SSBP Information Sheet
Kabuki syndrome (KS) is a mental retardation-malformation syndrome affecting multiple organ systems with a broad spectrum of neuromuscular dysfunction and mental ability.

It was first reported independently by Niikawa et al. (1981) and Kuroki et al. (1981) at two Japanese centers. They each described 5 Japanese children with a characteristic array of multiple congenital anomalies and mental retardation. Since the first description by Niikawa and Kuroki worldwide over 300 cases are described. Dr. Niikawa and colleagues have written of at least 100 cases in Japan. Outside of Japan an increasing number of patients have been recognized.

Alternative names: Niikawa-Kuroki syndrome; Kabuki make up syndrome The resemblance of the characteristic peculiar faces seen in these patients to the make-up of the actors in the Japanese traditional Kabuki theater gave this syndrome its alternate name: Kabuki make-up syndrome. However in counseling parents the designation 'Kabuki syndrome' seems to be more appropriate than 'Kabuki make-up syndrome'.

Incidence / prevalence: Kabuki syndrome is rare genetic disorder. The prevalence is estimated to be 1/32.000, with a sex ratio of 1:1. Cases have now been reported across all ethnic groups.

Genetics /aetiology: The etiology is supposed to be heterogeneous and is unknown in the majority of cases. Some patients have (submicroscopical) cytogenetic abnormality (Huang and Milunski, 2003; Niikawa et al, 2004). An autosomal dominant mode of inheritance with a de novo mutation is assumed as well.

Physical phenotype: The syndrome (McKusick number 147920) is clinically variable and characterized by a diverse spectrum of 'symptoms'. Features of the syndrome include the typical face, postnatal growth retardation, skeletal anomalies, dermatoglyphic abnormalities and mild to moderate mental retardation. Other additional features are velopharyngeal incompetence, dental abnormalities, hypotonia, joint laxity, congenital heart defects, urogenital anomalies, seizures, a susceptibility to infections, visual and hearing anomalies. About 50% of the children acquire hearing loss due to frequent ear infections. This can contribute to delayed speech development. Some children are helped with hearing aids; others use a combination of hearing aids and other magnification units such as 'phonic ear'. A cleft palate may cause feeding problems and speech difficulties.

The facial phenotype is very characteristic at all ages and is already present in early infancy. The characteristic peculiar faces seen in these patients include long palpebral fissures, lower palpebral eversion, arched eyebrows, eversion of the lower lateral eyelids, long eyelash, epicanthus, depressed nasal tip, short nasal septum, large and prominent ears and micrognathia.
Typical are also the fingertip pads, brachydactyly and short 5th finger.

Psychological phenotype: Information about the cognitive and behavioral characteristics associated with Kabuki syndrome is still limited. Studies on clinical manifestation, including cognition demonstrate that in general patients are mildly to moderately mentally retarded (Curfs et al. 2000; Kawame et al. 1999;Mhanni et al. 1999; Ho & Eaves 1997; Galan-Gomez et al. 1995; Ilyina et al. 1995; Schrander et al. 1994; Niikawa et al. 1988; Wilson 1998).

But in some instances patients were found to function in the borderline to low average range of intelligence and profound range of intelligence. Small number of patients with severe mental retardation have been reported (Pebenito and Ferreti, 1989; Philip et al. 1992) and small number of patients with normal intelligence have been reported by Halal et al. 1989; Niikawa et al.1988; Philip et al. 1992. These patients though they may need assistance with speech and fine motor skills, are able to follow the regular curriculum in school.
Speech and language development is most often delayed and problematic. Poor morphosyntactic development is a common feature. Lexical and phonological problems seem to be less typical (Defloor et al. 2004).

Guidelines for preventive management: Based on clinical experience in groups of patients guidelines have been proposed (Wilson, 1998; Schrander-Stumpel et al, 2004).

Parent association: Kabuki syndrome networks exist in different countries to act both as a source and index of information on Kabuki syndrome and to help families support each other by sharing their experiences. The Canada / USA Kabuki syndrome Network and European Kabuki syndrome Network publish together the Kabuki Journal

References:
Kuroki, Y., Susuki, Y., Chyo, H., Hata, A., Matsui, I. (1981) A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation . J. Pediatr 99: 570-573

Miyake N, Harada N, Shimokawa O, Ohashi H, Kurosawa K, Matsumoto T, Fukushima Y, Nagai, T., Shotelersuk V, Yoshiura K, Ohta T, Kishino T, Niikawa N, Matsumoto N. On the reported 8p22-p23.1 duplication in Kabuki make-up syndrome (KMS) and its absence in patients with typical KMS. Am J Med Genet. 2004, Jul 15; 128A(2):170-172

Milunsky JM, Huang XL. (2003). Unmasking Kabuki syndrome: chromosome 8p22-8p23.1 duplication revealed by comparative genomic hybridization and BAC-FISH. Clin Genet 64: 509-516

Niikawa, N., Matsuura, N., Fukushima, Y., Ohsawa, T, Kajii, T. (1981) Kabuki make-up syndrome: A syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J. Pediatr 99:565-569

Schrander-Stumpel C, Meinecke P, Wilson G, Gillessen-Kaesbach G, Tinschert S, König R, Philip N, Rizzo R, Schrander J, Pfeiffer L, Maat-Kievit A, Burgt I vander, Essen T van, Latta E, Hillig U, Verloes A, Journel H, Fryns JP. (1994) The Kabuki (Niikawa-Kuroki) syndrome: further delineation of the phenotype in 29 non-Japanese patients (1994) Eur J Pediatr 153: 438-455

Schrander-Stumpel CTRM, Schrander JJP, van de Ven H, Van der Vlugt H, Defloor T. Curfs LMG (2004) Kabuki syndrome: clinical features in 20 patients, review of the literature and guidelines for preventive management. Am J Med Gen in press

Defloor T, Van Borsel J, Schrander-Stumpel CTRM, Curfs LMG (2004). Expressive language in children with Kabuki syndrome. Am J Med Gen in press

Wessels MW, Brook AS, Hoogeboom J, Niermeijer MF, Willems PJ (2002). Kabuki syndrome: a review study of three hundred patients. Clin Dysmorphol 11: 95-102

Wilson, G.N. (1998) Thirteen cases of Niikawa-Kuroki syndrome: report and review with emphasis on medical complications and preventive management. American Journal of Medical Genetics 79: 112-120

Kaame, H., Hannibal, M.C., Hudgins, L., Pagon, R.(1999) Phenotypic spectrum and management issues in Kabuki syndrome. J. Pediatr 134, 4, 480-485

LMG Curfs and CTRM Schrander-Stumpel, September 2004

e-mail:
Ros_anderson@msn.com - The Kabuki Syndrome Support Group