A Study On The Phenotypes And Genotypes Of Kabuki Syndrome And A Literature Review

Objectives To analyze the clinical and genetic characteristics of 8 patients with Kabuki syndrome(KS).Methods The clinical data of 8 patients with KS were collected.Blood samples were taken for whole-exome sequencing(WES)for 8 patients and their parents if available.Combining with previously published Chinese KS patients,the phenotypic and genotypic spectra of 55 KS Chinese patients were summarized and compared with those in other countries(n=86).In addition,two patients were treated with recombined human growth hormone(rh GH).Result(1)Genetic sequencing identified 7 KMT2 D variants(c.3926 del C,c.5845 del C,c.6595 del T,c.12630 del G,c.11472＿11473del,c.16294C>T,and c.16442 del G)and one KDM6 A variant(c.2668-2671del).Of them,3 variants(c.5845 del C,c.11472＿11473del and c.12630 del G)in KMT2 D gene and the variant(c.2668-2671del)in KDM6 A gene were de novo.(2)The clinical characteristics of 8 patients were as following: facial dysmorphism(n=8),intellectual disability(n=7),cardiac abnormalities(n=6),short stature(n=5),skeletal abnormalities(n=3),hearing impairment(n=3),hypoglocemia(n=2),breast development(n=2),hypotonia(n=1),fingerpads(n=1),white matter myelination delay(n=1)and thin pituitary(n=1).(3)With the previously patients added,18 of 55 Chinese patients had brain CT/MRI imaging.Of them,only 27.8%(5/18)patients had brain abnormalities,such as white matter myelination delay,cerebellar vermis dysplasia,corpus callosum hypoplasia,thin pituitary,hydrocephalus and Dandy-Walker malformation.In addition,The Chinese KS patients presented with typical clinical phenotypes including facial dysmorphism,intellectual disability,growth retardation,fifth finger clinodactyly,fingertip pads and cardiac abnormalities,as previously reported in non-Chinese patients,but of variable features prevalence.(4)Patient 7 and 8 received rh GH therapy for 12 months and 6 months,respectively.The height of patient 7 increased by 9cm(+1.47SD),whereas that of patient 8increased by 3.5cm(+0.19SD).Conclusions(1)In this report,four novel variants(c.3926 del C,c.5845 del C,c.12630 del G,c.11472＿11473del and c.16442 del G)in KMT2 D gene and one KDM6 A c.2668-2671 del variant are described.(2)About 27.8% patients presented with brain abnormalities,which is the first report on the characteristics of brain CT or MRI imaging in Chinese patients.Some brain abnormalities including white matter myelination delay and thin pituitary that are not previously reported.(3)KS patient with short stature might benefit from rh GH treatment.