Kabuki syndrome is a congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids (reminiscent of the make-up of actors ... Kabuki syndrome is a congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids (reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form), a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy (Niikawa et al., 1981). For a discussion of genetic heterogeneity of Kabuki syndrome, see KABUK1 (147920).
Lederer et al. (2012) studied 2 girls and a boy with Kabuki syndrome. The 2-year-old boy and 13-year-old girl had a typical Kabuki syndrome phenotype, including long palpebral fissures, lateral eversion of the lower eyelid, and moderate to ... Lederer et al. (2012) studied 2 girls and a boy with Kabuki syndrome. The 2-year-old boy and 13-year-old girl had a typical Kabuki syndrome phenotype, including long palpebral fissures, lateral eversion of the lower eyelid, and moderate to severe intellectual disability; they also displayed long halluces. The facial features of the 10-year-old girl were not as classic, but she displayed many characteristics of the disorder, including lateral sparseness of the eyebrows, long eyelashes, strabismus, long palpebral fissures, large and prominent ears, persistent fetal fingertip pads, aortic coarctation, areolar fullness in infancy, and hirsutism; she also had mild developmental delay.
By array CGH analysis in 2 unrelated Belgian girls with Kabuki syndrome who were negative for mutation in the MLL2 gene (602113), Lederer et al. (2012) identified de novo Xp11.3 microdeletions, both of which contained part or all ... By array CGH analysis in 2 unrelated Belgian girls with Kabuki syndrome who were negative for mutation in the MLL2 gene (602113), Lederer et al. (2012) identified de novo Xp11.3 microdeletions, both of which contained part or all of the KDM6A gene (300128). In the 13-year-old girl, the deletion included KDM6A exons 21 through 29 and CXORF36, whereas in the 10-year-old girl, the deletion completely removed KDM6A, CXORF36, DUSP21 (300678) and FUNDC1 (300871). Sequencing of the KDM6A gene and targeted array CGH in a cohort of 22 MLL2-negative Kabuki syndrome patients revealed a de novo intragenic deletion in a 2-year-old Italian boy (300128.0001). Miyake et al. (2013) analyzed the KDM6A gene in 32 patients with Kabuki syndrome who were negative for mutation in the MLL2 gene and identified nonsense mutations in 2 male patients and a 3-bp deletion in a female patient (300128.0002-300128.0004). The 3 mutation-positive patients all had severe developmental delay and intellectual disability, but the female patient had fewer dysmorphic features than the male patients, who displayed a more severe phenotype with multiple organ involvement. Peripheral leukocyte genomic DNA from the female patient showed a random pattern of X inactivation, in a 57:43 ratio. Miyake et al. (2013) suggested that the mutation type as well as X-inactivation pattern in affected organs in females may determine the severity of Kabuki syndrome. Miyake et al. (2013) screened 81 patients with Kabuki syndrome for mutations in the MLL2 and KDM6A genes and identified KDM6A mutations in 5 (6.2%) and MLL2 mutations in 50 (60.7%). Of the 5 KDM6A mutations, including 2 that were novel, 4 were protein-truncating and 1 was an in-frame deletion in the Jumonji C domain. High-arched eyebrows, short fifth fingers, and infantile hypotonia were less commonly seen in patients with KDM6A mutations than in those with MLL2 mutations. All of the patients with KDM6A mutations had short stature and postnatal growth retardation, compared with only half of the patients with MLL2 mutations. Among the 2 female patients with KDM6A mutations, one with an in-frame deletion (300128.0004) had a random X-inactivation pattern, whereas the other with a frameshift mutation (300128.0005) showed marked skewing.