Alternative titles; symbols
SNOMEDCT: 313426007; ORPHA: 2322; DO: 0060473;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.12 | Kabuki syndrome 1 | 147920 | Autosomal dominant | 3 | KMT2D | 602113 |
A number sign (#) is used with this entry because Kabuki syndrome-1 (KABUK1) is caused by heterozygous mutation in the MLL2 gene (KMT2D; 602113) on chromosome 12q13.
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).
Genetic Heterogeneity
Kabuki syndrome-2 (300867) is caused by mutation in the KDM6A gene (300128) on chromosome Xp11.
Niikawa et al. (1988) collected data from 62 patients with Kabuki syndrome from 33 institutions, almost all of them in Japan. Most of the patients had 5 cardinal manifestations: (1) a peculiar face in all cases, characterized by eversion of the lower lateral eyelid, arched eyebrows with sparse or dispersed lateral one-third, depressed nasal tip, and prominent ears; (2) skeletal anomalies in 92%, including brachydactyly V and spinal deformity with or without sagittal cleft vertebrae; (3) dermatoglyphic abnormalities in 93%, including increased digital ulnar loop and hypothenar loop patterns, absence of the digital triradius c and/or d, and presence of fingertip pads; (4) mild to moderate mental retardation in 92%; and (5) postnatal growth deficiency in 83%. Fetal finger pads, which are typical of Kabuki syndrome, occur also in the FG syndrome (305450). Early breast development occurred in 23% of infant girls. Congenital heart defects, including single ventricle with a common atrium, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of aorta, patent ductus arteriosus (see 607411), aneurysm of aorta, transposition of great vessels, and right bundle branch block, were observed in 31% of the patients. Of the 62 Kabuki syndrome patients, 58 were Japanese. The incidence of the disorder in Japanese newborns was estimated at 1 in 32,000. All cases were sporadic. The sex ratio was even, and there was no correlation with birth order. Consanguinity was not increased among the parents, and no exogenous agent could be incriminated. Three of the 62 patients had a Y chromosome abnormality involving Yp11.2. In general, the findings of Niikawa et al. (1988) were considered compatible with an autosomal dominant disorder in which each patient represents a fresh mutation. A mutation rate was calculated at 15.6 x 10(-6) per gamete per generation. (The abstract of Niikawa et al. (1988) incorrectly stated the rate to be 15.6 x 10(6).) The possibility of the location of the gene in the pseudoautosomal region of the X chromosome was also raised.
Clarke and Hall (1990) described 3 unrelated Caucasian children with this syndrome. Gillis et al. (1990) described the disorder in a child of Arab descent. Philip et al. (1992) studied 16 non-Japanese cases from Europe and North America. They concluded that the facial phenotype is specific and easily recognizable regardless of ethnic origin. Postnatal growth retardation and mild mental retardation were confirmed to be cardinal manifestations. Significant neurologic dysfunction other than mental retardation and joint hypermobility appeared to be more common in the non-Japanese patients.
Hughes and Davies (1994) presented 20 unselected cases with a definitive diagnosis of Kabuki syndrome: 6 boys and 14 girls, ranging in age from 10 months to 13 years. The incidence of heart abnormalities in these children was almost twice that previously reported (55%) and juxtaductal coarctation occurred with a frequency of 25%. One of the patients pictured by Hughes and Davies (1994) showed the accentuated depression that is often seen below the midpoint of the lower lip.
Ilyina et al. (1995) reported 10 patients of European ancestry from Byelorussia, Russia, and Moldavia. They emphasized prominent and broad philtrum as an important component. Some clinical manifestations were observed in parents and other relatives in 3 generations of 3 families. Ilyina et al. (1995) favored autosomal dominant inheritance with variable expressivity.
Burke and Jones (1995) reported 8 cases of Kabuki syndrome in non-Japanese patients. They commented that the phenotype appears to evolve over time, making the diagnosis difficult in infancy. They stated that cleft palate occurs in about 40% of patients. Galan-Gomez et al. (1995) described Kabuki syndrome in 5 Spanish children, 3 females and 2 males. Sagittal vertebral clefts and dermatoglyphic abnormalities were present in all 5; general heart defects were present in 4.
Halal et al. (1989) reported an instance of probable autosomal dominant inheritance of Kabuki syndrome; a father and his 2 children were affected. The father had milder symptoms than the offspring, but had typical facial changes and was of normal intelligence. Kobayashi and Sakuragawa (1996) described a nonconsanguineous family in which a 45-year-old man and his 17-year-old daughter were affected. The father had characteristic facial abnormalities of Kabuki syndrome, including long palpebral fissures, long eyelashes, and a prominent nose. He was of normal stature and there were no deformities of the fingers, feet, or ribs. However, he had all ulnar loop patterns on the fingertips, and lacked palmar triradii c and d. His mental status was above average. In the daughter, a ventricular septal defect had been surgically closed at age 6 years. Her psychomotor development was delayed and school performance was poor. She was 146.5 cm tall at the age of 17. She had epicanthic folds, long palpebral fissures, high-arched eyebrows that were sparse in the lateral one-third, a broad and depressed nasal tip, a short nasal septum, and large malformed ears. Her fingers were stubby with bilateral clinodactyly of the fifth fingers, and the first toes were hyperplastic. On fingertips she had an increased number of ulnar loops, and she lacked palmar triradii c and d. There was a hypothenar ulnar loop, and fingertip pads were found on all fingers, a common finding in Kabuki syndrome. Her IQ was estimated to be 60. The mother was of normal height and had no minor anomalies or abnormal dermatoglyphic patterns.
Silengo et al. (1996) reported an Italian girl with typical findings of Kabuki syndrome and a mildly affected mother. The fact that males and females are equally affected, that the consanguinity rate is not increased, that parents and other relatives of patients show a facial resemblance, and that the condition is transmitted vertically with variable clinical manifestations in familial cases are all compatible with autosomal dominant inheritance. Sporadic cases may represent new mutations.
Tsukahara et al. (1997) described 4 individuals with Kabuki syndrome in 2 families. In family 1, the proposita, a 2-year-old girl, and her mother had typical Kabuki syndrome. The proposita also had early breast development. In family 2, the proposita, a 6-month-old girl, and her mother had typical Kabuki syndrome. The proposita died at age 6 months as a result of complications of a cardiac malformation.
In a girl with Kabuki syndrome, Lerone et al. (1997) described conical incisors, hypodontia, hypoplastic nails, and brittle hair. Although abnormal teeth have commonly been described in this disorder, hair abnormalities have never been investigated.
Dominant inheritance with variable expressivity was supported by the mother and child reported by Courtens et al. (2000). The 18-month-old daughter had facial features characteristic of Kabuki syndrome, prominent fingertips, a midsagittal cleft of vertebral body thoracic-4, hypotonia, and psychomotor retardation. The mother had a similar facial appearance, prominent, cup-shaped ears, abnormal dentition, early breast development, and low normal intelligence. The maternal grandmother had the same facial appearance and 3 maternal aunts reportedly likewise showed these features. Microscopic examination of the hair of the proposita showed abnormalities consisting of trichorrhexis nodosa, twisting of the hair shafts, and irregularity of the diameter of the hair, all changes similar to those reported by Lerone et al. (1997).
Shotelersuk et al. (2002) described 6 Thai children with the Kabuki syndrome, including monozygotic twins who are discordant for the syndrome. In another family, a mother had a facial appearance similar to that of her affected son, suggesting autosomal dominant inheritance. Common findings included lower lip pits with or without symmetrical lower lip nodules and pilonidal sinuses. Early eruption of the 2 lower central incisors, transient hyperthyrotropinemia in infancy, and aplasia cutis were also observed.
Wilson (1998) compared 8 new and 5 previously illustrated cases of this syndrome with those in the literature, providing data on 183 cases. A total of 108 non-Asian patients had been reported.
Although hydronephrosis had been reported in a few cases of Kabuki syndrome, Ewart-Toland et al. (1998) reported the first cases of Kabuki syndrome with hepatic anomalies. They described 2 patients with renal and/or hepatic anomalies requiring transplantation. Both patients had the characteristic facial appearance of children with Kabuki syndrome, postnatal growth deficiency, and developmental delay. At birth, 1 patient presented with hypoglycemia, ileal perforation, right hydroureter, and hydronephrosis. The patient subsequently developed hyperbilirubinemia, hepatic abscess, and cholangitis. At age 8 months, he underwent a liver transplant. Hepatic pathology was interpreted as neonatal sclerosing cholangitis. Case 2 presented with renal failure at age 6 years. Renal ultrasound showed markedly dysplastic kidneys requiring transplantation. In addition to characteristic findings of Kabuki syndrome, she had coronal synostosis and was shown to have immune deficiency and an autoimmune disorder manifesting as Hashimoto thyroiditis and vitiligo.
Kawame et al. (1999) analyzed the clinical findings of Kabuki syndrome in 18 North American children. Most had postnatal growth retardation, and all had developmental delay and hypotonia. Feeding difficulties, with or without cleft palate, were common; 5 patients required gastrostomy tube placement. In all but 2 patients, developmental quotients/IQs were 60 or less. Seizures were seen in less than half of the patients, but ophthalmologic and otologic problems were common, particularly recurrent otitis media. Congenital heart defects were present in 7 (39%); 3 patients underwent repair of coarctation of the aorta. Other features included urinary tract anomalies, malabsorption, joint hypermobility and dislocation, congenital hypothyroidism, idiopathic thrombocytopenic purpura, and, in 1 patient, autoimmune hemolytic anemia and hypogammaglobulinemia. All patients had negative family histories for Kabuki syndrome.
McGaughran et al. (2000) described 2 females with typical Kabuki syndrome who presented in the first year of life with extrahepatic biliary atresia, a previously undescribed complication of the syndrome. Selicorni et al. (2001) described a similar case of atresia of the extrahepatic bile ducts and common bile duct identified in a 44-day-old infant. A Kasai procedure was performed at that time with complete disappearance of jaundice by the age of 5 months. However, recurrence of symptoms required liver transplantation which was successfully performed at the age of 20 years; she was in good condition 5 years thereafter.
Donadio et al. (2000) reported an Italian girl with Kabuki syndrome and diaphragmatic hernia. Donadio et al. (2000) reviewed 3 other cases of Kabuki syndrome with diaphragmatic defects, all of non-Asian origin.
Van Haelst et al. (2000) reported 2 patients with Kabuki syndrome and stenosis of the central airways (one with local stenosis of the right upper lobe bronchus, and the other with severe bronchomalacia and an abnormal right bronchial tree), a complication not previously reported in patients with Kabuki syndrome. One of the patients also had extrahepatic biliary atresia, and the other had congenital diaphragmatic hernia.
Kokitsu-Nakata et al. (1999) reported the case of a Brazilian girl with Kabuki syndrome associated with lower lip pits and anorectal anomalies. They found reports of at least 4 patients with Kabuki syndrome and anorectal anomalies (Matsumura et al., 1992). They found reports of lower lip pits only in a Kabuki syndrome patient reported by Franceschini et al., 1993. However, Makita et al. (1999) reported a 5-year-old Japanese girl with clinical manifestations of both Kabuki syndrome and the van der Woude lip-pit syndrome (VWS; 119300). Assuming that the association of the 2 syndromes was caused by a microdeletion involving putative genes for the 2 disorders, Makita et al. (1999) carried out fluorescence in situ hybridization and microsatellite analyses using PAC clones and dinucleotide repeat markers spanning the VWS1 critical region at 1q32-q41. No deletion was detected.
Igawa et al. (2000) studied 3 patients with Kabuki syndrome for middle and inner ear abnormalities by using CT of the petrous bones. No middle ear abnormalities were identified, but all 3 patients had bilateral dysplasia of the inner ear (hypodysplasia of the cochlea, vestibule, and semicircular canals). Audiometry on 2 of the patients showed a sharp decrease in hearing of the high tone range, bilateral in one and unilateral in the other. The authors concluded that CT of the petrous bones and audiometry should be performed in early infancy on all patients with Kabuki syndrome.
Matsune et al. (2001) described oral manifestations in 6 patients with Kabuki syndrome. These included a high-arched palate, malocclusion, microdontia, a small dental arch, hypodontia, severe maxillary recession, and midfacial hypoplasia.
McGaughran et al. (2001) described 9 patients with Kabuki syndrome from New Zealand, all having the characteristic facial dysmorphism and many of the well-described associated anomalies. Some had unusual abnormalities, including diaphragmatic eventration, severe congenital mitral stenosis, idiopathic thrombocytopenic purpura, and vitiligo. They also reported Arnold Chiari type 1 malformation and epibulbar dermoids, neither of which had been previously reported in this syndrome.
Digilio et al. (2001) presented the results of cardiac evaluations of 60 patients diagnosed with Kabuki syndrome at their institution. Cardiac evaluation included chest radiograph, electrocardiogram, and 2-dimensional and color Doppler echocardiography. Thirty-five of the patients (58%) had congenital heart defects. The most commonly observed defects were coarctation of the aorta (23%), atrial septal defect (20%), and ventricular septal defect (17%).
Kurosawa et al. (2002) reported 4 patients with Kabuki syndrome and patellar dislocation and reviewed 6 previously reported patients with this combination. In their 4 patients, the age at diagnosis of the patellar dislocation ranged from 11 to 23 years. Of the patients in whom gender was known, 7 were female and 2 were male. The authors concluded that patellar dislocation may be frequent among older children and young adults with Kabuki syndrome, especially among obese female patients with lax knee joints.
Fryns and Devriendt (1998) described an 8-year-old girl with signs and symptoms thought to be consistent with Kabuki syndrome. She also had bilateral defective, bipartite clavicles. Hinrichs et al. (2002) described 2 unrelated patients with this type of clavicular defect in association with Kabuki syndrome.
Mihci et al. (2002) described a 7-year-old boy with Kabuki syndrome whose head MRI showed migration defects, including periventricular nodular heterotopia present along the walls of both lateral ventricles and an underdeveloped corpus callosum.
Ming et al. (2003) reported 3 children with Kabuki syndrome who also had retinal coloboma. A diagnosis of CHARGE association (214800) was initially suggested in 2 of the patients before the typical facial features of Kabuki syndrome emerged. A review of reported cases showed that the incidence of coloboma is greatly increased in Kabuki syndrome.
White et al. (2004) documented the phenotype of 27 children and adults with Kabuki syndrome from Australia and New Zealand. Parents reported a behavior phenotype characterized by the avoidance of eye contact, a love of music, and an excellent long-term memory. There was no correlation between head circumference and severity of intellectual disability. Six of their patients showed a characteristic growth profile, with failure to thrive in infancy progressing to obesity or overweight in middle childhood or adolescence.
Wessels et al. (2002) reviewed the characteristics of Kabuki syndrome in 300 patients. Typical findings included mild to moderate mental retardation, fetal pads, cleft palate, and characteristic facies with long palpebral fissures, everted lower lateral eyelids, and arched eyebrows. Postnatal growth retardation and skeletal and visceral anomalies were present in a large percentage of the patients.
Genevieve et al. (2004) described 8 patients from a series of 20 who had atypical findings in Kabuki syndrome. Rare or atypical features included the following: chronic and/or severe diarrhea (4/20) including celiac disease, diaphragmatic defects (3/20), pseudarthrosis of the clavicles (2/20), vitiligo (2/20), and persistent hypoglycemia (2/20). Other occasional findings were severe autoimmune thrombopenia, cerebellar vermis atrophy, and myopathic features. One patient presented with a clinical overlap with CHARGE syndrome (214800).
Adam and Hudgins (2005) provided a detailed review of the clinical features, diagnostic criteria, and cytogenic abnormalities reported in Kabuki syndrome.
Turner et al. (2005) reported 7 patients with Kabuki syndrome. Three patients had previously undetected ocular abnormalities, including myopia, ptosis, strabismus, and tilted discs. Four patients had nocturnal lagophthalmos (sleeping with the eyes open). There was no evidence of an 8p duplication in any of the patients.
Hoffman et al. (2005) performed immunologic evaluation of 19 consecutive individuals with Kabuki syndrome and found decreased IgA levels in 15 of 19 patients (79%), 2 of whom had undetectable levels. Eight patients (42%) also had low total IgG levels, and specific IgG subclass abnormalities were found in 6 of 13 patients evaluated; IgM levels were less frequently decreased. One patient failed to generate anti-tetanus antibodies despite immunization. Hoffman et al. (2005) suggested that hypogammaglobulinemia is a frequent finding in Kabuki syndrome and noted that the pattern of antibody abnormalities resembles common variable immune deficiency (CVID; 240500).
Ruault et al. (2020) evaluated growth parameters and generated growth curves from a French cohort of 95 patients (54 males and 41 females) with Kabuki syndrome. Five percent of the patients had intrauterine growth retardation. Thirty-five of the 89 patients (39%) for whom information was available demonstrated postnatal growth retardation, with height below -2 SD. Evaluation of patient height with respect to parental target size demonstrated no difference in height attainment between those patients treated with growth hormone and those who were not. Ruault et al. (2020) also found that 32% of the patient population had microcephaly and 21% had obesity during childhood.
Daly et al. (2020) reported a patient with microcephaly who had a brain MRI at 5 days of age that showed lobar holoprosencephaly, partial agenesis of the corpus callosum, and incomplete separation of the deep gray matter structures. She had 3 episodes of bronchiolitis by 6 months of age. At 5 months of age she was diagnosed with central diabetes insipidus. She had seizures starting at 7.5 months of age. On examination at 2 years of age, she had long palpebral fissures, everted lower eyelids, arched eyebrows, and large protruding ears.
Adam et al. (2019) reported consensus diagnostic criteria for Kabuki syndrome that were developed by an international group of experts after a systematic review of the literature. The authors proposed that a definitive diagnosis could be made in a patient at any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in KMT2D or KDM6A; and (2) typical dysmorphic features at some point of life. Typical dysmorphic features included long palpebral fissures with eversion of the lateral third of the lower eyelid and 2 or more the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent, or cupped ears; and (4) persistent fingertip pads. Criteria for probable and possible diagnoses were also included.
Kabuki syndrome is estimated to occur in at least 1 per 32,000 Japanese individuals (Niikawa et al., 1988).
Li et al. (1996) excluded microdeletion within 22q11.2 as a causative factor of the syndrome in 5 patients (3 Japanese children, a German girl, and a Colombian boy). The region was chosen for study because of the presence of congenital heart defects in patients with Kabuki syndrome and speculation that the condition might have a common molecular cause with the 22q11.2 deletion syndromes, DiGeorge syndrome (188400) and velocardiofacial syndrome (192430).
Lo et al. (1998) found an interstitial duplication of the short arm of chromosome 1 with breakpoints involving 1p13.1 and 1p22.1 in a patient with some features suggesting Kabuki syndrome, i.e., mental retardation, small head, eversion of the lateral part of the lower eyelids, epicanthic folds, lateral flare of the eyebrows, short columella, and persistent fetal finger pads. Other chromosome abnormalities described in this disorder, usually as isolated cases, were reviewed.
Using comparative genomic hybridization (CGH), Milunsky and Huang (2003) found an 8p23.1-p22 duplication in 6 unrelated patients with Kabuki syndrome. They delimited the duplicated region in all cases to approximately 3.5 Mb by BAC-FISH analysis. No duplication of this region was found in 2 parents or 20 controls by either CGH or BAC-FISH. Because the 6 patients with Kabuki syndrome represented different races, the authors suggested that the duplication may represent a common etiologic basis for the disorder.
By FISH using 15 BAC clones covering 8p23.1-p22, Miyake et al. (2004) did not detect any duplication in 26 Japanese and 2 Thai patients with Kabuki syndrome. Based on examination of the facial photographs of cases 1 and 2 in the report by Milunsky and Huang (2003), Miyake et al. (2004) suggested that the patient populations studied may differ clinically, with the earlier reported patients having an 'atypical Kabuki syndrome.'
Using array-based comparative genomic hybridization and FISH, Hoffman et al. (2005) failed to detect a duplication of 8p23.1-p22 in 15 patients with Kabuki syndrome and suggested that the 8p duplication may not be a common mechanism for Kabuki syndrome.
The transmission pattern of KABUK1 in the families reported by Ng et al. (2010) and Hannibal et al. (2011) was consistent with autosomal dominant inheritance. In most of the cases in which DNA was available from both parents, the mutation was confirmed to be de novo.
Ng et al. (2010) performed the exome sequencing of 10 unrelated patients with Kabuki syndrome, 7 of European ancestry, 2 of Hispanic ancestry and 1 of mixed European and Haitian ancestry, and identified nonsense or frameshift mutations in the MLL2 gene in 7 patients. Follow-up Sanger sequencing detected MLL2 mutations in 2 of the 3 remaining individuals with Kabuki syndrome and in 26 of 43 additional cases. In all, they identified 33 distinct MLL2 mutations in 35 of 53 families (66%) with Kabuki syndrome (see, e.g., 602113.0001-602113.0004). In each of 12 cases for which DNA from both parents was available, the MLL2 variant was found to have occurred de novo. MLL2 mutations were also identified in each of 2 families in which Kabuki syndrome was transmitted from parent to child. None of the additional MLL2 mutations was found in 190 control chromosomes from individuals of matched geographic ancestry. Ng et al. (2010) suggested that mutations in MLL2 are a major cause of Kabuki syndrome.
Hannibal et al. (2011) identified 70 mutations in the MLL2 gene in 81 (74%) of 110 kindreds with Kabuki syndrome. In simplex cases for which DNA was available from both parents, 25 mutations were confirmed to be de novo, whereas a transmitted mutation was found in 2 of 3 familial cases. Most of the variants were nonsense or frameshift mutations predicted to result in haploinsufficiency. Mutations occurred throughout the gene, but were particularly common in exons 39 and 48. The clinical features of those with or without mutations were similar, except for renal anomalies, which occurred in 47% of mutation carriers compared to 14% of those who did not have a mutation.
Li et al. (2011) sequenced all 54 coding exons of the MLL2 gene in 34 patients with Kabuki syndrome and identified 18 distinct mutations in 19 patients; 11 of 12 tested de novo. Mutations were located throughout the gene and included 3 nonsense mutations, 2 splice site mutations, 6 small deletions or insertions, and 7 missense mutations. Li et al. (2011) compared frequencies of clinical symptoms in MLL2 mutation carriers versus noncarriers. MLL2 mutation carriers more often presented with short stature and renal anomalies (p = 0.026 and 0.031, respectively), and in addition, MLL2 showed a more typical facial gestalt (17 of 19) compared with noncarriers (9 of 15), although this result was not statistically significant (p = 0.1).
Miyake et al. (2013) identified MLL2 mutations in 50 (61.7%) of 81 patients with Kabuki syndrome. Most (70%) of the MLL2 mutations were predicted to be protein-truncating. The truncating mutations were distributed throughout the coding region, whereas the nontruncating mutations were most often within or adjacent to functional domains.
Using direct sequencing, MLPA, and quantitative PCR, Micale et al. (2014) screened 303 patients with Kabuki syndrome and identified 133 KMT2D mutations, 62 of which were novel. Micale et al. (2014) found that a number of KMT2D truncating mutations result in mRNA degradation through nonsense-mediated mRNA decay, contributing to protein haploinsufficiency. The authors also demonstrated that the reduction of KMT2D protein levels in patients' lymphoblastoid and skin fibroblast cell lines carrying these mutations affects the expression levels of known KMT2D target genes.
Van Laarhoven et al. (2015) identified KMT2D mutations in 12 (32%) of 40 patients clinically diagnosed with Kabuki syndrome.
Cocciadiferro et al. (2018) evaluated mutations in the KMT2D gene in 505 patients with Kabuki syndrome. A total of 208 mutations in KMT2D were identified in 196 patients. The mutations included 54 nonsense, 59 frameshift, 69 missense, 13 splice site, 12 indels, and 1 large deletion. The missense mutations were distributed across the gene. Cocciadiferro et al. (2018) studied the methylation activity of KMT2D with each of 14 missense mutations, including mutations located in functional N-terminal and C-terminal domains. Nine mutations led to significant impairment of H3K4 monomethylation compared to wildtype, and 2 mutations had borderline effects. In addition, 6 of the mutations led to reduced H3K4me2 and 6 led to reduced H3K4me3.
Daly et al. (2020) identified a de novo heterozygous nonsense mutation in the KMT2D gene (R2099X; 602113.0005) in a patient with KABUK1 who also had holoprosencephaly.
Genotype-Phenotype Correlations
Banka et al. (2012) analyzed the MLL2 gene in a cohort of 116 patients with Kabuki syndrome, including 18 patients previously reported by Hannibal et al. (2011), and identified MLL2 variants in 74 (63.8%). Systematic Kabuki syndrome facial morphology study suggested that nearly all patients with typical Kabuki syndrome facial features have pathogenic MLL2 mutations, although the disorder can be phenotypically variable. In addition, Banka et al. (2012) showed that KABUK1 patients were more likely to have feeding problems, kidney anomalies, early breast bud development, joint dislocations, and palatal malformations in comparison with MLL2 mutation-negative patients. Banka et al. (2012) concluded that the genetic heterogeneity of Kabuki syndrome is not as extensive as previously suggested; however, given the phenotypic variability of the disorder, MLL2 testing should be considered even in atypical patients.
Miyake et al. (2013) screened 81 patients with Kabuki syndrome for mutations in the MLL2 and KDM6A genes and identified MLL2 mutations in 50 (61.7%) and KDM6A mutations in 5 (6.2%). Patients with MLL2 truncating mutations (70%) had facies that were more typical of those seen in the patients originally reported with Kabuki syndrome. High-arched eyebrows, short fifth fingers, and infantile hypotonia were more commonly seen in patients with MLL2 mutations than in those with KDM6A mutations. Only half of the patients with MLL2 mutations had short stature and postnatal growth retardation, compared to all of the patients with KDM6A mutations.
Associations Pending Confirmation
Lo et al. (1998) found an interstitial duplication of the short arm of chromosome 1 with breakpoints involving 1p13.1 and 1p22.1 in a patient with some features suggesting Kabuki syndrome, i.e., mental retardation, small head, eversion of the lateral part of the lower eyelids, epicanthic folds, lateral flare of the eyebrows, short columella, and persistent fetal finger pads. Other chromosome abnormalities described in this disorder, usually as isolated cases, were reviewed.
For discussion of a possible association between Kabuki syndrome and variation in the RAP1A gene on chromosome 1p13, see 179520.
For discussion of a possible association between Kabuki syndrome and variation in the RAP1B gene on chromosome 12q14, see 179530.0001.
Exclusion Studies
Bottani et al. (2006) screened the TGFBR1 (190181) and TGFBR1 (190182) genes in 14 typical Kabuki patients and found no mutations.
In a girl with Kabuki syndrome, Maas et al. (2007) identified a heterozygous de novo 250-kb deletion in the MACROD2 gene (611567) at chromosome 20p12.1. No deletions or pathogenic mutations in the MACROD2 or FLRT3 (604808) genes were identified in 19 additional patients with Kabuki syndrome.
Among 43 Japanese patients with Kabuki syndrome, Kuniba et al. (2008) did not find mutations or deletions in the MACROD2 or FLRT3 genes.
Of 34 patients with Kabuki syndrome, Li et al. (2011) failed to find mutations in the MLL2 gene in 15. Mutation-negative patients were subsequently tested for mutations in 10 functional candidate genes, but no convincing causative mutations could be identified. Li et al. (2011) concluded that MLL2 is the major gene for Kabuki syndrome with a wide spectrum of de novo mutations but that there is further genetic heterogeneity accounting for MLL2 mutation-negative patients.
Several authors, including Hughes and Davies (1994) and Burke and Jones (1995), have recommended that the term 'make-up' be removed from the designation of this syndrome because some families consider the term objectionable.
Adam, M. P., Banka, S., Bjornsson, H. T., Bodamer, O., Chudley, A. E., Harris, J., Kawame, H., Lanpher, B. C., Lindsley, A. W., Merla, G., Miyake, N., Okamoto, N., Stumpel, C. T., Niikawa, N., the Kabuki Syndrome Medical Advisory Board. Kabuki syndrome: international consensus diagnostic criteria. J. Med. Genet. 56: 89-95, 2019. [PubMed: 30514738] [Full Text: https://doi.org/10.1136/jmedgenet-2018-105625]
Adam, M. P., Hudgins, L. Kabuki syndrome: a review. Clin. Genet. 67: 209-219, 2005. [PubMed: 15691356] [Full Text: https://doi.org/10.1111/j.1399-0004.2004.00348.x]
Banka, S., Veeramachaneni, R., Reardon, W., Howard, E., Bunstone, S., Ragge, N., Parker, M. J., Crow, Y. J., Kerr, B., Kingston, H., Metcalfe, K., Chandler, K., and 40 others. How genetically heterogeneous is Kabuki syndrome? MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum. Europ. J. Hum. Genet. 20: 381-388, 2012. [PubMed: 22126750] [Full Text: https://doi.org/10.1038/ejhg.2011.220]
Bottani, A., Pardo, B., Bouchardy, I., Schoumans, J., Toutain, A., Conrad, B. No major contribution of the TGFBR1- and TGFBR2-mediated pathway to Kabuki syndrome. (Letter) Am. J. Med. Genet. 140A: 903-905, 2006. [PubMed: 16528739] [Full Text: https://doi.org/10.1002/ajmg.a.31168]
Burke, L. W., Jones, M. C. Kabuki syndrome: underdiagnosed recognizable pattern in cleft palate patients. Cleft Palate Craniofac. J. 32: 77-84, 1995. [PubMed: 7727492] [Full Text: https://doi.org/10.1597/1545-1569_1995_032_0077_ksurpi_2.3.co_2]
Clarke, L. A., Hall, J. G. Kabuki make-up syndrome in three Caucasian children. (Abstract) Am. J. Hum. Genet. 47 (suppl.): A52, 1990.
Cocciadiferro, D., Augello, B., De Nittis, P., Zhang, J., Mandriani, B., Malerba, N., Squeo, G. M., Romano, A., Piccinni, B., Verri, T., Micale, L., Pasqualucci, L., Merla, G. Dissecting KMT2D missense mutations in Kabuki syndrome patients. Hum. Molec. Genet. 27: 3651-3668, 2018. [PubMed: 30107592] [Full Text: https://doi.org/10.1093/hmg/ddy241]
Courtens, W., Rassart, A., Stene, J.-J., Vamos, E. Further evidence for autosomal dominant inheritance and ectodermal abnormalities in Kabuki syndrome. Am. J. Med. Genet. 93: 244-249, 2000. [PubMed: 10925391] [Full Text: https://doi.org/10.1002/1096-8628(20000731)93:3<244::aid-ajmg17>3.0.co;2-2]
Daly, T., Roberts, A., Yang, E., Mochida, G. H., Bodamer, O. Holoprosencephaly in Kabuki syndrome. Am. J. Med. Genet. 182A: 441-445, 2020. [PubMed: 31846209] [Full Text: https://doi.org/10.1002/ajmg.a.61454]
Digilio, M. C., Marino, B., Toscano, A., Giannotti, A., Dallapiccola, B. Congenital heart defects in Kabuki syndrome. Am. J. Med. Genet. 100: 269-274, 2001. [PubMed: 11343317] [Full Text: https://doi.org/10.1002/ajmg.1265]
Donadio, A., Garavelli, L., Banchini, G., Neri, G. Kabuki syndrome and diaphragmatic defects: a frequent association in non-Asian patients? (Letter) Am. J. Med. Genet. 91: 164-165, 2000. [PubMed: 10748421]
Ewart-Toland, A., Enns, G. M., Cox, V. A., Mohan, G. C., Rosenthal, P., Golabi, M. Severe congenital anomalies requiring transplantation in children with Kabuki syndrome. Am. J. Med. Genet. 80: 362-367, 1998. [PubMed: 9856564]
Franceschini, P., Vardeu, M. P., Guala, A., Franceschini, D., Testa, A., Corrias, A., Chiabotto, P. Lower lip pits and complete idiopathic precocious puberty in a patient with Kabuki make-up (Niikawa-Kuroki) syndrome. Am. J. Med. Genet. 47: 423-425, 1993. [PubMed: 8135293] [Full Text: https://doi.org/10.1002/ajmg.1320470326]
Fryns, J. P., Devriendt, K. Hypoplastic claviculae in the Kabuki (Niikawa-Kuroki) syndrome. (Letter) Genet. Counsel. 9: 57-58, 1998. [PubMed: 9555590]
Galan-Gomez, E., Cardesa-Garcia, J. J., Campo-Sampedro, F. M., Salamanca-Maesso, C., Martinez-Frias, M. L., Frias, J. L. Kabuki make-up (Niikawa-Kuroki) syndrome in five Spanish children. Am. J. Med. Genet. 59: 276-282, 1995. [PubMed: 8599349] [Full Text: https://doi.org/10.1002/ajmg.1320590303]
Genevieve, D., Amiel, J., Viot, G., Le Merrer, M., Sanlaville, D., Urtizberea, A., Gerard, M., Munnich, A., Cormier-Daire, V., Lyonnet, S. Atypical findings in Kabuki syndrome: report of 8 patients in a series of 20 and review of the literature. Am. J. Med. Genet. 129A: 64-68, 2004. [PubMed: 15266618] [Full Text: https://doi.org/10.1002/ajmg.a.30144]
Gillis, R., Klar, A., Gross-Kieselstein, E. The Niikawa-Kuroki (Kabuki make-up) syndrome in a Moslem Arab child. Clin. Genet. 38: 378-381, 1990. [PubMed: 2282718] [Full Text: https://doi.org/10.1111/j.1399-0004.1990.tb03599.x]
Halal, F., Gledhill, R., Dudkiewicz, A. Autosomal dominant inheritance of the Kabuki make-up (Niikawa-Kuroki) syndrome. Am. J. Med. Genet. 33: 376-381, 1989. [PubMed: 2801772] [Full Text: https://doi.org/10.1002/ajmg.1320330317]
Hannibal, M. C., Buckingham, K. J., Ng, S. B., Ming, J. E., Beck, A. E., McMillin, M. J., Gildersleeve, H. I., Bigham, A. W., Tabor, H. K., Mefford, H. C., Cook, J., Yoshiura, K., and 24 others. Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome. Am. J. Med. Genet. 155A: 1511-1516, 2011. [PubMed: 21671394] [Full Text: https://doi.org/10.1002/ajmg.a.34074]
Hinrichs, B., Gramss, B., Meinecke, P. Defective clavicles in Kabuki syndrome. Genet. Counsel. 13: 477-479, 2002. [PubMed: 12558121]
Hoffman, J. D., Ciprero, K. L., Sullivan, K. E., Kaplan, P. B., McDonald-McGinn, D. M., Zackai, E. H., Ming, J. E. Immune abnormalities are a frequent manifestation of Kabuki syndrome. Am. J. Med. Genet. 135A: 278-281, 2005. [PubMed: 15887282] [Full Text: https://doi.org/10.1002/ajmg.a.30722]
Hoffman, J. D., Zhang, Y., Greshock, J., Ciprero, K. L., Emanuel, B. S., Zackai, E. H., Weber, B. L., Ming, J. E. Array based CGH and FISH fail to confirm duplication of 8p22-p23.1 in association with Kabuki syndrome. J. Med. Genet. 42: 49-53, 2005. [PubMed: 15635075] [Full Text: https://doi.org/10.1136/jmg.2004.024372]
Hughes, H. E., Davies, S. J. Coarctation of the aorta in Kabuki syndrome. Arch. Dis. Child. 70: 512-514, 1994. [PubMed: 8048822] [Full Text: https://doi.org/10.1136/adc.70.6.512]
Igawa, H. H., Nishizawa, N., Sugihara, T., Inuyama, Y. Inner ear abnormalities in Kabuki make-up syndrome: report of three cases. Am. J. Med. Genet. 92: 87-89, 2000. [PubMed: 10797429] [Full Text: https://doi.org/10.1002/(sici)1096-8628(20000515)92:2<87::aid-ajmg1>3.0.co;2-g]
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. 56: 127-131, 1995. [PubMed: 7625432] [Full Text: https://doi.org/10.1002/ajmg.1320560202]
Kawame, H., Hannibal, M. C., Hudgins, L., Pagon, R. A. Phenotypic spectrum and management issues in Kabuki syndrome. J. Pediat. 134: 480-485, 1999. [PubMed: 10190924] [Full Text: https://doi.org/10.1016/s0022-3476(99)70207-6]
Kobayashi, O., Sakuragawa, N. Inheritance in Kabuki make-up (Niikawa-Kuroki) syndrome. (Letter) Am. J. Med. Genet. 61: 92-93, 1996. [PubMed: 8741928] [Full Text: https://doi.org/10.1002/ajmg.1320610105]
Kokitsu-Nakata, N. M., Vendramini, S., Guion-Almeida, M. L. Lower lip pits and anorectal anomalies in Kabuki syndrome. Am. J. Med. Genet. 86: 282-284, 1999. [PubMed: 10482881] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19990917)86:3<282::aid-ajmg17>3.0.co;2-q]
Kuniba, H., Tsuda, M., Nakashima, M., Miura, S., Miyake, N., Kondoh, T., Matsumoto, T., Moriuchi, H., Ohashi, H., Kurosawa, K., Tonoki, H., Nagai, T., Okamoto, N., Kato, M., Fukushima, Y., Naritomi, K., Matsumoto, N., Kinoshita, A., Yoshiura, K., Niikawa, N. Lack of C20orf133 and FLRT3 mutations in 43 patients with Kabuki syndrome in Japan. (Letter) J. Med. Genet. 45: 479-480, 2008. [PubMed: 18593871] [Full Text: https://doi.org/10.1136/jmg.2008.058503]
Kuroki, Y., Suzuki, Y., Chiyo, 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. Pediat. 99: 570-573, 1981. [PubMed: 7277097] [Full Text: https://doi.org/10.1016/s0022-3476(81)80256-9]
Kurosawa, K., Kawame, H., Ochiai, Y., Nakashima, M., Tohma, T., Ohashi, H. Patellar dislocation in Kabuki syndrome. Am. J. Med. Genet. 108: 160-163, 2002. [PubMed: 11857567] [Full Text: https://doi.org/10.1002/ajmg.10247]
Lerone, M., Priolo, M., Naselli, A., Vignolo, M., Romeo, G., Silengo, M. C. Ectodermal abnormalities in Kabuki syndrome. Am. J. Med. Genet. 73: 263-266, 1997. [PubMed: 9415681] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19971219)73:3<263::aid-ajmg6>3.0.co;2-t]
Li, M., Zackai, E. H., Niikawa, N., Kaplan, P., Driscoll, D. A. Kabuki syndrome is not caused by a microdeletion in the DiGeorge/velocardiofacial chromosomal region within 22q11.2. Am. J. Med. Genet. 65: 101-103, 1996. [PubMed: 8911598] [Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961016)65:2<101::AID-AJMG3>3.0.CO;2-V]
Li, Y., Bogershausen, N., Alanay, Y., Simsek Kiper, P. O., Plume, N., Keupp, K., Pohl, E., Pawlik, B., Rachwalski, M., Milz, E., Thoenes, M., Albrecht, B., and 11 others. A mutation screen in patients with Kabuki syndrome. Hum. Genet. 130: 715-724, 2011. [PubMed: 21607748] [Full Text: https://doi.org/10.1007/s00439-011-1004-y]
Lo, I. F. M., Cheung, L. Y. K., Ng, A. Y. Y., Lam, S. T. S. Interstitial dup(1p) with findings of Kabuki make-up syndrome. Am. J. Med. Genet. 78: 55-57, 1998. [PubMed: 9637424]
Maas, N. M. C., Van de Putte, T., Melotte, C., Francis, A., Schrander-Stumpel, C. T. R. M., Sanlaville, D., Genevieve, D., Lyonnet, S., Dimitrov, B., Devriendt, K., Fryns, J.-P., Vermeesch, J. R. The C20orf133 gene is disrupted in a patient with Kabuki syndrome. J. Med. Genet. 44: 562-569, 2007. [PubMed: 17586838] [Full Text: https://doi.org/10.1136/jmg.2007.049510]
Makita, Y., Yamada, K., Miyamoto, A., Okuno, A., Niikawa, N. Kabuki make-up syndrome is not caused by microdeletion close to the van der Woude syndrome critical region at 1q32-q41. Am. J. Med. Genet. 86: 285-288, 1999. [PubMed: 10482882] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19990917)86:3<285::aid-ajmg18>3.0.co;2-e]
Matsumura, M., Yamada, R., Kitani, Y., Nishi, T., Yamamoto, H., Oahama, Y., Kuroki, Y. Anorectal anomalies associated with Kabuki make-up syndrome. J. Pediat. Surg. 27: 1600-1602, 1992. [PubMed: 1469590] [Full Text: https://doi.org/10.1016/0022-3468(92)90523-a]
Matsune, K., Shimizu, T., Tohma, T., Asada, Y., Ohashi, H., Maeda, T. Craniofacial and dental characteristics of Kabuki syndrome. Am. J. Med. Genet. 98: 185-190, 2001. [PubMed: 11223856]
McGaughran, J., Aftimos, S., Jefferies, C., Winship, I. Clinical phenotypes of nine cases of Kabuki syndrome from New Zealand. Clin. Dysmorph. 10: 257-262, 2001. [PubMed: 11665999] [Full Text: https://doi.org/10.1097/00019605-200110000-00004]
McGaughran, J. M., Donnai, D., Clayton-Smith, J. Biliary atresia in Kabuki syndrome. (Letter) Am. J. Med. Genet. 91: 157-158, 2000. [PubMed: 10748418]
Micale, L., Augello, B., Maffeo, C., Selicorni, A., Zucchetti, F., Fusco, C., De Nittis, P., Pellico, M. T., Mandriani, B., Fischetto, R., Boccone, L., Silengo, M., and 27 others. Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients. Hum. Mutat. 35: 841-850, 2014. [PubMed: 24633898] [Full Text: https://doi.org/10.1002/humu.22547]
Mihci, E., Tacoy, S., Haspolat, S., Karaali, K. Central nervous system abnormalities in Kabuki (Niikawa-Kuroki) syndrome. (Letter) Am. J. Med. Genet. 111: 448-449, 2002. [PubMed: 12210310] [Full Text: https://doi.org/10.1002/ajmg.10573]
Milunsky, J. M., Huang, X. L. Unmasking Kabuki syndrome: chromosome 8p22-8p23.1 duplication revealed by comparative genomic hybridization and BAC-FISH. Clin. Genet. 64: 509-516, 2003. [PubMed: 14986831] [Full Text: https://doi.org/10.1046/j.1399-0004.2003.00189.x]
Ming, J. E., Russell, K. L., Bason, L., McDonald-McGinn, D. M., Zackai, E. H. Coloboma and other ophthalmologic anomalies in Kabuki syndrome: distinction from CHARGE association. Am. J. Med. Genet. 123A: 249-252, 2003. [PubMed: 14608645] [Full Text: https://doi.org/10.1002/ajmg.a.20277]
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. 128A: 170-172, 2004. [PubMed: 15214010] [Full Text: https://doi.org/10.1002/ajmg.a.30137]
Miyake, N., Koshimizu, E., Okamoto, N., Mizuno, S., Ogata, T., Nagai, T., Kosho, T., Ohashi, H., Kato, M., Sasaki, G., Mabe, H., Watanabe, Y., and 31 others. MLL2 and KDM6A mutations in patients with Kabuki syndrome. Am. J. Med. Genet. 161A: 2234-2243, 2013. [PubMed: 23913813] [Full Text: https://doi.org/10.1002/ajmg.a.36072]
Ng, S. B., Bigham, A. W., Buckingham, K. J., Hannibal, M. C., McMillin, M. J., Gildersleeve, H. I., Beck, A. E., Tabor, H. K., Cooper, G. M., Mefford, H. C., Lee, C., Turner, E. H., and 9 others. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nature Genet. 42: 790-793, 2010. [PubMed: 20711175] [Full Text: https://doi.org/10.1038/ng.646]
Niikawa, N., Kuroki, Y., Kajii, T., Matsuura, N., Ishikiriyama, S., Tonoki, H., Ishikawa, N., Yamada, Y., Fujita, M., Umemoto, H., Iwama, Y., Kondoh, I., and 34 others. Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients. Am. J. Med. Genet. 31: 565-589, 1988. [PubMed: 3067577] [Full Text: https://doi.org/10.1002/ajmg.1320310312]
Niikawa, N., Kuroki, Y., Kajii, T. The dermatoglyphic pattern of the Kabuki make-up syndrome. Clin. Genet. 21: 315-320, 1982. [PubMed: 7116676] [Full Text: https://doi.org/10.1111/j.1399-0004.1982.tb01378.x]
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. Pediat. 99: 565-569, 1981. [PubMed: 7277096] [Full Text: https://doi.org/10.1016/s0022-3476(81)80255-7]
Philip, N., Meinecke, P., David, A., Dean, J., Ayme, S., Clark, R., Gross-Kieselstein, E., Hosenfeld, D., Moncla, A., Muller, D., Porteous, M., Santos, H., Cordeiro, I., Selicorni, A., Silengo, M., Tariverdian, G. Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 16 non-Japanese cases. Clin. Dysmorph. 1: 63-77, 1992. [PubMed: 1285376]
Ruault, V., Corsini, C., Duflos, C., Akouete, S., Georgescu, V., Abaji, M., Alembick, Y., Alix, E., Amiel, J., Amouroux, C., Barat-Houari, M., Baumann, C., and 44 others. Growth charts in Kabuki syndrome 1. Am. J. Med. Genet. 182A: 446-453, 2020. [PubMed: 31876365] [Full Text: https://doi.org/10.1002/ajmg.a.61462]
Selicorni, A., Colombo, C., Bonato, S., Milani, D., Giunta, A. M., Bedeschi, M. F. Biliary atresia and Kabuki syndrome: another case with long-term follow-up. (Letter) Am. J. Med. Genet. 100: 251 only, 2001. [PubMed: 11343312] [Full Text: https://doi.org/10.1002/ajmg.1253]
Shotelersuk, V., Punyashthiti, R., Srivuthana, S., Wacharasindhu, S. Kabuki syndrome: report of six Thai children and further phenotypic and genetic delineation. Am. J. Med. Genet. 110: 384-390, 2002. [PubMed: 12116214] [Full Text: https://doi.org/10.1002/ajmg.10474]
Silengo, M., Lerone, M., Seri, M., Romeo, G. Inheritance of Niikawa-Kuroki (Kabuki makeup) syndrome. (Letter) Am. J. Med. Genet. 66: 368 only, 1996. [PubMed: 8985504] [Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961218)66:3<368::AID-AJMG28>3.0.CO;2-J]
Tsukahara, M., Kuroki, Y., Imaizumi, K., Miyazawa, Y., Matsuo, K. Dominant inheritance of Kabuki make-up syndrome. Am. J. Med. Genet. 73: 19-23, 1997. [PubMed: 9375917]
Turner, C., Lachlan, K., Amerasinghe, N., Hodgkins, P., Maloney, V., Barber, J., Temple, I. K. Kabuki syndrome: new ocular findings but no evidence of 8p22-p23.1 duplications in a clinically defined cohort. Europ. J. Hum. Genet. 13: 716-720, 2005. [PubMed: 15785777] [Full Text: https://doi.org/10.1038/sj.ejhg.5201377]
van Haelst, M. M., Brooks, A. S., Hoogeboom, J., Wessels, M. W., Tibboel, D., de Jongste, J. C., den Hollander, J. C., Bongers-Schokking, J. J., Niermeijer, M. F., Willems, P. J. Unexpected life-threatening complications in Kabuki syndrome. Am. J. Med. Genet. 94: 170-173, 2000. [PubMed: 10982974] [Full Text: https://doi.org/10.1002/1096-8628(20000911)94:2<170::aid-ajmg10>3.0.co;2-2]
Van Laarhoven, P. M., Neitzel, L. R., Quintana, A. M., Geiger, E. A., Zackai, E. H., Clouthier, D. E., Artinger, K. B., Ming, J. E., Shaikh, T. H. Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. Hum. Molec. Genet. 24: 4443-4453, 2015. [PubMed: 25972376] [Full Text: https://doi.org/10.1093/hmg/ddv180]
Wessels, M. W., Brooks, A. S., Hoogeboom, J., Niermeijer, M. F., Willems, P. J. Kabuki syndrome: a review study of three hundred patients. Clin. Dysmorph. 11: 95-102, 2002. [PubMed: 12002156] [Full Text: https://doi.org/10.1097/00019605-200204000-00004]
White, S. M., Thompson, E. M., Kidd, A., Savarirayan, R., Turner, A., Amor, D., Delatycki, M. B., Fahey, M., Baxendale, A., White, S., Haan, E., Gibson, K., Halliday, J. L., Bankier, A. Growth, behavior, and clinical findings in 27 patients with Kabuki (Niikawa-Kuroki) syndrome. Am. J. Med. Genet. 127A: 118-127, 2004. [PubMed: 15108197] [Full Text: https://doi.org/10.1002/ajmg.a.20674]
Wilson, G. N. Thirteen cases of Niikawa-Kuroki syndrome: report and review with emphasis on medical complications and preventive management. Am. J. Med. Genet. 79: 112-120, 1998. [PubMed: 9741469] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19980901)79:2<112::aid-ajmg7>3.0.co;2-s]