17q12 Recurrent Duplication

Clinical characteristics In individuals with clinical manifestations the 17q12 recurrent duplication is characterized by intellectual abilities ranging from normal to severe disability and other variable clinical manifestations. Speech delay is common, and most affected individuals have some degree of gross motor delay. Seizures are present in 75%. Up to one third have eye or vision problems; cardiac and renal anomalies occur in rare cases. Other neurodevelopmental and psychiatric conditions reported in a subset of affected individuals are autism spectrum disorder, schizophrenia, and behavioral abnormalities (aggression and self-injury). The 17q12 recurrent duplication likely has reduced penetrance and variable expressivity since it is inherited in most instances from a parent who is often minimally affected or phenotypically normal. Diagnosis/testing The 17q12 recurrent duplication is diagnosed by detection of a 1.4-Mb submicroscopic heterozygous duplication at the approximate position of chr17:34,815,072-36,192,492 Mb [GRCh37/hg19] in the reference genome. Individuals found to have this rare duplication were typically referred for testing because of intellectual disability and/or developmental delays, and occasionally because of multiple congenital anomalies. Management Treatment of manifestations: Treatment should be tailored to the specific needs of the individual. Those with developmental delays, cognitive disability, and/or behavioral problems should be evaluated by a neurodevelopmental pediatrician or clinical psychologist/psychiatrist. Seizures should be managed by a neurologist using standard practice. Individuals with cardiac or renal abnormalities should be managed by the appropriate specialist. Surveillance: Regular assessment of psychomotor development is recommended for all children with the 17q12 recurrent duplication as well as psychological evaluation in both affected children and adults. Evaluation of relatives at risk: Presymptomatic diagnosis and treatment is warranted in at-risk relatives to identify as early as possible those who would benefit from close assessment/monitoring of developmental milestones in childhood or psychological assessment/intervention through adulthood. Genetic counseling The 17q12 recurrent duplication is inherited in an autosomal dominant manner, with approximately 10% of duplications occurring de novo and approximately 90% inherited from a parent who is often minimally affected or phenotypically normal. Prenatal diagnosis for at-risk pregnancies requires prior identification of the duplication in an affected family member. Interpretation of results from prenatal testing is challenging given the inherent difficulty in accurately predicting the phenotype.