Kabuki syndrome

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Classification according to ICD-10
Q89.8 Other specified congenital malformations
ICD-10 online (WHO version 2019)

The Kabuki syndrome (formerly also Niikawa-Kuroki syndrome or Kabuki make-up syndrome called) is a very rare congenital disorder resulting from a genetic defect. The name is derived from Kabuki , a traditional Japanese form of theater, as the affected patients have special facial features that are reminiscent of the eye make-up used there . However, the addition "make-up" was removed from the name as it was objected to by affected families.

Comparison of Kabuki Theater Makeup with Typical Kabuki Syndrome Facial Features
A child with Kabuki syndrome who has the “scrunchy face”

description

The symptoms of Kabuki syndrome can vary greatly; most of the people affected have conspicuous facial features, a congenital intellectual disability and several organic malformations .

The peculiarities of the face are long eyelid slits that hang down in the outer third, long eyelashes, curved eyebrows, protruding auricles, a flat and wide nose and drawn-down corners of the mouth. The mental handicap usually leads to a slight to moderate decrease in intelligence. Congenital heart defects , such as coarctation of the aorta or an atrio-ventricular septal defect , are present in around 50% of patients. Unspecific anomalies in skeletal structure are also very common. These include clinodactyly (bending of a phalanx in the hand skeleton), scoliosis (lateral bending of the spine) and dislocations of the hip or kneecap . Neurological symptoms such as muscle hypotension , seizures, microcephaly , visual disturbances caused by nystagmus or strabismus can be observed in about 2/3 of the affected patients. Over 50% of patients experience hearing impairment during their lifetime. Some teeth are often missing in both the primary and permanent dentition.

The syndrome in itself does not reduce the life expectancy of those affected, but the resulting malformations can lead to it.

Incidence

The incidence is around 1: 32,000, regardless of gender, origin, or environment. In Japan, it was diagnosed in about 100 children by 2005. In contrast, 300 patients were listed in one study.

genetics

Most of the cases described in the literature are sporadic de novo mutations . However, there are also known familial cases that an autosomal - dominant inheritance suggest. So far, two genes are known which lead to Kabuki syndrome in the event of a defect: KMT2D and KDM6A . KMT2D (previously known as MLL2, MLL4 or ALR) was identified as the cause of Kabuki syndrome type 1 in 2010, and mutations in KDM6A were identified as the cause of Kabuki syndrome type 2 two years later.

diagnosis

In 2019, a clinical diagnosis guide was published by a team of experts. Accordingly, the diagnosis can be made at any age if there is a history of infantile hypotension, developmental retardation, and / or intellectual disability and either or both of the following main criteria: (1) a pathogenic or likely pathogenic mutation in KMT2D or KDM6A; (2) typical dysmorphic features such as: long cleft eyelids with drooping of the outer third of the lower eyelid and two or more of the following secondary criteria: (1) arched and wide eyebrows with frayed lateral third, (2) wide and flat tip of the nose, (3) large , prominent or protruding ears, and (4) persistent fetal finger pads.

therapy

There is no cure for Kabuki syndrome; treatment is symptomatic. If a new diagnosis is made, in most cases the heart function (echocardiography) and kidney function (ultrasound) are examined, the immunoglobulin level is determined, and vision and hearing tests are carried out. In the case of, for example, seizures, standard epilepsy drugs are given. The CRISPR / Cas9 technology is currently being tested (February 2019 to March 2020) at the University Hospital in Montpellier on 4 Kabuki patients . On the one hand, this is intended to research the syndrome, but therapeutic approaches are also planned.

Initial description

The kabuki syndrome was first described in 1981 by the Japanese doctors Norio Niikawa ( 新 川 詔 夫 ) and Yoshikazu Kuroki ( 黒 木 良 和 ). The Kabuki syndrome is therefore also called Niikawa-Kuroki syndrome .

  • Children with Kabuki Syndrome
  • Child with Kabuki Syndrome 06.jpg
  • Child with Kabuki Syndrome 03.jpg
  • Child with Kabuki Syndrome 9.jpg

literature

Review article

  • MW Wessels et al: Kabuki syndrome: a review study of three hundred patients. In: Clin Dysmorphol 11, 2002, pp. 95-102, PMID 12002156 .
  • N. Niikawa et al .: Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients. In: Am J Med Genet 31, 1988, pp. 565-589, PMID 3067577 .
  • MP Adam, L. Hudgins: Kabuki syndrome: a review. In: Clin Genet 67, 2005, pp. 209-219, PMID 15691356 .
  • D. Geneviève et al .: Atypical findings in Kabuki syndrome: report of 8 patients in a series of 20 and review of the literature. In: Am J Med Genet A 129A, 2004, pp. 64-68, PMID 15266618 .

Technical article

  • GE Utine et al: Kabuki syndrome and trisomy 10p. In: Genet Couns 19, 2008, pp. 291-300, PMID 18990985
  • G. Spano et al: Oral features in Kabuki make-up syndrome. In: Eur J Pediatr Dent 9, 2008, pp. 149-152, PMID 18844445
  • L. Rodríguez et al .: A small and active ring X chromosome in a female with features of Kabuki syndrome. In: Am J Med Genet A 146A, 2008, pp. 2816-2821, PMID 18925662 .
  • H. Kuniba et al: Lack of C20orf133 and FLRT3 mutations in 43 patients with Kabuki syndrome in Japan. In: J Med Genet 45, 2008, pp. 479-480, PMID 18593871 .
  • JM Milunsky et al: A re-examination of the chromosome 8p22-8p23.1 region in Kabuki syndrome. In: Clin Genet 73, 2008, pp. 502-503, PMID 18336587 .
  • NM Maas et al .: The C20orf133 gene is disrupted in a patient with Kabuki syndrome. In: J Med Genet 44, 2007, pp. 562-569, PMID 17586838 .
  • KW Kimberley et al: BAC-FISH refutes report of an 8p22-8p23.1 inversion or duplication in 8 patients with Kabuki syndrome. In: BMC Med Genet 7, 2006, p. 46, PMID 16709256 .

Web links

Commons : Kabuki Syndrome  - Collection of Pictures, Videos, and Audio Files

Individual evidence

  1. ↑ Sarah B. Ng et al .: Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome . In: Nature genetics . tape 42 , no. 9 , 2010, ISSN  1061-4036 , p. 790-793 , doi : 10.1038 / ng.646 , PMID 20711175 , PMC 2930028 (free full text).
  2. ^ HE Hughes, SJ Davies: Coarctation of the aorta in Kabuki syndrome . In: Archives of Disease in Childhood . tape 70 , no. 6 , 1994, ISSN  1468-2044 , pp. 512-514 , doi : 10.1136 / adc.70.6.512 , PMID 8048822 , PMC 1029872 (free full text).
  3. ↑ LW Burke, MC Jones: Kabuki syndrome: underdiagnosed recognizable pattern in cleft palate patients . In: The Cleft Palate-Craniofacial Journal: Official Publication of the American Cleft Palate-Craniofacial Association . tape 32 , no. 1 , 1995, ISSN  1055-6656 , pp. 77-84 , doi : 10.1597 / 1545-1569_1995_032_0077_ksurpi_2.3.co_2 , PMID 7727492 .
  4. ↑ N. Bögershausen, B. Wollnik: Unmasking Kabuki Syndrome . in: Clinical Genetics Volume 83, 2013, pp. 201-211. doi : 10.1111 / cge.12051
  5. ↑ a b orpha.net: Kabuki syndrome. accessed on December 31, 2008.
  6. ↑ N. Niikawa et al .: Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients . In: American Journal of Medical Genetics . tape 31 , no. 3 , 1988, ISSN  0148-7299 , pp. 565-589 , doi : 10.1002 / ajmg.1320310312 , PMID 3067577 .
  7. ^ Margaret P Adam: National Organization for Rare Disorders: Kabuki Syndrome .
  8. ↑ S. Fisch: first description of a rare syndrome. ( Memento of the original from April 26, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. In: Ärztewoche 42, 2005. @1@ 2Template: Webachiv / IABot / www.springermedizin.at
  9. Jump up ↑ Marja W. Wessels, Alice S. Brooks, Jeannette Hoogeboom, Martinus F. Niermeijer, Patrick J. Willems: Kabuki syndrome: a review study of three hundred patients . In: Clinical Dysmorphology . tape 11 , no. 2 , 2002, ISSN  0962-8827 , p. 95-102 , PMID 12002156 .
  10. ↑ Chong Kun Cheon, Young Bae Son, Jung Min Ko, Yeoun Joo Lee, Ji Sun Song, Jea Woo Moon, Bo Kyoung Yang, Il Soo Ha, Eun Jung Bae, Hyun-Seok Jin, Seon-Yong Jeong: Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome . In: Journal of Human Genetics . tape 59 , no. 6 , 2014, ISSN  1435-232X , p. 321-325 , doi : 10.1038 / year 2014.25 , PMID 24739679 .
  11. ↑ Sarah B. Ng et al .: Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome . In: Nature genetics . tape 42 , no. 9 , 2010, ISSN  1061-4036 , p. 790-793 , doi : 10.1038 / ng.646 , PMID 20711175 , PMC 2930028 (free full text).
  12. ↑ Damien Lederer et al .: Deletion of KDM6A, a Histone Demethylase Interacting with MLL2, in Three Patients with Kabuki Syndrome . In: The American Journal of Human Genetics . tape 90 , no. 1 , 2012, ISSN  0002-9297 , p. 119-124 , doi : 10.1016 / j.ajhg.2011.11.021 , PMID 22197486 .
  13. ^ Margaret P Adam et al .: Kabuki syndrome: international consensus diagnostic criteria. Journal of Medical Genetics. February 2019; 56 (2) 89-95 0: 1-7. DOI: 10.1136 / jmedgenet-2018-105625
  14. ↑ Margaret P Adam, L Hudnins, M Hannibal: Kabuki Syndrome Gene Reviews [Internet] PMID 21882399
  15. ^ University Hospital, Montpellier: Exploiting Epigenome Editing in Kabuki Syndrome: a New Route Towards Gene Therapy for Rare Genetic Disorders (Epi.KAB) . https://ClinicalTrials.gov Identifier NCT03855631
  16. ↑ N. Niikawa et al .: Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency . In: The Journal of Pediatrics . tape 99 , no. 4 , 1981, ISSN  0022-3476 , pp. 565-569 , doi : 10.1016 / s0022-3476 (81) 80255-7 , PMID 7277096 .
  17. ↑ Y. Kuroki et al .: A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation . In: The Journal of Pediatrics . tape 99 , no. 4 , 1981, ISSN  0022-3476 , pp. 570-573 , doi : 10.1016 / s0022-3476 (81) 80256-9 , PMID 7277097 .