A Child Of Xp21 Contiguous Gene Deletion Syndrome:Clinical Analysis And Literature Review

Objective We reviewed the clinical data of a case of Xp21 contiguous gene deletion syndrome and summarized the clinical characteristics and diagnosis ideas of this type of disease,in order to improve clinicians’ understanding of the disease.And we can select accurate genetic testing to confirm the diagnosis to reduce the rate of missed diagnosis and misdiagnosis,and further genetic counseling can be done to reduce the risk of recurrence of rare diseases.Methods1.1 subjects:During 2017-2019,one patient with Xp21 contiguous gene deletion syndrome admitted to the Affiliated Hospital of Qingdao University was selected.1.2 methods:(1)We retrospectively summarized and analyzed the patient’s clinical data,laboratory examinations,imaging results and screening of blood and urine metabolism.(2)After obtaining the consent of the medical ethics committee of the hospital,we contacted with his family members.After signing the informed consent form,the peripheral bloods of the child and family members were collected for gene sequencing.The detection methods were whole exon gene detection and chromosome CNV detection.We searched for pathogenic genes consistent with clinical manifestations.(3)According to the clinical characteristics of patients and the results of genetic testing,we searched the literature in the Wanfang database,China Knowledge Network database(CNKI)and Biomedicine Literature database(Pubmed)with “complex glycerol kinase deficiency,NROB1,DMD,GK,IL1RAPL1,Xp21” as keywords,and we compared the relevant clinical characteristics with the characteristics of the patient,and summarized and reviewed the literature.Results(1)The child was a boy of 1 year and 3 months old.He presented with feeding difficulties,developmental delay,mental retardation,repeated vomiting,repeated infections,repeated convulsions,hyponatremia,hypertriglyceridemia,hypertransaminaseemia,gallstones,myocardial damage and encephalitis.Repeated laboratory tests revealed that alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatine kinase(CK),creatine kinase MB(CK-MB),triglyceride(TG)and adrenocorticotropic hormone(ACTH)levels were significantly increased.And blood sodium and cortisol were reduced.Brain MRI showed abnormal signal shadows of bilateral fronto-parietal-occipital-temporal lobes and suggested encephalitis.Genetic metabolism of blood and urine showed increased glycerol in urine and lack of glycerol kinase.(2)No significant positive mutation was found in the whole exon gene test of the patient and his families.The result of chromosome CNV detection showed a 8.84 Mb deletion of the X chromosome,ranging from p21.3 to p21.1.Deletion fragment involved forty-four genes,and it included four morbid genes which were IL1RAPL1,GK,NROB1 and DMD.He was diagnosed with Xp21 contiguous gene deletion syndrome.Due to personal and economic reasons,the families of the child did not undergo chromosome CNV testing and verification.(3)We retrieved related literature through Pub Med,Wanfang and CNKI databases,and reviewed the literature.The clinical manifestations of the syndrome are determined by the size,nature and genes involved in the missing fragments.The clinical manifestations are multiple single gene syndrome.The most common combination include Adrenal Hypoplasia Congenital(AHC)caused by the deletion of NROB1 gene,Glycerol Kinase Deficiency(GKD)caused by the deletion of(GK)gene and Duchenne Muscular Dystrophy(DMD)caused by the deletion of DMD gene.Genetic testing is required to perform to confirm the missing genes,and the diagnosis should be confirmed in combination with clinical symptoms and auxiliary examinations.At present,there is no effective treatment for this disease.The main treatment is symptomatic and supportive treatment.The prognosis of this disease is extremely poor and most of them die.The disease is relatively rare,and domestic doctors are not well aware of it,which leads to delays in diagnosis are common.Conclusions1.The diagnosis of contiguous gene deletion syndrome requires comprehensive consideration.We need to follow the principle of "monism".Then search the relevant literature,and select the relevant genetic testing technology to confirm the diagnosis.So,we can reduce the rate of missed diagnosis and misdiagnosis.2.Carry out genetic counseling and prenatal diagnosis to reduce morbidity of rare diseases.