TY - JOUR
T1 - Expansion of the genotypic and phenotypic spectrum of CTCF-related disorder guides clinical management
T2 - 43 new subjects and a comprehensive literature review
AU - Valverde de Morales, Hannah Gabriela
AU - Wang, Hsiao Lin V.
AU - Garber, Kathryn
AU - Cheng, Xiaodong
AU - Corces, Victor G.
AU - Li, Hong
N1 - Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2023/3
Y1 - 2023/3
N2 - Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with CRD included intellectual disability/developmental delay (91%) with speech delay (65%), motor delay (53%), feeding difficulties/failure to thrive (66%), ocular abnormalities (56%), musculoskeletal anomalies (53%), and behavioral problems (52%). Other congenital anomalies were also reported, but none of them were common. Our findings expanded the genotypic and phenotypic spectrum of CRD that will guide genetic counseling, management, and surveillance care for patients with CRD. Additionally, a newly built facial gestalt on the Face2Gene tool will facilitate prompt recognition of CRD by physicians and shorten a patient's diagnostic odyssey.
AB - Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with CRD included intellectual disability/developmental delay (91%) with speech delay (65%), motor delay (53%), feeding difficulties/failure to thrive (66%), ocular abnormalities (56%), musculoskeletal anomalies (53%), and behavioral problems (52%). Other congenital anomalies were also reported, but none of them were common. Our findings expanded the genotypic and phenotypic spectrum of CRD that will guide genetic counseling, management, and surveillance care for patients with CRD. Additionally, a newly built facial gestalt on the Face2Gene tool will facilitate prompt recognition of CRD by physicians and shorten a patient's diagnostic odyssey.
KW - CTCF
KW - facial gestalt
KW - gene
KW - genotype
KW - phenotype
KW - variant
UR - http://www.scopus.com/inward/record.url?scp=85143884815&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85143884815&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.63065
DO - 10.1002/ajmg.a.63065
M3 - Article
C2 - 36454652
AN - SCOPUS:85143884815
SN - 1552-4825
VL - 191
SP - 718
EP - 729
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 3
ER -