A novel microdeletion/microduplication syndrome of 19p13.13

Purpose: Whole genome interrogation by array-based comparative genomic hybridization has led to a rapidly increasing number of discoveries of novel microdeletion and/or microduplication syndromes. We here describe the clinical and cytogenomic correlates of a novel microdeletion/microduplication of 19p13.13. Methods: Among patients referred to the Cytogenetics laboratory for array-based comparative genomic hybridization analysis, we identified four with a deletion and one with a duplication within 19p13.13. Confirmatory fluorescence in situ hybridization and parental studies were performed. Detailed clinical findings and array profiles were reviewed and compared. Results: Patients with deletions of 19p13.13 share a unique constellation of phenotypic abnormalities. In addition to developmental disabilities, the microdeletion manifested in overgrowth, macrocephaly, and ophthalmologic and gastrointestinal findings; in contrast, the single microduplication manifested in growth delay and microcephaly. Conclusion: The consistent constellation of clinical findings associated with copy number variation of this region warrants the designation of microdeletion/microduplication syndrome of 19p13.13. An approximately 311-340 Kb smallest region of overlap encompassing 16 genes was identified. Candidate genes include MAST1, NFIX, and CALR. Identification of this syndrome has led to recommendations for diagnostic work-up and follow-up of patients with this copy number variant. Integration of detailed clinical and array data is critical for advancing both patient care and human genomic research.