Craniofacial dysmorphism and developmental disorders among children with chromosomal microdeletions and duplications...

Microarray comparative genomic hybridization is an extremely sensitive technology that increasingly identifies deletions and duplications of unknown significance. Our objective was to determine whether children with autism and other developmental delays who have genomic imbalances manifest more craniofacial dysmorphism and have lower cognitive scores than children from the same clinic population who have normal microarrays.

A clinical geneticist, blinded to the history, reviewed photographs for craniofacial dysmorphism. Forty-five (24%) of 187 children who had a microarray had a deletion or duplication >200 kb. Thirty-six of those with abnormal microarrays (11 microdeletions and 25 duplications) had completed their evaluation, which included 3 deletions and 10 duplications of unknown significance. Subjects with and without microarray anomalies did not differ in age, sex, growth parameters, parental age or education level, insurance status, or cognitive scores.

Twenty-eight (78%) of the 36 children with microarray anomalies had craniofacial dysmorphism as compared with 45% of those with normal microarrays (p = .0005). Among the 13 children with microarray abnormalities of unknown significance, 10 (77%) were dysmorphic, similar to 18 (78%) of 23 who had a genomic imbalance known to affect development. Among the 10 children with dysmorphism and a microarray anomaly of unknown significance, 7 also had an IQ ≤70 and/or a diagnosis of autism.

Microdeletions and duplications not previously known to be associated with human disease were strongly associated with craniofacial dysmorphism, cognitive scores ≤70, and a diagnosis of autism in this clinic population, providing presumptive evidence that these genomic imbalances are clinically significant.