X, neurocutaneous syndromes, endocrine, metabolic, trisomy 21 and other genetic disorders). High-resolution cytogenetic analyses were performed using peripheral blood lymphocyte cultures by standard protocols. Molecular cytogenetic was performed using paint and subtelomerics probes to clarified rearrangements.

Results: Of the 634 ASD patients with a male to female ratio of 4:1, 526 subjects were considered idiopathic (83%). They all had ADI-R positive and a 35 median CARS result. The median for Global Developmental Quotient (GDQ) was 62 and for Global Intellectual Quotient was 78. Within these group, nineteen subjects (3,6%), with ADOS positive and a 36 median CARS result (P₅ =30; P₉₅=52), presented chromosomal abnormalities. The median for GDQ was 44 and for Vineland Adaptive Behavior composite was 32 months (median chronological age=108 months). The chromosomal abnormalities were most frequently located on ch15q11-13 (FISH analysis) – 6 patients. Two siblings presented 46,XX del(5)(p15.2p15.2). The other chromosomal abnormalities were: two on 46,XY del(9)(pter); one each on 47,XY+r.ishr(15); 46,XYdel(1)(q); 46,XY rec(7)dup(7)ins(7)(q21.2p15.1p13)/mat; 46,XYdel(8)(p23.3); 46,XYdup(5)(pter); 46, XXinv(9)(q12q34.1); 46,XYinv(6)(q21q23.1); mos 47,XYY(26)/45,X(4); mos 46, XY,add(12)(p13.3)/46,XY.
 
Conclusions: Our findings corroborate other researches for overall prevalence of chromosomal abnormalities. Cytogenetic studies, that may guide molecular studies by pointing to relevant inherited or de novo chromosomal abnormalities, are a significant and worth doing initial approach for all idiopathic ASD. Finding chromosomal abnormalities may in fact provide a valuable contribution for genetic counseling of families and also to the identification of candidate gene regions for the disease.