Abstract
Solitary median maxillary central incisor (SMMCI) syndrome, the mildest form of the holoprosencephaly spectrum, is a rare anomaly characterized by the presence of a single midline central incisor in both the deciduous and permanent dentitions. Affected individuals can present with additional midline defects beyond dental findings. The 22q11.2 deletion syndrome (22q11.2 DS) arises from heterozygous microdeletions on chromosome 22q11.2, with breakpoints frequently located in eight clusters of low-copy repeats (LCR22A-H). Herein, we report an atypical case of 22q11.2 microdeletion in a male patient with SMMCI and additional features including hypothyroidism, ventricular septal defect, and several facial anomalies. The telomeric breakpoint was located in a segmental duplication 0.5 Mb distal to LCR22D, whereas the centromeric breakpoint was within LCR22C. Both segmental duplications shared a high level of sequence identity (97.2%), indicating the possibility of non-allelic homologous recombination (NAHR). This report supports the critical role of NAHR in the formation of rearrangements between regions other than LCR blocks and establishes a clinical association between 22q11.2 microdeletion and SMMCI.