Distal 1q Duplication and Distal 9p Deletion: A Follow-Up Case Report and Literature Review on Candidate Genes for 9p Deletion Syndrome

Distal 1q duplication and distal 9p deletion are rare chromosomal aberrations associated with developmental delay and mild to moderate congenital malformations. There are inconsistent findings regarding the critical region for trigonocephaly within 9p deletion syndrome. A recent analysis of the largest 9p- cohort to date, however, delineated two critical regions and emphasized the need for replication. We report on a trigonocephalic child with a de novo 46.09 megabases (Mb) terminal duplication of 1q and a 5.31 Mb terminal deletion in 9p, described as 46,XX,der(9)t(1;9)(q32.1;p24.1). The clinical course was predominantly influenced by the 1q duplication. Trigonocephaly, however, was consistent with 9p deletion syndrome. Our findings support the delineation of [GRCh38] 9:3,418,241-5,341,746 as a critical region for trigonocephaly within 9p deletion syndrome. We propose that haploinsufficiency of RFX3, along with complex gene interactions, contributes to the mechanism for disease.