BACKGROUND: Since the establishment of chromosomal microarrays in clinical practice, many new microdeletion/microduplication syndromes have been identified, including 18q11.2 microdeletion. Chromosome 18q deletion syndrome is commonly classified into distal deletion and a much rarer proximal interstitial deletion spanning the 18q11.2-q21.1 region.
METHODS: We report two new patients and review 27 additional cases in DECIPHER/ClinGen databases and four cases from the literature, with more proximal 18q deletions involving 18q11-q12 (band 1 only; 17.2-43.5 Mb position) deletion.
RESULTS: Common presentations of 18q11-q12 deletions include developmental delay/intellectual disability (DD/ID) (82%); speech delay/autism/attention deficit and hyperactivity/other behavioral problems (30%); conotruncal heart defects (15%); and subtle/non-specific facial dysmorphism. The deletion in four out of five cases with cardiac defect was distal to GATA6, suggesting an alternative mechanism other than haploinsufficiency of GATA6 as an underlying cause of cardiac malformations. Precocious puberty with advanced skeletal age was first observed in one patient, suggesting a unique and expanded phenotype of proximal 18q deletion. When comparing genotype-phenotype correlations from the present study with previous reports, the critical regions for selected phenotypes of 18q11-q12 deletion syndrome could be narrowed down as follows: 38.8-43.5 Mb for moderate to severe DD/ID, 19.6-24.4 Mb and 26.9-28.6 Mb for conotruncal heart defect.
CONCLUSION: The detailed clinical delineation of the proximal 18q deletions identified in this study should contribute to better understanding of the genotype-phenotype correlations and better long-term care of patients with this rare syndrome.