16p11.2 Recurrent Microdeletion

Clinical characteristics The 16p11.2 recurrent microdeletion phenotype is characterized by developmental delay, intellectual disability, and/or autism spectrum disorder (ASD). Developmental delays are related to diminished language, cognitive function, and motor impairments. While IQ scores range from mild intellectual disability to normal, those with IQ scores in the average range typically have other developmental issues such as language delay or ASD. Expressive language appears to be more affected than receptive language. Seizures are observed in approximately 20% of individuals with the recurrent microdeletion. Macrocephaly is common, usually becoming apparent by age two years. Chiari malformations/cerebellar ectopia are the most frequently observed structural brain abnormalities. In individuals with the 16p11.2 recurrent microdeletion the frequency of birth defects of all types is slightly increased, with vertebral anomalies appearing to be most frequent. Diagnosis/testing The 16p11.2 microdeletion is defined as the recurrent ~593-kb heterozygous deletion at the approximate position of 29.6-30.2 Mb in the reference genome (GRCh37/hg19). The microdeletion is identified by genomic testing that determines copy number of sequences, such as chromosomal microarray (CMA). This deletion cannot be detected by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques. While FISH analysis is not appropriate for identification of the deletion in a proband, it may be used to test relatives of a proband who is known to have the deletion. Management Treatment of manifestations: Treatment should be targeted to the specific deficits identified. Full developmental assessment, including neuropsychological testing by a clinical psychologist, is strongly suggested to establish neurodevelopmental needs and treatment recommendations. Refer to a neurologist if seizures are suspected. Because of the high risk of obesity beginning in adolescence, encourage healthy eating habits with attention to portion size and an active lifestyle from a young age. Routine management of vertebral anomalies. Surveillance: Routine surveillance, screening, and management based on American Academy of Pediatrics published guidelines on developmental delays and ASD. Maintain a low index of suspicion for possible seizures (which may manifest as, e.g., abnormal movements, staring spells). Obtain brain MRI if manifestations of Chiari I malformation appear. Periodic reevaluation by a medical geneticist to apprise the family of new developments and/or recommendations and facilitate long-term monitoring for emerging medical and/or mental health concerns. Genetic counseling 16p11.2 microdeletion is inherited in an autosomal dominant manner. The proband often has a de novo deletion; however, the deletion can also be transmitted from a parent to a child. Prenatal diagnosis for at-risk pregnancies requires prior identification of the deletion in an affected family member. Interpretation of results from prenatal testing is challenging given the inherent difficulty in accurately predicting the phenotype.