Clinical characteristics: 16p12.2 recurrent deletion is characterized by variable clinical findings that do not constitute a recognizable syndrome. Of note, the significant bias in ascertainment of individuals undergoing clinical chromosomal microarray analysis (i.e., children with intellectual disability and developmental delay; individuals with schizophrenia) makes it difficult to accurately associate specific phenotypes with the 16p12.2 recurrent deletion. Findings commonly observed in children (probands) with this deletion include: developmental delay, cognitive impairment (ranging from mild to profound), growth impairment (including short stature), cardiac malformations, epilepsy, and psychiatric and/or behavioral issues. Other findings can include: hearing loss, dental abnormalities, renal and genital anomalies (the latter in males), and cleft palate ± cleft lip.
Diagnosis/testing: The diagnosis of 16p12.2 recurrent deletion is established by identification of a 520-kb heterozygous deletion on chromosome 16p12.2 on chromosomal microarray analysis or other genomic analyses.
Management: Treatment of manifestations: Treatment is directed to specific problems identified and may include developmental therapies; routine treatment of cardiac malformations, epilepsy, psychiatric and behavioral issues, hearing loss, and other malformations (e.g., orofacial clefting; renal, genitourinary, and dental anomalies).
Surveillance: Periodic: developmental evaluations; monitoring of cardiac, renal, urologic, and/or dental abnormalities, as needed; reevaluation by a clinical geneticist.
Evaluation of relatives at risk: Older and younger sibs of a proband should be tested for a 16p12.2 recurrent deletion to allow for close assessment/monitoring of developmental milestones and monitoring for neuropsychiatric manifestations in children with the deletion.
Genetic counseling: The 16p12.2 recurrent deletion is inherited in an autosomal dominant manner. The majority (~95%) of individuals with this recurrent deletion inherited the deletion from a parent (who may or may not have clinical features related to the recurrent deletion). If a parent is heterozygous for the 16p12.2 recurrent deletion, the risk that the sibs of a proband would inherit the deletion is 50%; however, the risk that sibs would be affected is less than 50% because of reduced penetrance for the deletion. Children with a family history of neurodevelopmental and psychiatric disease are more likely to present with severe clinical features of the deletion. If a 16p12.2 recurrent deletion has been identified in a family member, prenatal testing for pregnancies at increased risk is possible; however, it is not possible to reliably predict phenotype based on the laboratory finding of a 16p12.2 recurrent deletion.
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