16p11: Description of the behavioral and morphological phenotype of a “mirror” syndrome

Abstract

Objective: Copy number variations (CNVs) in the 16p11.2 gene region are translated into different morphological and neurobehavioral phenotypes. The main objective of our study is to describe these differences according to the type of CNV. It is proposed as a secondary objective the design of a protocol of assessment and follow-up for these patients. Methods: Retrospective descriptive study in patients with CNVs in 16p11.2 diagnosed in a Tertiary Hospital using Array-CGH. We collected anthropometric data, dysmorphic features, and performed neuropsychological assessments (ASD, ADHD, intellectual and neurodevelopment screening). Results: A total of 9 patients with 16p11 CNVs were studied. 6 cases with a deletion, being 100% of these de novo; and 3 cases with a duplication, being 67% of the cases inherited. Patients with deletions were overweight / obese and macrocephalus, while patients with duplications present a normal BMI and microcephaly. Clinical manifestations observed in the patients studied included ophthalmological disorders (22%), psychomotor retardation (67%), mild intellectual deficit (56%), autism spectrum disorder (22%) and ADHD (78%). All of the patients that exceed cut point in SNAP -IV in the sample were carriers of a deletion, predominating in them the inattentive subtype ADHD. Conclusion: CNV carriers in the 16p11.2 gene region present mirror anthropometric phenotypes and the most frequently associated conditions were psychomotor development delay, ASD, and ADHD. Inattentive type ADHD is the most commonly observed in patients with deletions, and no significant differences in neuropsychological profile were observed at other levels depending on the type of CNVs. Taking into account the above, it is proposed to carry out an assessment and follow-up protocol that includes a standardized medical history, a comprehensive physical examination including ophthalmologic examination and complementary examinations to rule out intellectual deficit, ASD and ADHD.