Clinical phenotype and genetic analysis of intellectual developmental disorder with seizures and language delay due to 12q24.31 deletion
10.3760/cma.j.cn113694-20240207-00085
- VernacularTitle:12q24.31缺失所致智力发育障碍伴癫痫发作和语言迟缓患儿临床表型及遗传学分析
- Author:
Yi LI
1
;
Ruofei LIAN
;
Gongao WU
;
Daoqi MEI
;
Shichao ZHAO
;
Yan DONG
Author Information
1. 郑州大学第三附属医院儿童神经内科，郑州 450052
- Keywords:
Epilepsy;
Seizures;
Language development disorders;
Intellectual developmental disabilities;
12q24.31 deletion;
SETD1B gene
- From:
Chinese Journal of Neurology
2024;57(9):975-983
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical and genetic features of children with intellectual developmental disorder with seizures and language delay (IDDSELD) due to 12q24.31 deletion and SETD1B locus variants. Methods:The clinical data of a child with 12q24.31 deletion diagnosed in the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in September 2022 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) and copy number variations sequencing (CNV-seq) were used for genetic analysis. The relevant literatures were reviewed to summarize the clinical features of the disease.Results:The proband was a 7 years and 9 month old girl who had clinical features of global developmental delay, epilepsy, hyperactivity, hypertonia, gait disorder, special facial features (high eyebrow arch, big ears, upper lip protrusion), funnel chest, lumbar lordosis. Karyotypic analysis showed 46XX in the proband. CNV-seq showed 12q24.31 (chr12: 121895654-122449092) position had a deletion of about 553.44 kb which contained the SETD1B gene. Trio-WES showed deletion of all exons 1-16 of the SETD1B gene. CNV-seq results of her parents were normal: the SETD1B gene was wild-type. This type has not been reported in China. Four children with IDDSELD caused by 12q24.31 deletion (including the SETD1B gene) were retrieved (totally 5 cases including this case), with male to female ratio of 1∶4, all with de novo mutations, and all with mental retardation, cephalo-facial and skeletal malformations. Three cases had seizures, 2 cases still had developmental backwardness after treatment, and 1 case was seizure controlled. Forty-seven cases of IDDSELD due to point mutation in the SETD1B gene were retrieved: male to female ratio was 31∶16, missense mutations (38/47) were predominant, most were de novo mutations (36/47), and a few were inherited from their fathers/mothers (6/47) or of unknown origin (5/47), with clinical manifestations of speech delay (43/47), growth retardation (43/47), intellectual disability (37/41), behavioral problems (37/47), facial malformations (34/47), skeletal malformations (23/47), obesity (16/47), skin abnormalities (11/47), etc. Thirty-nine cases were combined with seizures, 23 of whom were under control after treatment, and 8 cases were recorded as still having developmental backwardness after treatment. Conclusions:IDDSELD patients are rare at home and abroad, with diverse clinical phenotypes and difficult diagnosis. Symptomatic treatment is the main approach. And the patients can leave behind seizures and varying degrees of developmental backwardness. Among them, patients with 12q24.31 deletion are relatively rare and have not been reported in China, and this type is more common in females, all of whom have de novo mutations, and genetic testing is helpful for the early diagnosis of IDDSELD.
