Genetic analysis of undiagnosed ataxia-telangiectasia-like disorders

Objectives

Defects in DNA damage responses or repair mechanisms cause numerous rare inherited diseases, referred to as “DNA-repair defects” or “DNA damage deficiency”, characterized by neurodegeneration, immunodeficiency, and/or cancer predisposition. Early accurate diagnosis is important for informing appropriate clinical management; however, diagnosis is frequently challenging and can be delayed, due to phenotypic heterogeneity. Comprehensive genomic analysis could overcome this disadvantage. The objectives of this study were to determine the prevalence of ataxia-telangiectasia (A-T) and A-T-like DNA-repair defects in Japan and to determine the utility of comprehensive genetic testing of presumptively diagnosed patients in facilitating early diagnosis.

妊娠寨卡病毒感染对胎儿脑/神经系统发育的影响

近年来,南美洲寨卡病毒（Zika virus）流行,同时该地区吉兰-巴雷综合征（Guillain-Barré syndrome）、新生儿小头畸形发病率明显升高。截至2016年3月,疫情共波及美洲33个国家和地区,超过19万人疑似感染。另外,欧洲、亚洲诸国也均有输入性病例的报道。妊娠寨卡病毒感染与胎儿神经系统发育异常存在着高度的相关性,这已引起了全球范围的密切关注。寨卡病毒影响胎儿神经系统发育的机制可分为直接和间接两条途径：①寨卡病毒可通过血-胎盘屏障,且病毒具有嗜神经性,直接影响胎儿的神经系统发育;②寨卡病毒通过其他介质间接影响胎儿的神经系统发育,如通过胎儿炎症反应介质或免疫交叉反应产生的抗体等。虽然具体机制目前尚未完全明确,但现阶段及时阐明妊娠寨卡病毒感染对胎儿神经系统发育的影响及防控该病毒在中国境内的传播,将具有极为重要的临床意义和长远的社会意义。     

24 Mb deletion of 6q22.1-->q23.2 in an infant with pulmonary atresia, ventricular septal defect, microcephaly, developmental delay and facial dysmorphism

24 Mb deletion of 6q22.1→q23.2 in an infant with pulmonary atresia, ventricular septal defect, microcephaly, developmental delay and facial dysmorphism.     

A 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication in a boy with extreme microcephaly with simplified gyral pattern, vermis hypoplasia and corpus callosum agenesis

We here report a boy presenting with developmental delay, growth retardation, facial dysmorphisms, vermis hypoplasia, micropolygyria and corpus callosum agenesis. Conventional and high resolution cytogenetic analyses were normal but high resolution oligonucleotide array-CGH, performed at the age of 4 years, allowed the characterisation of a de novo 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication. Numerous 1qter deletions have already been described associated with brain malformations. Among 1q44 deleted genes, AKT3 is the strongest candidate gene for vermis hypoplasia and corpus callosum agenesis.     

Neuropathology of Seckel syndrome in fetal stage with evidence of intrauterine developmental retardation

Summary Marked intrauterine developmental retardation in a fetal case of Seckel syndrome was morphologically defined in the 29th week of gestation by comparing with a large number of length-matched and age-matched controls. Telencephalic micrencephaly with reduced neuroblast production, retarded functional differentiation of the pituitary gland, and generalized hypotrophy with craniofacial stigmata were observed.     

Cockayne's syndrome

Summary The clinical and necropsy findings have been described in an 11 year old girl with classical Cockayne's syndrome which consists of microcephaly, dwarfism, bird facies, mental deficiency, retinal pigmentation, deafness, large hands and feet, and a thick skull with a small pituitary fossa. The disease, as is usual, appeared after a normal first year of life and was characterized by initial mental and physical retardation followed by progressive deterioration. The most striking neuropathological findings were marked atrophy of white matter, patchy demyelination of residual fibres in cerebrum, cerebellum, brain stem and spinal cord, fine deposition of calcium in the cerebral and cerebellar cortical ribbon and coarse focal calcification of the basal ganglia. The most likely cause of this rare condition is probably an inherited genetic defect involving several germ layers.

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Zusammenfassung Klinisch-autoptischer Fallbericht eines 11 jährigen Mädchens mit klasischem Cockayne-Syndrom, bestehend aus Mikrocephalie, Zwergwuchs, Vogelgesicht, psychischer Retardierung, Retinitis pigmentosa, Taubheit, großen Händen und Füßen sowie dickem Schädel mit kleiner Fossa hypophyseos. Wie üblich, setzte die Erkrankung nach regelrechter Frühentwicklung ein. Sie war durch initiale psychische und physische Retardierung mit späterer progressiver Demenz gekennzeichnet. Die wesentlichen neuropathologischen Befunde waren deutliche Atrophie des Markes, fleckige Entmarkung der verbliebenen Fasern in Groß- und Kleinhirn, Hirnstamm und Rückenmark, zarte Kalkablagerungen im Rindenband des Groß- und Kleinhirns sowie grobe fokale Verkalkungen in den Stammganglien. Die wahrscheinlichste Ursache dieser seltenen Erkrankung ist ein angeborener genetischer Defekt, der verschiedene Keimblätter betrifft.

     

头针加穴位注射对小头畸形儿童智力的影响

目的 观察头针加穴位注射对小头畸形儿童智商的影响。方法 以头针为主配合穴位注射治疗小头畸形儿童25例，治疗前后采用中国．韦氏智力量表对患儿进行智力测定。结果与结论 针刺能提高小头畸形儿童智商水平，特别对言语智商有明显的影响。