A phenotypic and genetic study on β-propeller protein-associated neurodegeneration / 中华儿科杂志

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.

The clinical and radiological features of children with first attack of inflammatory demyelinating central nervous system disorders and seropositivity to myelin-oligodendrocyte glycoprotein / 中华神经科杂志

Objective To investigate the clinical and radiological features of children with first attack of inflammatory central nervous system disorders and seropositivity to myelin-oligodendrocyte glycoprotein (MOG).Methods The clinical course,cerebrospinal fluid (CSF),MRI studies,MOG status and outcomes were retrospectively analyzed in children with first attack of inflammatory central nervous system disorders and seropositivity to MOG who were hospitalized in Children's Hospital of Fudan University from January 2016 to April 2017.Results Thirteen patients including 8 males and 5 females were included in this study,the ratio of male/female was 1.6∶ 1,and the median age was six years.Ten patients were diagnosed with acute disseminating encephalomyelitis,and three with clinically isolated syndromes.Seven patients had elevated CSF lymphocyte cells,and five patients had elevated CSF protein.All the patients' sera were tested for the anti-MOG IgG,which ranged from 1∶10 to 1∶100 with cell-based assay.MRI results showed that multiple anatomical areas were involved.Twelve patients had brain lesions,in which 10 patients had multiple lobes involved and four had tumefactive demyelinating lesions.The affected anatomical areas included white matters in 11 cases,thalamus/basal ganglias in nine,corpus callosums in three,brainstems in 10,spinal cord in five.The MRI features were characterized by hazy,bilateral lesions without clear boundaries.Clinical symptoms were fully restored in all the patients after treated with intravenous globulin and methyl prednisone.The average follow-up time was 8.9 months,and none of the patients had clinical recurrence.Conclusions MOG was associated with many kinds of inflammatory demyelinating diseases of central nervous system in children.Most of them were diagnosed with acute disseminating encephalomyelitis which has an acute or sub acute clinical course.The clinical manifestations of patients showed diversity.Multiple anatomical areas were involved,and treatment with intravenous globulin and methyl prednisone was effective in the acute phase.All of the patients had a favorable outcome.

Novel compound heterozygous TBC1D24 mutations in a boy with infantile focal myoclonic epilepsy and literature review / 中华儿科杂志

Objective@#To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutations.@*Method@#The clinical data of a patient with novel TBC1D24 compound heterozygous mutations from Children′s Hospital of Fudan University were collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to April 2016) by using search terms "TBC1D24" "epilepsy" . The clinical features, electroencephalogram (EEG) and prognosis of the patients with TBC1D24 gene mutations were studied.@*Result@#The patient was a boy with non-consanguineous healthy parents.He had an acute episode of focal continuous myoclonus lasting a few hours with consciousness preserved at the age of 3 months.Myoclonic jerks alternatively affected the eyelids, either the right or left limbs, sometimes triggered by fever or fatigue.The frequency was once 3-7 days.At the age of 6 months he was found to have myoclonus seizures with onset from a unilateral eyes lid and limb lasting 10 more minutes and subsequently affected four extremities or the trunk.They occurred once 3-4 months with perserved consciousness and lasted from several hours to up to ten more hours.They mostly disappeared during sleep.He had ataxia and mild mental retarding.Paroxysmal anomalies were not found on ictal traces.A novel compound heterozygous mutation of TBC1D24 gene, c. 730G>A, p.A244T and c. 1571G>C, p.R524P were found in the patient.Further study showed that c. 730G>A mutation was inherited from his father and c. 1571G>C from his mother. These two were not reported in public databases and predicted deleterious by Mutation Taster and polyphen-2.Literature relevant to TBC1D24 published all around the world was reviewed, no Chinese cases with TBC1D24 gene mutations had been reported. The total of 24 cases including the present case with TBC1D24 gene mutation were reported.Among them, 11 cases had compound heterozygous mutations and 13 cases had homozygous mutations.Ten mutations were identified, including 1 termination mutation, 1 frameshift mutation and 8 missense mutations.@*Conclusion@#TBC1D24 gene mutational analysis should be performed on patients with early-onset focal continuous myoclonus, if the etiology was unclear.

Poorly-differentiated chordoma with INI1 loss: a clinicopathologic study / 中华病理学杂志

Objective@#To analyze the clinicopathologic characteristics of poorly-differentiated chordoma with INI1 loss in children and to discuss the differential diagnosis.@*Methods@#The clinical, radiological, histopathological profiles and molecular pathologic characteristics of two pediatric poorly differentiated chordoma cases with INI1 loss were reviewed.@*Results@#The patients were a girl and a boy. Both lesions involved the slope. Both patients were presented with progressive muscle weakness or neck pain. Radiological examination showed clivus bone destruction and compression of the brain stem and cervical spinal cord. Histologically, the tumor cells lacked typical organization and were associated with inflammatory cells infiltration. On high power field, the tumor cells were ovoid or fusiform with prominent atypia, vacuolated nuclei and prominent nucleoli. By immunohistochemistry, the tumor cells expressed cytokeratin, epithelial membrane antigen, brachyury and were negative for INI1. In both cases, INI1 gene deletion was detected by FISH.@*Conclusions@#Poorly-differentiated chordoma with INI1 loss mainly occurs in children. The morphology is different from classical chordoma.INI1 gene deletion is detectable by FISH. It can be distinguished from atypical teratoid/rhabdoid tumors and other neoplasms by the identification of nuclear brachyury expression. The loss of INI1 expression in poorly-differentiated chordoma might be associated with a poorly-differentiated morphology and an adverse prognosis.