Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 262; no. 6; pp. 1737 - 1744
• Main Authors: Vaclavik, Veronika, Navarro, Aurelie, Jacot-Guillarmod, Alain, Bottani, Armand, Sun, Young Joo, Franco, Joel A., Mahajan, Vinit B., Smirnov, Vasily, Bouvet-Drumare, Isabelle
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2024; Springer Nature B.V
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Acuity; Adolescent; Adult; Congenital defects; DNA - genetics; DNA Mutational Analysis; DNA-Binding Proteins - genetics; Dystrophy; Electroretinography; Exome Sequencing; Eye; Face - abnormalities; Female; Fluorescein Angiography - methods; Follow-Up Studies; Fundus Oculi; Hematologic Diseases - diagnosis; Hematologic Diseases - genetics; Hematologic Diseases - physiopathology; Humans; Macula Lutea - pathology; Macular Degeneration - diagnosis; Macular Degeneration - genetics; Macular Degeneration - physiopathology; Male; Medicine; Medicine & Public Health; Multimodal Imaging; Neck; Neoplasm Proteins - genetics; Ophthalmology; Pathogenicity; Patients; Phenotype; Phenotypes; Photoreceptors; Retina; Retinal Disorders; Time Factors; Tomography, Optical Coherence - methods; Vestibular Diseases - diagnosis; Vestibular Diseases - genetics; Vestibular Diseases - physiopathology; Visual Acuity; Macula; gene; Kabuki syndrome; Multimodal imaging; Adaptive optics; Dystrophy; Retinal imaging; Autofluorescence imaging; KMTD2 gene
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-023-06345-1

Background Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo nonsense variants in KMT2D , one novel. A follow-up of 10 years is reported. Pathogenicity of both de novo nonsense variants is analyzed. Methods Four eyes of two young patients were studied by full clinical examination, kinetic perimetry, short wavelength autofluorescence, full field (ff) ERGs, and spectral-domain optical coherence tomography (SD-OCT). One patient had adaptive optic (AO) imaging. Whole exome sequencing was performed in both patients. Results Both patients had de novo nonsense variants in KMTD2 . One patient had c.14843C>G; p. (Ser4948ter) novel variant and the second c.11119C>T; p. (Arg3707ter). Both had a stable Snellen visual acuity of 0.2–0.3. The retinal multimodal imaging demonstrated abnormalities at the fovea in both eyes: hyperreflectivity to blue light and a well-delimited gap—disruption of ellipsoid and interdigitation layer on OCT. The dark area on AO imaging is presumed to be absent for, or with structural change to photoreceptors. The ff ERGs and kinetic visual fields were normal. The foveal findings remained stable over several years. Conclusion Kabuki syndrome–related maculopathy is a distinct loss of photoreceptors at the fovea as shown by multimodal imaging including, for the first time, AO imaging. This report adds to the literature of only one case with maculopathy with two additional macular dystrophies in patients with Kabuki syndrome. Although underestimated, these cases further raise awareness of the potential impact of retinal manifestations of Kabuki syndrome not only among ophthalmologists but also other healthcare professionals involved in the care of patients with this multisystem disorder.