Pedigree analysis of Xp21 contiguous gene deletion syndrome and literature review / 中华实用儿科临床杂志

ABSTRACT

Objective:To explore the clinical and genetic features of Xp21 contiguous gene deletion syndrome, in order to improve clinicians′ understanding of the disease.Methods:The clinical manifestations, diagnosis and treatment process as well as genetic characteristics of 3 brothers from 1 family with Xp21 contiguous gene deletion syndrome were studied.Literatures were retrieved with key words including " Xp21 contiguous gene deletion syndrome" and " complex glycerol kinase deficiency" in CNKI, VIP database, Wanfang database, Biomedicine Literature database (PubMed) and Web of Science from the database establishment to December 2019, and the relevant features were reviewed.Results:The surviving proband was a boy, the fourth child and the fourth birth.He was suspected as congenital adrenal hyperplasia(salt-losing type) because of significant hyperpigmentation and obviously increased plasma adrenocorticotropic hormone (ACTH)in the neonatal period.Serum triglyceride and creatine phosphokinase were elevated, and urine analysis revealed massive glyceroluriam in this patient.But his serum 17-hydroxyprogesterone was normal.5.16 Mbp deletion in Xp21.3p21.1 was detected by single nucleotide polymorphisms, and the diagnosis of Xp21 contiguous gene deletion syndrome was confirmed.After the supplements of hydrocortisone and fludrocortisone, pigmentation was improved, and the serum ACTH became normal.Now, the patient was 3 years and 8 months old, having pseudomuscle hypertrophy, intellectual and language developmental delay, but no the electrolyte disorder.His parents and 18-years-old sister were healthy.While his two elder brothers who were suspected as cerebral palsy and muscular atrophy due to the symptoms of dark skin color and psychomotor development delay after birth died at the age of 1 year and 1.5 years, respectively.Deletions in Xp21.3p21.1 region were found in his mother and elder sister.A total of 22 cases with full and complete clinical data and definite genetic diagnosis were collected from domestic and foreign literature, and 13 cases of them had the onset during the neonatal period.The main symptoms were congenital adrenal insufficiency, muscular dystrophy, hypertriglyceridemia, developmental retardation in most cases, and special facial features in a few cases.Besides, these patients had large fragment deletion in Xp21 region and the major deleted genes included NR0B1, GK and DMD genes, etc. Conclusions:Xp21 contiguous gene deletion syndrome has a complex clinical phenotype and is easy to be misdiagnosed, it can lead to adrenal insufficiency and poor prognosis in the neonatal period.It is necessary to make differential diagnosis by serum biochemical and genetic analysis.