Clinical and genetic study of rare cases with coexistence of dual genetic diagnoses

Objective The clinical and genetic characteristics of patients with dual genetic diagnoses (DGD) were analyzed in order to improve precise diagnosis and treatment. Methods Clinical and genetic data of patients with DGD from January 2021 to February 2022 were collected and analyzed. Results Among 10 children, 7 were boys and 3 were girls. The last visit/follow-up ages were 2.0 to 8.4 years old. Cases 1-5, all boys, showed myopathic gait, poor running and jumping, and significantly increased levels of serum creatine kinase. Pathogenic variations in DMD gene were confirmed by genetic testing, and they were diagnosed with Duchenne muscular dystrophy. At the same time, the 5 patients also had a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy type 1, fragile X syndrome, Phelmn-McDerimid syndrome and cerebral cavernous malformations type 3. Multiple epiphyseal dysplasia type 6, and neurofibromatosis type 1 were identified in case 6. Bethlem myopathy, and osteogenesis imperfecta type XV were identified in case 7. Turner syndrome and Segawa syndrome were found in case 8. Chromosome 22q11.2 microduplication syndrome caused by a 2.64 Mb microduplication, and autosomal dominant lower extremity-predominant spinal muscular atrophy-1 caused by pathogenic variation in DYNC1H1 gene were confirmed in case 9. KBG syndrome due to pathogenic variation in ANKRD11 gene, and neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy caused by pathogenic variation in IRF2BPL gene were identified in case 10. Conclusion: This study provides important information and basis for the diagnosis of patients with coexistence of double genetic diseases.