Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses.
10.3760/cma.j.cn112140-20220922-00827
- Author:
Dan Dan TAN
1
;
Yi Dan LIU
1
;
Yan Bin FAN
1
;
Cui Jie WEI
1
;
Dan Yang SONG
1
;
Hai Po YANG
1
;
Hong PAN
2
;
Wei Li CUI
3
;
Shan Shan MAO
4
;
Xiang Ping XU
5
;
Xiao Li YU
6
;
Bo CUI
7
;
Hui XIONG
1
Author Information
1. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
2. Department of Central Laboratory, Peking University First Hospital, Beijing 100034, China.
3. Department of Rehabilitation, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450053, China.
4. Department of Neurology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
5. Department of Pediatrics, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
6. Department of Neurology, Tianjin Children's Hospital, Tianjin 300134, China.
7. Department of Rehabilitation Medicine, Third Affiliated Hospital of Zhengzhou University, Henan Maternal and Child Health Care Hospital, Zhengzhou 450052, China.
- Publication Type:Journal Article
- MeSH:
Humans;
Abnormalities, Multiple;
Retrospective Studies;
Intellectual Disability/genetics*;
Bone Diseases, Developmental/complications*;
Tooth Abnormalities/complications*;
Facies;
Muscular Dystrophy, Duchenne/complications*;
Muscular Atrophy, Spinal/complications*;
Carrier Proteins;
Nuclear Proteins
- From:
Chinese Journal of Pediatrics
2023;61(4):345-350
- CountryChina
- Language:Chinese
-
Abstract:
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.
