Oral features in Kabuki make-up

Syndrome
G. SPANO, G. CAMPUS, A. BORTONE, V. LAI, P.F. LUGLIÈ

ABSTRACT. Aim Kabuki make-up Syndrome is so named because of the characteristic facies of the affected patient.
The face is similar to a Kabuki actor’s mask. The main aim of this report was to describe the oral features in
Kabuki Syndrome, focusing on the tooth anomalies. Patients and methods Five subjects with Kabuki Syndrome,
identified by the Child Neuropsychiatric Clinic of the University of Sassari, Italy, were enrolled. Their medical
records were reviewed and oral and dental examinations were completed. The diagnosis was based upon the
typical pattern of malformations and dysmorphic features reviewed by Matsumoto and Niikawa. Results All
patients showed typical characteristics of the Syndrome such as a long palpebral fissure, lower palpebral
eversion, arched eyebrows, short nasal septum, prominent and large ears, fingertip pads, mental retardation, and
paramedian elevation of the lower lip. Conclusion Kabuki make-up Syndrome is of unknown origin but a genetic
aetiopathogenesis has been proposed. It is extremely rare; in Japan, where it is most frequent, it affects 1:32000
newborns. The typical facies of the syndrome, combined with general medical and dental examinations, are very
important for diagnosis confirmation.

KEYWORDS: Kabuki make up Syndrome; Oral features; Hypodontia; Ogival palate.

Introduction
Kabuki make-up Syndrome is so named because of
the characteristic facies of the affected patient. The face
is similar to a Kabuki actor’s mask, which was
traditionally used in the Japanese theatre during the Edo
period (1603-1867). This syndrome is a multiple
congenital anomaly/mental retardation syndrome that
was first described simultaneously by two groups in
Japan [Niikawa et al., 1981; Kuroki et al., 1981]. The
authors reported a group of patients who showed
characteristic facial features, skeletal anomalies,
dermatoglyphic abnormalities, short stature and mental
retardation. The frequency is about 1:32000 in Japan
[Niikawa et al., 1988]. In 1988, 62 cases were
described, 58 from Japan. Based on the findings in
these patients, the following five cardinal
manifestations were defined [Niikawa et al., 1988].
1. All patients exhibited the characteristic facies, with
eversion of the lower eyelids to the bottom, curved
eyebrow, flat nose and prominent ears.
2. In 92% of the examined sample, skeletal anomalies
were recorded such as a deformed spinal column
with or without sagittal cleft vertebrae and
Dental Institute, University of Sassari, Sassari, Italy
E-mail: giove67@yahoo.it
brachydactyly V.
3. Dermatoglyphic anomalies (fingertip pads, absence
of digital triradius c and/or d, and increased digital
ulnar loop and hypothenar loop patterns) were
described in 93% of the patients.
4. A growth deficit was observed in most of the
patients (83%) with normal birth and normal weight
at birth.
5. Cardiac anomalies were observed in one third of the
examined cases.
Similar features have also been described in other
studies, not carried out in Japan, as this syndrome is
more common than originally supposed [Braun and
Schmid, 1984; PeBenito and Ferretti, 1989; Gillis et
al., 1990; Philip et al., 1992; Burke and Jones, 1995;
Ilyina et al., 1995; Ho and Eaves, 1997; Kokitsu-
Nakata et al., 1999; Courtens et al., 2000]. A recent
report [White et al., 2004] estimates a frequency rate of
1:86000 in Australia and New Zealand. However, the
real frequency of the syndrome is under scrutiny and it
is probably similar to that observed in Japan [Adam
and Hudgins, 2005].
Several studies have described the main oral
characteristics of Kabuki Syndrome. Common
manifestations are ogival palate, labio-palatal cleft,
dental form anomalies, and hypodontia ranging 2.8% -
7.4% in the permanent dentition, less frequent in the
deciduous dentition [Balmer et al., 2001; Matsumoto

EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY • VOL. 9/3-2008 149

G. SPAN O ET AL.

and Niikawa, 2003]. No gender difference was
observed, but an aetiopathogenic hypothesis has linked
transmission of the syndrome to the X chromosome
[Niikawa et al., 1988; Li et al., 1996].
The most widely-accepted aetiopathological
hypothesis postulates a hereditary pathological
syndrome with dominant autosomal transmission, in
which each new case is a new mutation [Niikawa et al.,
1988].
There are no published data about the prevalence of
the syndrome in Italy; the aim of this report is to
describe the oral features in Kabuki Syndrome,
focusing on the tooth anomalies.
Patients and methods
Clinical evaluation
Five individuals (Fig. 1) with Kabuki Syndrome,
identified by the Child Neuropsychiatric Clinic of the
University of Sassari, Italy, agreed to participate in the
study. No similar signs were observed in any of the
families of the patients, indicating sporadic occurrence.
Medical records were reviewed and oral and dental
examinations were performed. The diagnosis was
based upon the typical pattern of malformations and
dysmorphic features (Table 1) [Matsumoto and
Niikawa, 2003].
Dental examinations were carried out under standard
conditions with plane mirror and dental probe. Dental
anomalies such as conoid teeth and agenesis were also
recorded. Occlusion status was classified following
IOTN grading.
Clinical reports
Patient 1
A girl born in 1998 after a normal term pregnancy
and normal delivery with a birth weight of 2900 g.
Impaired growth was observed at three months.
Impaired psychomotor development was detected at
the age of 23 months. A moderately severe heart defect
was diagnosed at 25 months. The girl attends a special-
needs school. Dental anomalies of 31 and 41
(hypoplasia), agenesia of 12, 22, 25, 32, 35, 45. The
maxilla was retrognathic. Several caries lesions were
noted. Anterior cross-bite and ogival palate.
Patient 2
A girl born in 1992 at the 38th week with normal
delivery and a birth weight of 2750 g, after a pregnancy
with continuous risk of miscarriage. Psychomotor
development was delayed. The girl attends a special-
needs school. Dental anomalies of 11 and 21 with a flat
screwdriver-like crown, with white spots and
hypoplasia; the upper left second incisor showed a
conical shaped crown; agenesia of 12, 14, 31, 41.
Several caries lesions observed. Bilateral cross-bite and
ogival palate.

FIG. 1 - Frontal photograph of patients with the typical features of Kabuki Syndrome.

Pa tient Sex Age Fa cies Sk eleta l M enta l Grow th Ca rdia c

Anoma lies Reta rda tion Deficit Anoma lies

1 F 9y yes yes yes yes yes

2 F 15 y yes yes yes yes nno
3 M 13 y yes yes yes yes no
4 M 21 y yes yes yes yes yes
5 F 16 y yes yes yes yes no

TABLE 1 - Vital statistics (age and gender) and main features of the five patients.

150 EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY • VOL. 9/3-2008


Patient 3
A boy born in 1994 at the 33th week with caesarean
delivery and a birth weight of 1450 g, after a
pregnancy with continuous risk of miscarriage. At
birth the patient was reanimated. Impaired growth was
observed at three months. Impaired psychomotor
development was detected at 36 months. Dental
anomalies of 11 and 21, agenesia of 12, 22, 31, 42, 44.
Several caries lesions observed. Left lateral cross-bite
and ogival palate (fig. 2).
Patient 4
A boy born in 1986 after a normal term pregnancy
and normal delivery with a birth weight of 3480 g.
Growth deficiency was observed at six months.
Impaired psychomotor development was detected at 11
months. A moderately severe heart defect was
diagnosed at 18 months. The boy attends a special-
needs school. Dental anomalies and enamel hypoplasia
of 11 and 21, the upper second incisors displayed a
conical shaped crown; agenesia of 45. Several caries
lesions observed. Bilateral cross-bite and ogival palate.
Patient 5
A girl born in 1991 after a normal term pregnancy
FIG. 2 - The oral cavity of patient 3. Dental anomalies of 11
and 21, agenesia of 12, 22, 31,42, 44. Left lateral cross-bite
and ogival palate..
FIG. 3 - The oral cavity of patient 2. A severe hypodontia.
EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY • VOL. 9/3-2008
FIVE CASE REPORTS OF KABUKI SYN DROM E
and normal delivery, birth weight 3800 g. Growth
deficiency was diagnosed at 3 years of age. Impaired
psychomotor development was detected at 45 months.
The girl attends a special-needs school. Enamel
hypoplasia of 11 and 21 was observed. Several caries
lesions observed. Anterior cross-bite and ogival palate.
Discussion
The aim of this investigation was to describe the
main oral and dental features in patients with Kabuki
Syndrome. This is a multiple malformation/mental
retardation syndrome characterised by distinctive facial
features (eversion of the lower lateral eyelid, arched
eyebrows with the lateral one-third dispersed or sparse,
depressed nasal tip and prominent ears), skeletal
anomalies, dermatoglyphic abnormalities including
persistent fingertip pads, mild to moderate mental
retardation, and postnatal growth deficiency. It is
extremely rare; in Japan, where is most frequent, it
affects 1:32000 new births. Dental anomalies are
commonly described in Kabuki Syndrome patients:
over 70% of the affected ones [Adam and Hudgins,
2005]; hypodontia is recorded in about 40% of Kabuki
patients [Lerone et al., 1997]. These clinical features
may be helpful in the diagnostic process to identify
mildly affected carrier parents.
The findings confirm the principal characteristics of
the syndrome: long palpebral fissure, lower palpebral
eversion, arched eyebrows, short nasal septum,
prominent and large ears, fingertip pads, mental
retardation, and paramedian elevation of the lower lip.
Cardiac problems are found in almost 50% of the
affected subjects. Recently several papers report that
Kabuki’s patients could be more prone to many general
medical problems like obesity and diabetes mellitus
[Fujishiro et al., 2003; Shalev et al., 2004; White et al.,
2004]. Therefore, it is essential that patients and
caregiver be aware of signs of these diseases. Kabuki
Syndrome might be associated by a weakened immune
FIG. 4 - The oral cavity of patient 4. Lateral cross bite.
151
G. SPAN O ET AL.
system, indicating therefore a high risk of infection
[Niikawa et al., 1988; Matsumoto and Niikawa, 2003;
Atar et al., 2006].
Two of the patients described in this report showed
cardiac problems. It should be emphasised that the
existence of congenital cardiac abnormalities in Kabuki
patients make them at high risk for bacterial
endocarditis and therefore administration of a
prophylactic antibiotic regimen before invasive dental
procedures is a highly advisable approach [dos Santos
et al., 2006].
Kabuki patients show mental retardation (from mild
to moderate) but they are usually self-sufficient and
with a good life skills, so they have been reported with
a relatively high level of collaboration, good memory,
friendly temperaments [White et al., 2004].
Regarding the oral and dental features, hypodontia
and associated wide spaces between teeth were
observed in patients 1, 2, 3 and 4. No tooth buds were
recorded for the lower incisors or upper lateral incisors
[Niikawa et al., 1981; Kuroki et al., 1981; Niikawa et
al., 1988; Gillis et al., 1990; Philip et al., 1992]. One of
the findings of particular concern was the very poor
oral hygiene status and evidence of EEC detected in all
our patients.
In the province of Sassari (Sardinia, Italy) the
population is estimated to be 300,000 inhabitants, of
which 56,831 [www.istat.it] in the age range of the
examined sample (9-20 years), so the estimated
prevalence of Kabuki Syndrome is 1:11600.
Conclusion
Oral/dental features in Kabuki patients could play an
important role in the understanding of the pathogenesis
of this syndrome. The contribution of dental
professionals can support and help the diagnosis of this
condition, and facilitate referral to a clinical geneticist
and to the practitioner responsible for the
comprehensive care of these patients.
References
Adam MP, Hudgins L. Kabuki syndrome: a review. Clin Genet
2005;67:209-219.
Atar M, Lee W, O’Donnell D. Kabuki syndrome: oral and general
features seen in a 2-year-old Chinese boy. Int J Ped Dent
2006;16:222-226.
Balmer RC, Mahoney E, Cameron A. Kabuki syndrome a case report
and summary of previous oral findings. Eur J Paed Dent 2001;2:83-
90.
Braun OH, Schmid E. Kabuki makeup syndrome (Niikawa-Kuroki
syndrome) in Europe. J Pediatr 1984;105:849-850.
Burke LW, Jones MC. Kabuki syndrome: underdiagnosed
recognizable pattern in cleft palate patients. Cleft Palate Craniofac
152
J 1995;32:77-84.
Courtens W, Rassart A, Stene JJ, Vamos E. Further evidence for
autosomal dominant inheritance and ectodermal abnormalities in
Kabuki syndrome. Am J Med Genet 2000;93:244-249.
dos Santos BM, Ribeiro RR, Stuani AS, de Paula e Silva FW, de Queiroz
AM. Kabuki make-up (Niikawa-Kuroki) syndrome: dental and
craniofacial findings in a Brazilian child. Braz Dent J 2006;17:249-
254.
Fujishiro M, Ogihara T, Tsukuda K. A case showing an association
between type 1 diabetes mellitus and Kabuki syndrome. Diab Res
Clin Pract 2003;60:25-31.
Gillis R, Klar A, Gross-Kieselstein E. The Niikawa-Kuroki (Kabuki
make-up) syndrome in a Moslem Arab child. Clin Genet
1990;38:378-381.
Ho HH, Eaves LC. Kabuki make-up (Niikawa-Kuroki) syndrome:
cognitive abilities and autistic features. Dev Med Child Neurol
1997;39:487-490.
Ilyina H, Lurie I, Naumtchik I, Amoashy D, Stephanenko G, Fedotov V,
Kostjuk A. Kabuki make-up (Niikawa-Kuroki) syndrome in the
Byelorussian register of congenital malformations: ten new
observations. Am J Med Genet 1995;56:127-131.
Italian Nation Institute of Statistics (ISTAT) [www.istat.it]
Kokitsu-Nakata NM, Vendramini S, Guion-Almeida ML. Lower lip pits
and anorectal anomalies in Kabuki syndrome. Am J Med Genet
1999;86:282-284.
Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. 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 1981;99:570-573.
Lai PY, Seow WK. A controlled study of the association of various
dental anomalies with hypodontia of permanent teeth. Pediatr Dent
1989;11:291-296.
Lerone M, Priolo M, Naselli A, Vignolo M, Romeo G, Silengo MC.
Ectodermal abnormalities in Kabuki syndrome. Am J Med Gen
1997;73:263-266.
Li M, Zackai EH, Niikawa N, Kaplan P, Driscoll DA. Kabuki syndrome
is not caused by a microdeletion in the DiGeorge/velocardiofacial
chromosomal region within 22q 11.2. Am J Med Genet 1996;65:101-
103.
Matsumoto N, Niikawa N. Kabuki make-up syndrome: a review. Am J
Med Genet C Semin Med Genet 2003;117:57-65.
Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-
up syndrome: a syndrome of mental retardation, unusual facies, large
and protruding ears, and postnatal growth deficiency. J Pediatr
1981;99:565-569.
Niikawa N, Kuroki Y, Kajii T, Matsuura N, Ishikiriyama S, Tonoki H,
Ishikawa N, Yamada Y, Fujita M, Umemoto H, et al. Kabuki make-
up (Niikawa-Kuroki) syndrome: a study of 62 patients. Am J Med
Genet 1988;31:565-589.
PeBenito R, Ferretti C. Kabuki make-up syndrome (Niikawa-Kuroki
syndrome) in a black child. Ann Ophthalmol 1989;21:312-315.
Philip N, Meinecke P, David A, Dean J, Ayme S, Clark R, Gross-
Kieselstein E, Hosenfeld D, Moncla A, Muller D, et al. Kabuki make-
up (Niikawa-Kuroki) syndrome: a study of 16 non-Japanese cases.
Clin Dysmorphol 1992;1:63-77.
Shalev SA, Clarke LA, Koehn D. Long-term follow-up of three
individuals with Kabuki syndrome. Am J Med Gen 2004;125:191-
200.
White SM, Thompson EM, Kidd A, Savarirayan R, Turner A, Amor D,
Delatycki MB, Fahey M, Baxendale A, White S, Haan E, Gibson K,
Halliday JL, Bankier A. Growth, behavior, and clinical findings in 27
patients with Kabuki (Niikawa-Kuroki) syndrome. Am J Med Genet
A 2004;127:118-127.
EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY • VOL. 9/3-2008