From Frimley Park Hospital (DL, MFPG), Surrey; and Great Ormond Street Hospital (DAT, ATM), London, United Kingdom.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Dan Lindfield, MRCOphth, Ophthalmology Department, Frimley Park Hospital, Portsmouth Road, Surrey, GU16 7UJ, United Kingdom. E-mail: firstname.lastname@example.org
Kabuki make-up (Niikawa–Kuroki) is a rare syndrome affecting 1 in 32,000 live births in Japan but is rarely seen in the rest of the world.1 Inheritance is predominantly sporadic and is thought to be due to new dominant mutations, thus rendering traditional gene linkage analyses difficult. However, recent work using exome sequencing has found the MLL2 gene to have a causative role in more than half of cases.2 The syndrome is characterized by mental retardation, short stature, and a typical facial appearance that includes everted lateral third of the lower eyelid, long palpebral apertures, arched eyebrows, broad nasal tip, prominent ear lobes, cleft or high-arched palate, conical teeth, missing permanent lower incisors, “screwdriver” upper incisors, and craniosynostosis.3,4 Many ocular manifestations have been reported but specific retinal features are uncommon.3–7 Ocular features include amblyopia, refractive errors, strabismus, nystagmus, colobomas, microcornea, corneal opacities, blue sclera, cataract, nasolacrimal duct obstruction, caruncular lipoma, macular deposits, retinal telangiectasia, and prepapillary gliosis.
A 9-month-old girl of non-Japanese heritage presented with failure to thrive and gynecomastia. A diagnosis of Kabuki syndrome was made by a multidisciplinary team based on characteristic facial features (Fig. 1), growth and developmental assessment, and radiological evidence in keeping with Kabuki syndrome (short 5th terminal phalanges). Molecular genetic testing for Kabuki syndrome was not available at the time.
Figure 1. Facial features of patient at 14 years old: everted lateral third of the lower eyelid, long palpebral fissures, arched eyebrows, and broad nasal tip.
At age 8 years, she presented with a convergent squint. Visual acuities were 6/24 in the right eye and 6/36 in the left eye; there was no significant refractive error. Both maculae exhibited hypopigmentation and hyperpigmentation (Fig. 2).
Figure 2. Fundus photographs: central depigmentation with surrounding densely pigmented region.
Electrodiagnostic testing revealed a normal full-field electroretinogram (Fig. 3). The pattern electroretinograms were normal, with well-defined p50 and n95 components (Fig. 4). Pattern reversal visual evoked potentials were elicited to a range of check sizes, but waveforms were broad and became attenuated to the smaller check sizes (Fig. 5). The electrophysiological assessment suggested bilateral macular dysfunction. Fourier optical coherence tomography showed subtle irregularity at the inner–outer segment junction of the fovea. This is shown with comparison infrared and autofluorescence images for the right eye (Fig. 6). There was no family history of any retinal or macular dystrophy and she had never been exposed to chloroquines.
Figure 3. Generalized retinal function measured by full-field flash electroretinograms fell within normal limits, at the 5th centile. Right eye electroretinograms are shown for a series of flash strengths presented photopically and scotopically. Waveforms show expected changes in amplitudes of a- and b-waves and time to peaks.
Figure 4. Pattern electroretinograms elicited to 50’ checks presented in 30° and 14° fields show normal p50 and n95 components, indicating normal macular retinal function within these regions.
Figure 5. Pattern reversal visual evoked potentials elicited with both eyes regarding a range of check sizes. The patient’s visual evoked potentials to the smaller checks are attenuated, indicating macular pathway dysfunction.
Figure 6. Fourier optical coherence tomography of the right eye with corresponding infrared and autofluorescence images. Optical coherence tomography illustrates subtle irregularity of the inner–outer segment junction.
Only three case reports document fundal features in patients with Kabuki syndrome. A single patient with Coats-type telangiectatic retinopathy5 and discrete yellow macular deposits without electrodiagnostic abnormalities have been reported in a 6-year-old boy.6 More recently, a 21 year old with confirmed Kabuki syndrome was referred with pre-papillary gliosis and tortuous retinal vessels and irregular foveal pigmentation.7
Electrodiagnostically confirmed maculopathy has not previously been reported in Kabuki syndrome. There is a possibility that it may be unrelated and coincidental, but Kabuki syndrome is poorly understood and recent reports suggest other possible new fundal features of this syndrome. Thorough ocular evaluation remains advisable in all cases of Kabuki syndrome.
- Ohdo S, Madokoro H, Sonoda T, Nishiguchi T, Kawaguchi K, Hayakawa K. Kabuki make-up syndrome (Niikawa-Kuroki syndrome) associated with congenital heart disease. J Med Genet. 1985;22:126–127. doi:10.1136/jmg.22.2.126 [CrossRef]
- Ng SB, Bigham AW, Buckingham KJ, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet. 2010;42:790–793. doi:10.1038/ng.646 [CrossRef]
- Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, skeletal anomalies associated with post-natal dwarfism and mental retardation. J Pediatr. 1981;99:570–573. doi:10.1016/S0022-3476(81)80256-9 [CrossRef]
- Niikawa N, Matsura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears and post-natal growth deficiency. J Pediatr. 1981;99:565–569. doi:10.1016/S0022-3476(81)80255-7 [CrossRef]
- Anandan M, Porter NJ, Nemeth AH, Blair E, Downes SM. Coats-type retinal telangiectasia in case of Kabuki make-up syndrome (Niikawa-Kuroki syndrome). Ophthalmic Genet. 2005;26:181–183. doi:10.1080/13816810500374433 [CrossRef]
- Elsherbiny SM. Macular deposits: a new feature of Kabuki syndrome?J Pediatr Ophthalmol Strabismus. 2002;39:251–253.
- Chuah JL, Chuah JK, Brown R. New fundus findings in a case of Kabuki syndrome. Eye. 2009;23:1483–1485. doi:10.1038/eye.2008.227 [CrossRef]