Genotype and Clinical Phenotype Analysis of a Family of Kennedy Disease

Abstract Objective: By analyzing the clinical phenotype, genotype and family characteristics of a Kennedy disease family, to explore the clinical and genetic characteristics of the family, and to further improve the understanding of the disease. And through the analysis of genotype and clinical phenotype to draw a pedigree diagram, provide genetic counseling, in order to block the continued inheritance of disease-causing genes. Methods: The research subjects were from a family of Kennedy disease discovered in January 2019. For 5 clinically diagnosed patients including the proband, the Kennedy's disease function rating scale (KD1234) and the spinal cord and bulbar muscular atrophy rating scale (SBMAFRS) were used to assess their condition, and their clinical phenotypes, laboratory tests, and neurological Analysis of electrophysiological results. After the patient's informed consent was obtained, 5ml of venous blood was drawn from the 3 members of the proband, and the CAG repeat sequence of the first exon of the androgen receptor (AR) gene was checked by polymerase chain reaction (PCR), and genetic testing was performed. analysis. Results: 1) Clinical features: The average age of onset of 5 clinical diagnosis members was (30.8±2.85) years, and the average course of disease was (12.3±4.93) years at the age of onset to milestones. This family has gynecomastia as the first symptom, and it is the most significant clinical feature. The lesions mainly involve the medulla oblongata and spinal cord. The testosterone level of 5 cases was in the normal range, and the progesterone was increased. 3 cases of estradiol were slightly elevated. The serum creatine kinase (CK) was significantly increased in 5 cases. Electromyography showed chronic extensive neurogenic damage, abnormal sensory and motor conduction. 2) The results of genetic testing showed that the 3 clinically diagnosed cases underwent genetic testing for 48 CAG repetitions (≥35 times are abnormal), and genetic diagnosis was confirmed, indicating stable inheritance. Conclusion: 1) Gynecomastia is the first symptom of the family. Androgen resistance symptoms are the outstanding clinical manifestations of this family, in addition to gynecomastia, including testicular atrophy, infertility, sexual dysfunction, etc.; 2) Changes in serum creatine kinase may indicate the progress or relief of symptoms; 3) This family There is chronic extensive neurogenic damage, prominent with sensory nerve involvement; 4) Rehabilitation training may delay the progression of muscle wasting symptoms; 5) There is a stable inheritance of CAG repeats in this family; 6) Genetic testing can diagnose the disease , The genotype is consistent with the clinical phenotype; 7) The pedigree diagram drawn according to the clinical phenotype and genotype can be used as an important basis for genetic counseling.