Maternally Inherited Atypical 22q11.2 Microduplication Presenting with Unilateral Microtia and Aural Atresia: A Case Report of Evidence for an Association with Severe Ear Malformations.

Abstract

Introduction: 22q11.2 Microduplication syndrome is a genomic disorder characterized by extreme phenotypic variability and reduced penetrance. While minor ear anomalies are common, severe malformations like microtia and aural atresia are rarely reported. We present a unique case of maternally inherited 22q11.2 microduplication with severe external ear defects but superior neurodevelopment.

Case presentation: A male neonate was diagnosed with a 2.7-Mb atypical proximal 22q11.1-q11.21 duplication involving 0.7-Mb LCR22A-LCR22B region via chromosomal microarray analysis. Multiplex ligation-dependent probe amplification confirmed the duplication was inherited from his phenotypically normal mother. Clinical evaluation revealed Marx grade III microtia and complete aural atresia of the right ear, along with mild pulmonary stenosis. Despite these physical findings, the patient demonstrated exceptional cognitive outcomes, achieving a full-scale IQ of 135 and advanced language skills at 36 months.

Conclusion: This case described a rare and atypical inherited 22q11.2 microduplication and expands the phenotypic spectrum of the syndrome associated with this genomic disorder by associating it with severe primary ear malformations. The presence of dosage-sensitive genes like IL17RA, CECR2, and SLC25A18 likely drives these craniofacial anomalies and may help explain the phenotypic overlap with the Oculo-Auriculo-Vertebral Spectrum.