Novel KDM6A mutation in a Chinese infant with Kabuki syndrome: A case report

BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There are few case reports and genetic analyses,especially of KDM6A gene mutation,in China.CASE SUMMARY This study reports a de novo KDM6A mutation in a Chinese infant with KS.A 2-month-old Chinese baby was diagnosed with KS,which manifested as hypoglycemia,congenital anal atresia at birth,feeding difficulties,hypotonia,and serious postnatal growth retardation.He died of recurrent respiratory infections at age 13 mo.DNA sequencing of his blood DNA revealed a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19).CONCLUSION We present a Chinese KS patient with a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19),broadening the mutation spectrum.

Fetal Phenotype and Prenatal Diagnosis of Kabuki Syndrome

Kabuki syndrome(MIM 147920)is an autosomal dominant rare disease featured with multiple malformations and mental retardation.The main clinical manifestations of Kabuki syndrome are characteristic facial features,skeletal abnormalities,dermatoglyphic abnormalities,postpartum growth retardation,mild to moderate mental retardation,as well as other structural and functional abnormalities that may involve multiple systems.The establishment of diagnosis needs to be combined with clinical phenotype and the discovery of pathogenic mutation.Compared with the abundant descriptions and records of genotype-phenotype of postpartum patients,few prenatal diagnosis cases of Kabuki syndrome had been reported,which partially result from lacking the knowledge of its phenotype in fetuses that might suggest the diagnosis.This report performed comprehensive prenatal examinations to identify a fetus's etiology with multiple structural anomalies characterized by ascites,thickening of local skin,and cardiac abnormalities.We ruled out intrauterine infection,thalassemia,and chromosome abnormality by corresponding tests.Finally,trio whole-exome sequencing revealed a de novo heterozygous variation c.15641g>A(p.r5214h)in exon 48 of the KMT2D gene was the fetus's genetic pathogeny causing Kabuki syndrome.This result suggests that Kabuki syndrome should be in the suspected etiology list for prenatal hydrops/ascites.Our study confirmed that prenatal whole-exome sequencing is an efficient tool for diagnosing fetal abnormalities,and a multidisciplinary team is necessary for providing pregnancy guidance to patients.

A case report:Hearing disorder in Kabuki make-up (Niikawa-Kuroki) syndrome in China

The study reports a case of a 5-year-old Chinese girl diagnosed with Kabuki make-up Syndrome(KMS).The patient showed classic KMS appearance:widely separated eyes,ectropion of lateral one-third lower eyelids,flat nasal tip,and prominent ears.Auditory features in this individual included bilateral severe sensorineural hearing loss and lack of 40 Hz AERP responses identified at I year of age.The individual received cochlear implant(CI) in the left ear when 5 years old.and rehabilitation after CI treatment were 3 in speech intelligibility and 5 in auditory performance.Thus,our findings suggest that cochlear implant may be helpful to restore hearing for individuals with Kabuki syndrome.

Kabuki-Syndrome and Congenital Heart Disease-A Twenty-Year Institutional Experience

Background:Patients with genetic syndromes who undergo surgery to correct congenital heart defects can be at risk for increased morbidity or mortality.Surgical outcomes and postoperative courses following congenital heart surgery in patients with Kabuki-Syndrome(KS)have not been well studied.Objectives:The purpose of this study was to describe the postoperative courses and associated outcomes in the largest set of KS patients undergoing congenital heart surgery to date.Methods:Patients with a confirmed molecular diagnosis of KS and a diagnosis of a CHD admitted to Texas Children’s Hospital between January 1,2000 and January 1,2020 were included(n=20).Demographics and medical histories were collected from the hospitals’electronic health records.Results:Of 20 patients identified with KS and a CHD,15 required surgical correction of their congenital cardiac malformation.Median age and weight at the time of surgery was 2 months and 4.1 kg,respectively.Median duration of hospital stay was 49 days for all surgeries and 151 days for the Norwood procedure.Postoperative infections and pleural effusions were detected and treated in 45.8%and 50%of patients,respectively.There was no in-hospital mortality for any surgery.Median follow up time was 5.6 years;survival at 6 years was 94%.Conclusions:Although KS patients seem to be at increased risk for a more complicated,prolonged postoperative course than that of patients without a genetic syndrome,patients with a diagnosis of a CHD and KS do not appear to be at increased risk of mortality following congenital heart surgery.

Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome

Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases.In this study,a Chinese woman,presenting with characteristic facial features of KS,came for pre-pregnancy consultation.We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling.Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants,respectively.The candidate variant was verified by Sanger sequencing.We identified a novel de novo KDM6A pathogenic variant(c.3521G>A)in the woman,which was in line with the Face2Gene analysis result.Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A.Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.