Purpose or Case Report: Xq21 deletions are rare and infrequently documented in the medical literature. Genomic analysis of deletions in Xq21 indicates an association with X-linked deafness (XLD), intellectual disability, and choroideremia. A limited number of studies have assessed the significance of cochlear malformations with brain parenchymal abnormalities. A possible mechanism linking inner ear deformity and hypothalamic malformations has been attributed to a DNA transcription factor, encoded by POU3F4, playing a role in nervous system, pituitary gland, hypothalamus, and inner ear development.

The subject of this case is a 14-month-old male with a history of bicuspid aortic valve and developmental delays that presented to otolaryngology with hearing loss. He failed his newborn hearing screening, and subsequent auditory brainstem response evaluation revealed bilateral mixed conductive and sensorineural hearing loss.

His magnetic resonance imaging (MRI) internal auditory canal (IAC) study at 13 months of age showed features consistent with congenital XLD with incomplete partition type 3 (IP-III) and associated bilateral symmetric structural abnormalities of the inner ear structures. Fluid-signal intensity was noted in the bilateral middle ear cavities with partial mastoid effusions. There was also evidence of hypothalamic malformation.

His genetic testing for chromosome microarray at 15 months of age showed a 12246 kb pathogenic deletion at Xq21.1q21.32 that was identified and confirmed in his mother as well. The deleted intervals involve 16 genes, three of which (POU3F4, ZNF711, CHM) are associated with known clinical disorders and were confirmed by a hearing loss gene panel. Pathogenic variants in the POU3F4 gene are associated with X-linked deafness-2 (DFNX2) and presentation of hearing loss. Pathogenic variants in CHM are associated with choroideremia, characterized by retinal pigment epithelium and photoreceptor degeneration. Pathogenic variants in ZNF711 are associated with intellectual disability.

The purpose of this case report is to comment on the clinical presentation and radiologic findings of an infant with Xq21 deletions to add to existing literature on XLD. Malformations in the hypothalamus associated with IP-III currently have unknown clinical significance, and IP-III anomaly may affect the selection of cochlear implant type.
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