关键词: Beckwith-Wiedemann综合征, CDKN1C基因, 舌大

Abstract: Objective To investigate the clinical characteristics, genetic characteristics and diagnosis of a child with CDKN1C gene related Beckwith-Wiedemann syndrome. Methods A patient with Beckwith-Wiedemann syndrome born on December 4, 2021 in the obstetrics department of Zhongshan People's Hospital in Guangdong Province was selected as the study object. Clinical data were collected for retrospective analysis, peripheral venous blood of the children and their parents were collected for family whole exome sequencing, and the research progress of Beckwith-Wiedemann syndrome was reviewed. Results The patient, a female, was 34 weeks +2 preterm infant. The main clinical manifestations were large tongue after birth, hypoglycemia during hospitalization, and umbilical hernia during late follow-up. The genetic test results indicated that the C. 235T > C (P.RP79ARg) carried by the patient was missense variation in the coding region of CDKN1C gene. The T→C conversion occurred at nucleotide 235 of CDKN1C gene, that is, the missense mutation occurred at amino acid 79, resulting in the mutation of tryptophan to arginine, and neither of the parents carried the mutation gene. According to the American Society for Medical Genetics and Genomics (ACMG) Guidelines and recommendations from the Clinical Genome Data Center (ClinGen), this variant is defined as a causative variant that may affect outcomes such as polydactyly, genital abnormalities, nipple valvs, and cleft palate. After discharge, regular follow-up was conducted to monitor the body weight and head circumference at 1 month of age below the 10th percentile of the same age and gender, and the body weight, length and head circumference at 3, 6, 8, 12 and 24 months of age were all at the 10-90th percentile of the same age and gender. Physical examination at 6:00 on January 6 revealed umbilical hernia 1*1*0.5cm, frontal hemangioma, and retinopathy. At 22 days old in August, physical examination found that the great movement was lagging behind, and the great movement ability was significantly improved during the later follow-up, and no abnormalities were found. Between 1 year 4 months and 1 year 5 months, there are repeated respiratory infections, and even severe pneumonia. During the follow-up, there were no abnormalities in language development, no feeding difficulties, and no tumor growth was found up to 24 months of age. Conclusion Combined with the clinical characteristics and genetic testing results, the patient was diagnosed as Beckwith-Wiedemann. The heterozygous missense variation of CDKN1C gene C.235T > C (P.RP79arg) may be the genetic cause of the patient. The main manifestations were omphalocele, huge tongue and excess growth on one side of the body. Other clinical manifestations were transient hypoglycemia, bright red nevus on the face, visceral hypertrophy and tumor. BWS is considered a clinical spectrum in which affected individuals may have many or only one or two typical clinical features. Post-natal physical examination is particularly important for early diagnosis and treatment of the disease. The purpose of this case report and related genetic research progress is to improve the understanding of clinical diagnosis and treatment of Beckwith-Wiedemann syndrome and to avoid misdiagnosis and missed diagnosis.

Key words: Beckwith-Wiedemann syndrome, CDKN1C gene, Hyperglossia