J Tokyo
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63 (Extra)
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TEN PATIENTS WITH KABUKI MAKE-UP
(NIIKAWA-KUROKI) SYNDROME
Miyako OGUNI'), Hiroshi MARUYAMAi)2), Hirokazu OGUNI'),
Kayoko SAITO'} and Yukio FUKUYAMA')
i)Department of Pediatrics, Tokyo Women's Medical College
2)Matsudo Clinic
(Received June 22, 1993)
Introduction
The term Kabuki make-up syndrome was first
coined by Kuroki and Niikawa, working indepen-dently, in 1981i}2). Subsequently, several cases have been reported in Japan3)ny7) and several more
in other countries8}nyi2).
Characteristics of this syndrome include a
peculiar. facial appearance: eversion of the lower lateral eyelid, arched eyebrows ･with the lateral
one third having sparse or dispersed hair, a
depressed nasal tip, and prominent ears. Skeletal
anomalies and dermatoglyphic abnormalities are
very comrnon, and mental retardation is present
in all cases.
The derMatoglyphic pattern described by
Niikawa et al'3> in 1982 included an increased
digital ulnar loop and hypothenar loop patterns,
absence of the digital triradius c and/or d, and the presence of fingertip pads.
We experienced 10 cases of this syndrome, four
of whom had also xeroderma pigmentosum. We
report here the clinical details of our 10 Kabuki
make-up syndrome cases.
Subjects
Ten patients with Kabuki make-up syndrome
were identified among the patients followed at
Matsudo Clinic (Table). Dermatoglyphic and
cytogenetic studies (Giemsa-trypsin banded pe-ripheral lymphocyte chromosomes), and roent-gengrams of the spinal column and hands were
obtained from all of these patients. Detailed
in-dividual past histories and family histories were provided by their parents.
Results
In addition to the typical craniofacial anomalies (Figure), case 1 had dermatoglyphic abnormalities,
short fifth fingers, hip dislocation, hearing loss,
obesity, epilepsy, and xeroderma pigmentosum.
Case 2 had short fifth fingers, cleft palate, obesity,
and a VSD, but no dermatoglyphic abnorm'alities.
Case 3 had dermatoglyphic abnormalities,
stra-bismus, short fifth fingers, a rib anbmaly, and
xeroderma pigmentosum. Case 4 had one
dermato-glyphic abnormality, strabismus, short fifth
fingers, and epilepsy. Case 5, who was 45,X had
one dermatoglyphic abnormality, strabismus,
short fifth fingers, epilepsy, and xeroderma
pig-mentosum. Case 6 had two dermatoglyphic
ab-normalities, .strabismus, cleft palate, hipdisloca-tion, blue sclerae, epilepsy and xeroderma pig-mentosum, but no shortening of finger V. Case 7
had two dermatoglyphic abnormalities,
strabis-mus, short fifth fingers, ASD, VSD, epilepsy and
xeroderma pigmentosum. Case 8 had two
der-matoglyphic abnormalities, blue sclerae, and
epilepsy. Case 9 had dermatoglyphic
abnormali-ties, obesity, strabismus, and epilepsy, but no shortening of finger V. Case 10 had one dermato-glyphic abnormality, and epilepsy, but no shorten-.ing of finger V. Cases 1 to 5 had definite lower palpebral eversion, while cases 6 to 10 had only
mild eversion. Cases 9 and 10 had arched
eye-brows but the pattern of hair growth was
-El18-Table Ten cases of Kabuki make・up syndrome Case 1 2 3 4 5 6 7 8 9 10 Manifestations Sex F F
M
F F FM
M
FM
Age（Years） 23 13 15 14 11 17 11 14 10 7Mental retardation severe severe mild moderate mlld severe severe severe moderate mild
Chromosome 46，XX 46，XX 46，XY 46，XX 45，X 46，XX 46，XY 46，XY 46，XX 46，XY
Craniofacial anornalies Lower palpebra玉eversion 十 十 十 十 十 十 十 十 十 十 Arched eyebrows with sparse 十 十 十 十 十 十 十 十 十 十 1ateral 1／3 Prominent ears 十 十 十 十 十 十 十 十 一 Depressed nasa王tip 十 十 十 十 一 十 十 十 十 一 Ear malfQrmatiGns 一 十 十 一 十 十 十 一 一 Abnormal dentition 十 十 十 十 十 一 十 十 『 Spaced teeth 十 十 十 十 十 十 十 ㎜ High−arched palate 十 一 一 十 十 十 一 十 一 一 Epicanthus 十 一 十 十 十 十 十 十 十 十 Strabismus ｝ 十 十． 十 十 十 ㎜ 十 一 Cleft palate／lip 一 十 』 一 一 十 一 一 Preauricular dimple 一 一 『 一 一 一 ｛ 『 Micrognathia 『 一 一 一 一 』 一 一 一 Skeletal abnormalities Short丘nger（V） 十 十 一 十 十 一 十 一 一 Short middle phalanx（V） 十 一 十 十 十 一 十 十 一 一 Scoliosis 十 『 十 一 十 十 一 一 一 Rib anomaly 『 一 十 』 一 一 『 『 一 Hip dislocation 十 一 十 ｝ 十 一 一 一 一 Foot deformity 十 十 十 十 十 十 十 十 十 十 Short stature 十 一 十 一 十 十 一 一 『 Occasional anomalies Cardiovascular anomaly 十 一 一 ｝ 『 十 一 一 一 Blue sclerae 十 『 『 十 一 十 一 十 一 一 Undescended testis ｝ 一 一 一 一 』 一 一 一 一 Complications Susceptibility to infection 十 十 一 十 一 十 十 一 十 十 Recurrent otitis media 十 一 』 十 一 『 『 一 ｝ Hearing loss 十 一 『 一 一 一 一 一 Obesity 十 十 ｝ 一 一 一 一 ｝ Seizure 十 一 十 十 十 十 十 十 十 Xeroderma pigmentosum 十 十 一 十 十 『 一 一 一 Dermatoglyphic丘ndings Increased ulnar looPs 十 一 十 一 十 一 十 十 Absence of digital triradius c 一 一 十 十 一 十 Absence of digital triradius d 十 十 十 一 『 十 十 一 Increased hypothenar loops 十 一 『 一 十 十 十 十 一 Presence of fingertip pads 十 十 十 十 十 十 十 十 十 十 sentially norma1． Of the 10 patients， six were female and four were male。 Their ages at the time of study ranged from 7 to 23 years with a mean of 14 years． The prenatal an∼l perinatal histories of these patients were non contributory． Weight， height．and head circumference values at birth were all with孟n normal range． In the postnatal per量od， six patients had experienced difficulty in feeding which lead to failure to thrive and delayed development． S三x 一E119一
1 2 3 4 5
6 7
Figure
8 9
Ten patients of Kabuki make-up syndrome: Facial appearance
10
er . .. `'W
patients (60%) had short stature, in the -2.3 SD to
-5.1 SD range. Heights of the remaining 4 pa-tients (40%) were within normal range. All 10
patients were mentally retarded: 5 severely, 2 moderately and, the remaining 3 mildly.
All had the characteristic peculiar face; lower palpebral eversion and arched eyebrows, foot de-formities and dermatoglyphic abnormalities with
fingertip pads. Seven of these patients had a short
nasal septum, prominent ears, depressed nasal
tip, abnormal dentition, spaced teeth, epicanthus
and susceptibility to infection. Six had strabismus
and a short middle fifth phalanx bilaterally, and
five had a high arched palate, scoliosis and short fifth fingers. Cleft palate was present in 3 cases,
congenital cardiac anomalies in two: one had ASD
and PDA, and the other had VSD and a rib
anomaly (11 ribs).
Noteworthy complications included epilepsy
(8 cases) and xeroderma pigmentosum (4 cases). Among the 8 cases with epilepsy, 3 had alized tonic clonic seizure (GTCS), 3 had gener-alized tonic seizure (GTS), 2 had complex partial seizure (CPS), and 1 had simple partial seizure
(SPS). One had both GTCS and CPS. In three of
these cases, seizure control was difficult.
Giemsa-trypsin (G) was used to analyze periph-eral lymphocyte chromosomes of all patients and the only anomaly found was in the 45,X patient. There was consanguinity on the paternal side in one case. As to family history, three cases had neurological disorders within the family: autism, epilepsy and hydrocephalus in one family each.
None had a family history of Kabuki make-up
syndrome.
Discussion
Our 10 patients all had a peculiar facial
appear-ance with skeletal and dermatoglyphic anomalies,
compatible with Kabuki make-up syndrome, as
reported by Kuroki and Niikawa. Unlike Kuroki and Niikawa's cases, half of our patients had
severe mental retardation. In addition the
'
plications of epilepsy and xeroderma pigmento-sum were rnore prevalent in our cases.
Types of seizures, seizure onset, EEG findings and response to treatment were variable.
Four of our 10 patients had xeroderma
pig-mentosum, an exceptional complication in this
disease. The unusual combination of Kabuki
-E120-make-up syndrome and this dermatologic disorder has not previously been reported, to our
knowl-edge. Xeroderma pigmentosum is an autosomal
recessive disease characterized by cutaneous
photosensitivity, a decreased ability to repair
deoxyribonucleic acid (DNA) damaged by
ultra-violet radiationi`). Children with xeroderma
pig-mentosum develop erythema, freckling, and
in-creased pigmentation after exposure to sunlight.
The onset of most cases is in early childhood.
Genetic analysis of cultured cells from xeroderma
pigmentosum patients has revealed the presence of 8 complementation groups, all showing a
de-ficiency in the excision of UV-induced lesions in
the DNA. Excision repair cross complementing
<ERCC) chrornosomal loci -1, 2, 3, 4, 5 and6 have
been identifiedi5)Ni7).
Although Kabuki make-up syndrome seems to
be congenital, the association of other major
anomalies was variable and no common origin
could be identified. Congenital heart disease, cleftpalate, and other abnormalities can be induced in
early pregnancy, while minor facial anomalies may develop in later pregnancy. In addition to
these findings, abnormal dermatoglyphics, scolio-sis and short stature, which became more
promi-nent over time, were evident. There were no
familial cases among our patients. There has been
only one case report describing familial occurrence
of Kabuki make-up syndrome, in two siblings and
their father8). As Niikawa et al suggested3), Kabuki
make-up syndrome may be an autosomal
domi-nant disorder in which the majority of patients
have a new mutation, because virtually all
pa-tients encountered to date have been sporadic and only one had known affected family members. Several institutions have reported patients with
Kabuki make-up syndrome accompanying sex
chromosomal abnormalities, such as 45,X6)7). Wealso found one case with a ring X chromosome
(45,X). In addition, we have four cases of
xero-derma pigmentosum with this syndrome. These
facts may offer clues as to the role of chromosomalanomalies in Kabuki make-up syndrome. As yet,
however, results are inconclusive.
Further clinical and molecular studies are
necessary to elucidate the cause of this syndrome.
References
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12) Braun OH, Schmid E: Kabuki make-up syndrome
(Niikawa-Kuroki syndrome) in Europe.J Pediatr 105: 849-850, 1984
13) Niikawa N, Kuroki Y, Kajii T: The dermatqglyphic pattern of the Kabuki make-up syndrome. Clin Genet 21: 315-320, 1982
14) Patton LL, Valdez IH: Xeroderma pigmentosum:
Review and report of a case. Oral Surg Oral Med Oral Pathol 71: 297-300, I991
15) Bootsma D: The genetic basis of xeroderma sum. Ann Genet 34: 143-I50, 1991
16) Tanaka K, Miura N, Satokata I: Analysis of a
huTpan DNA excision repair gene involved in group A xeroderma pigmentosum-and containing a zinc-finger
- domain． Nature 348：73−76，1990 17）Weeda G， Wiegant J， Van Der Ploeg M：L㏄aliz研 tion of the xeroderma pigmentosum group B−correcting gene ERCC3 to human chromosome 2q 21． Genomics 10：1035−1040，1991 歌舞伎メーキャップ症候群の10例 1凍京女子医科大学 小児科，2）松戸クリニック オグニミ ヤ コ マルヤマ ヒロシ オグニ ヒロカズ 小国美也子1）・丸山 博1）2）・小国 弘量1） サイトウカ ヨ コ フクヤマ ユキォ 斎藤加代子1）・福山 幸夫1） 歌舞伎メーキャップ症候群は，1981年黒木らおよび新川らによって初めて記載された．我々は，10 例の歌舞伎メーキャップ症候群を経験したので報告する．7歳から23歳までの女6例，男4例である． 10例とも切れ長眼裂，下眼裂の外反，外側1／2の粗な弓状眉毛という特徴的顔貌を呈しており，手掌紋
