Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses
Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively...
| Veröffentlicht in: | Zhonghua er ke za zhi = Chinese journal of pediatrics. - 1960. - 61(2023), 4 vom: 02. Apr., Seite 345-350 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | Chinese |
| Veröffentlicht: |
2023
|
| Zugriff auf das übergeordnete Werk: | Zhonghua er ke za zhi = Chinese journal of pediatrics |
| Schlagworte: | English Abstract Journal Article IRF2BPL protein, human Carrier Proteins Nuclear Proteins |
| Zusammenfassung: | Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis |
|---|---|
| Beschreibung: | Date Completed 05.04.2023 Date Revised 05.04.2023 published: Print Citation Status MEDLINE |
| ISSN: | 0578-1310 |
| DOI: | 10.3760/cma.j.cn112140-20220922-00827 |