A phenotypic and genetic study on β-propeller protein-associated neurodegeneration
10.3760/cma.j.issn.0578-1310.2019.11.004
- VernacularTitle: 儿童β螺旋蛋白相关性神经变性的基因型和表型特点
- Author:
Wenhui LI
1
;
Qian CHEN
2
;
Hua WANG
3
;
Yuanfeng ZHANG
4
;
Ying YANG
5
;
Aijie LIU
5
;
Wanting LIU
2
;
Xinna JI
2
;
Ziteng TENG
3
;
Yucai CHEN
4
;
Bingbing WU
6
;
Haowei YANG
7
;
Yi WANG
1
;
Yuehua ZHANG
5
;
Shuizhen ZHOU
1
Author Information
1. Department of Neurology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
2. Department of Neurology, Capital Institute of Pediatrics, Beijing 100020, China
3. Department of Pediatrics, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China
4. Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
5. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
6. Shanghai Key Lab of Birth Defects, Pediatrics Research Institute, Children′s Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
7. Department of Radiology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Neurodegenerative diseases;
Genes, WDR45;
Neuroimaging
- From:
Chinese Journal of Pediatrics
2019;57(11):830-836
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical and genetic features of β-propeller protein-associated neurodegeneration (BPAN).
Methods:The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children’s Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed.
Results:Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures)were found on ictal electroencephalogram(EEG) recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age) . All patients had de novo variations in WDR45(6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977-1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C).
Conclusions:The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.
