Natasha Ferreira Santos da Cruz

Kabuki Syndrome (KS) is a rare multiple congenital anomaly syndrome originally described in 1981 by Japanese clinicians. KS belongs to the family of chromatinopathies, a group of disorders characterized by abnormalities in chromatin regulation due to germline mutations in the KMT2D or KDM6A genes. KS is characterized by five cardinal manifestations: (1) postnatal growth deficiency, (2) skeletal anomalies, (3) dermatoglyphic anomalies - including persistent fetal pads, (4) mild-to-moderate intellectual disability, and (5) typical facial features. Ocular abnormalities have been reported in more than one-third of patients with KS, but abnormalities involving the retina are rare. Currently, five accounts describing patients with KS and documented macular lesions exist within the literature. However, only two of these reports provide concurrent genetic confirmation. We describe the unique case of a female infant with molecularly confirmed KS due to a novel pathogenic variant in KMT2D who presented with retinopathy of prematurity (ROP) and bilateral macular lesions. Although our patient accounts for the sixth known case of foveal lesions associated with KS, she represents the third molecularly confirmed case of a de novo, nonsense KMT2D variant with macular abnormalities. In silico analysis with the prediction program MutationTaster found the mutation to be deleterious. Genetic testing, along with ophthalmologic examination and multimodal imaging, are indispensable tools for physicians, especially when confronted with patients suspected of having KS. When effectively used together, these tools can facilitate vision-preserving strategies.