MRI of a family with leukoencephalypathy with vanishing white matter

Leukoencephalopathy with vanishing white matter (VWM) is a newly described entity with characteristic MRI features. We report the cranial MRI findings in three sisters with slowly progressive neurological deterioration. The MRI showed symmetrical diffuse abnormalities of cerebral white matter with hypointensity on FLAIR images. The diagnosis of leukoencephalopathy with VWM was made on the basis of genetic analysis.     

白质消融性白质脑病2 例报告并文献复习

目的探讨白质消融性白质脑病(VWM)的临床表现及基因表型。方法回顾性分析经基因检测确诊的2例VWM患儿的临床资料,并复习相关文献。结果 2例患儿发病年龄分别为8个月、2岁,既往精神运动发育均正常;在急性发热后出现精神反应差,认知、运动功能进行性倒退;脑脊液检查未见异常;头颅磁共振提示两侧大脑半球脑白质对称性异常信号;基因检测1例为EIF2B5复合杂合变异;另1例EIF2B2复合杂合变异,其中c.911_913del缺失变异导致第305号氨基酸缺失(p.305del),属于新突变,短期内死亡。结论 VWM早期精神、运动发育基本正常,发热后出现进行性神经系统功能倒退,预后差。EIF2B突变可确诊。     

An unusual neuroimaging finding and response to immunotherapy in a child with genetically confirmed vanishing white matter disease

Background

We present an unusual neuroimaging finding in a young girl with genetically confirmed vanishing white matter disease and a possible response to immunotherapy.

全外显子组序列分析新生儿FGFR2基因相关疾病1例

目的通过对1例新生儿期特殊面容、神经系统结构畸形患儿进行全外显子组序列检测分析,旨在为该患儿寻找潜在的致病原因。方法纳入1例在复旦大学附属儿科医院(我院)新生儿病房住院期间未能明确诊断的多发畸形患儿,主要临床表型为前额突出、腭弓高、耳位低、枕部较平,双侧脑室扩大、透明隔部分缺如、胼胝体发育异常,采用Sure Selct Human All Exon捕获试剂盒和Illumina Hi Seq2000测序平台,行全外显子组序列检测。数据分析采用复旦大学附属儿科医院转化中心所建立的高通量测序数据分析流程。采用Sanger测序进行验证。结果患儿全外显子组序列检测数据,共检测到79 064个变异,经过质量控制筛选、变异频率筛选、变异分类筛选,剩余645个变异。在进一步分析中,645个变异中有159个其所在基因在OMIM数据库及HGMD数据库与疾病相关。从3个已经报道的突变位点中锁定致病突变为FGFR2基因(NM_000141)c.C1040G,p.S347C。Sanger测序在家系内验证该位点为新发(de novo)突变。结论采用全外显子组序列检测,明确诊断FGFR2相关疾病1例。并且结合我院已经建立的高通量测序数据分析和临床诊断流程,为新生儿多发畸形寻找潜在的致病基因提供了快速、高效的方法。     

A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder

Background

Early-onset epileptic encephalopathy (EOEE) is a severe convulsive disorder with a poor developmental prognosis. Although it has been associated with mutations in a number of genes, the fact that there is a large proportion of patients who remain undiagnosed suggests that there are many more still-unknown genetic causes of EOEE. Achieving a genetic diagnosis is important for understanding the biological basis of the disease, with its implications for treatment and family planning.

Atypical presentation of multisystem disorders in two girls with mitochondrial DNA deletions

We describe two girls with atypical presentations of multisystem disorders due to deletions in mitochondrial DNA (mtDNA). One presented with painful carpopedal spasms due to hypoparathyroidism at the age of 4 years. The disease was rapidly progressive with development of truncal and limb ataxia, spastic paraparesis, muscle weakness and wasting, pigmentary retinal degeneration and sensorineural hearing loss. She had short stature and vitiligo patches, hirsutism, anaemia, diabetes mellitus and exocrine pancreatic dysfunction. The other girl presented at the age of 6 years with polydipsia, polyuria and fatigue due to renal tubular dysfunction. The disease was insidiously progressive with poor growth and development of sensorineural hearing loss, muscle weakness and truncal and limb ataxia. Morphological, enzyme histochemical and biochemical investigations indicated mitochondrial dysfunction of skeletal muscle, liver and kidney in one patient and of skeletal muscle and liver in the other. Both patients had large proportions of mtDNA molecules with deletion in liver, kidney, skeletal muscle and blood cells.Conclusion It may be concluded that symptoms from several different organs may be the first manifestation of a mtDNA deletion disorder.     

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??Abstract??Objective The purpose of this study was to use diffusion tensor imaging to investigate the status of cerebral white matter??WM?? maturation in the first 2 years after birth. Methods A total of 67 children ranging in age from birth to 24 months underwent conventional MRI and diffusion tensor imaging with gradient encoding in fifteen directions?? all on a 1.5T MRI system. All children were divided into six groups according to month. Fractional anisotropy was measured in five deep WM structures ??posterior limb of internal capsule?? anterior limb of internal capsule?? genu and splenium of corpus callosum?? optic radiation?? and four peripheral WM regions??associational WM underlying prefrontal?? occipital cortex?? temporal lobe and centrum semiovale??. Results In the same months of age?? different parts of the white matter FA values were significantly different??the deep white matter FA values were higher than the shallow??in birth-to-28 days baby?? corpus callosum FA values was the highest in deep white matter ??followed by the corpus callosumknee?? posterior limb of internal capsule?? optic radiation and limb of internal capsule??in the shallow white matter??centrum semiovale was the highest?? followed by the temporal lobe?? frontal lobe and occipital subcortical white matter. With increasing month-old?? white matter FA values of the various parts gradually increased??showing positive correlation. In the same parts of the white matter??FA values change in different rate for different ages??which was a statistically significant ??P??0.05??. Conclusion Combination of T1WI and T2WI and diffusion tensor imaging can be used for quantitative evaluation of cerebral white matter development of children in the first 2 years after birth..     

托莫西汀在注意力缺陷多动障碍患儿中的精准药学研究：CYP2D6基因检测和治疗药物监测

约3%的孕妇患有慢性肾脏病（chronic kidney disease,CKD）。该文复习了关于CKD母亲（包括透析和肾移植患者）的新生儿结局的文献。文献显示：妊娠合并CKD会增加新生儿发生早产、低出生体重及小于胎龄儿的风险,但不增加发生先天结构畸形的风险;从远期结局来看,对子代体格发育、免疫功能无显著影响;子代的神经发育结局与早产、低出生体重相关,与宫内药物暴露无关。仍需更进一步的研究及随访以探讨CKD母亲的新生儿结局。