A case report of Kabuki syndrome with infantile spasm and literature review / 解放军医学杂志

Objective Through literature review to retrospectively study the clinical characteristics, treatment and prognosis of Kabuki syndrome with infantile spasm. Methods The clinical data of a case of Kabuki syndrome with infantile spasm hospitalized at the first medical center of Chinese PLA General Hospital in August 2019 were retrospectively analyzed, search on PubMed, CNKI, Wanfang Medical Online and online Mendelian Inheritance in Man (OMIM), to summarize the clinical data of Kabuki syndrome with infantile spasm and to explore its relationship with genotypes. Results A boy, 1 year and 7 months old, was admitted for "growth lag, intermittent convulsions for more than 1 year and 1 month". His growth and development were generally backward, had microcephaly, short stature and spasms, magnetic resonance imaging of brain showed normal, the thyroid hormone and growth hormone levels were normal, genetic analysis revealed a denovo frameshift mutation in KDM6A gene (c.2170-c.2171 delAT, p.I724Ifs∗5), electroencephagram showed hypsarrhuthmia, with a series of convulsions, diagnosed as "infantile spasm; Kabuki syndrome", after treating with ACTH, the spasms was completely controlled, multiple reexamination of EEG significantly improved. A total of 16 English literatures and 1 Chinese literature were obtained. There were 48 children had been diagnosed as Kabuki syndrome with epilepsy, including 6 children as Kabuki syndrome and infantile spasm. Among the above 6 cases, only 2 genetic test results were reported, 1 was missense mutation of KMT2D gene (c.96c >G, p.apsp32glu), and 1 was frameshift mutation of KDM6A gene (c.2515_2518del, p.apsn839valfs). Conclusion The new frameshift mutation of KDM6A gene (c.2170-c.2171delAT) in this child could lead to infantile spasm of Kabuki syndrome. Kabuki syndrome could be associated with infantile spasms. If spasm occurs and accompanied by a special face, Kabuki syndrome needs to be considered, gene sequencing should be performed if necessary, early treatment can completely control infantile spasms in all children with Kabuki syndrome, the abnormal of EEG could back to normal, will have a favorable prognosis.

Diagnosis and treatment of Kabuki syndrome and its recent progress in molecular mechanisms / 国际儿科学杂志

Kabuki syndrome(KS),also called kabuki make-up syndrome,is characterized by backward growth retardation,skeletal developmental delay,major facial dysmorphic features,multi-organ abnormalities and abnormal dermatoglyphic pattern and mild or moderate mental retardation.For the molecular genetic pathogenesis of KS,KTM2D and KDM6A gene mutations have been identified as pathogenic genes of KS,which regulate the gene expression through chromatin remodelling and histone modification.At present,the etiology and pathogenesis of KS are still unknown.There is no useful biochemical index and standard radiographic findings for the diagnosis of KS.Molecular genetic diagnosis is still to be explored.Currently,the diagnosis of KS is mainly based on five cardinal manifestations:a peculiar face,skeletal anomalies,dermatoglyphic abnormalities,mild to moderate mental retardation and postnatal growth deficiency.For these patients,it can reach a better prognosis the by clinical early detection,early diagnosis,early intervention,as well as improving the growth level,symptomatic treatment,active prevention and treatment of complications as far as possible.

Síndrome de Kabuki: presentación de un Caso y Revisión de la Literatura / Kabuki Syndrome: A case report and literature review

Resumen El síndrome de Kabuki (SK) es una patología muy rara, descrita por primera vez en 1981 por Niikawa y Kuroki en Japón. Se han publicado cerca de 400 casos a nivel mundial. En Colombia se conocen cinco casos diagnosticados y publicados; el caso objeto de este estudio sería el sexto en nuestro país. Presentamos la descripción del caso de una paciente de 2 años y 6 meses con rasgos dismórficos compatibles con síndrome de Kabuki. Examen físico: fisuras palpebrales elongadas, eversión del tercio lateral párpado inferior, cejas arqueadas con tercio lateral más despoblado, puente nasal deprimido, boca en carpa, paladar hendido, pabellones auriculares de baja implantación con rotación posterior. El síndrome de Kabuki se caracteriza por sus anomalías faciales peculiares que se consideran son la única manifestación que puede orientar al diagnóstico del mismo sin excepciones. Recientemente se han identificado mutaciones sin sentido y de corrimiento del marco de lectura, entre otras en el gen MLL2 en aproximadamente el 75 % de los casos y en una menor proporción deleciones y mutaciones sin sentido en el gen KDM6A.

Abstract Kabuki syndrome is a rare disease described by Kuroki and Niikawa in Japanese population in 1981. There are over 400 cases over the world and 5 cases described in Colombian population. Therefore this is the 6th Kabuki syndrome found in Colombia. We report a 2 years old female with Kabuki syndrome phenotype. Clinical examination showed: long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, left palate and low setup ears. Kabuki syndrome includes facial features whit specific characteristics enough to classify the patients. However, there are some mutations in MLL2 gene present in almost 75 % of Kabuki syndrome. In addition there are some deletion and duplications abnormalities in KMD6A gene described in Kabuki syndrome patients.

Kabuki syndrome: clinical and molecular characteristics / 소아과

Kabuki syndrome (KS) is a rare syndrome characterized by multiple congenital anomalies and mental retardation. Other characteristics include a peculiar facial gestalt, short stature, skeletal and visceral abnormalities, cardiac anomalies, and immunological defects. Whole exome sequencing has uncovered the genetic basis of KS. Prior to 2013, there was no molecular genetic information about KS in Korean patients. More recently, direct Sanger sequencing and exome sequencing revealed KMT2D variants in 11 Korean patients and a KDM6A variant in one Korean patient. The high detection rate of KMT2D and KDM6A mutations (92.3%) is expected owing to the strict criteria used to establish a clinical diagnosis. Increased awareness and understanding of KS among clinicians is important for diagnosis and management of KS and for primary care of KS patients. Because mutation detection rates rely on the accuracy of the clinical diagnosis and the inclusion or exclusion of atypical cases, recognition of KS will facilitate the identification of novel mutations. A brief review of KS is provided, highlighting the clinical and genetic characteristics of patients with KS.