ɫ��ʧ��֢15���ٴ��о�

目的总结色素失禁症患儿临床特征,特别是皮肤、神经系统、眼部、基因改变的特点,提高对该病的认识。方法对1994~2004年首都儿科研究所附属儿童医院收治的色素失禁症患儿15例进行临床多方面检查分析,并进行追踪随访,其中7例患儿接受基因检测。结果15例患儿均有皮肤受累;神经系统受累10例:10例中发生癫5例,其中合并脑积水2例,均死亡,表现有智力发育落后6例;眼部受累6例:视神经萎缩2例,先天白内障1例,视网膜发育不良1例,斜视2例;接受基因检测的7例中5例的NEMO基因的共有序列NEMOΔ4~10缺失。结论色素失禁症患儿皮肤改变显著,眼部及神经系统病变严重,应得到早期诊断治疗。     

Hypomelanosis of Ito with cerebral malformation

Syndromic forms of cortical maldevelopment continue to be a curiosity. Hypomelanosis of Ito (HI) is the presence of whirled hypochromic skin lesions often associated with nondermatological manifestations. The polymorphism of brain abnormalities associated with HI is well known. We report three cases of Hypomelanosis of Ito, occuring in infants, and associated with cerebral malformation.     

Male cases of incontinentia pigmenti: Case report and review

Male patients with Bloch-Sulzberger incontinentia pigmenti (IP type II) are rare and more severely affected than their female counterparts, with a significant occurrence of sex chromosome aneuploidy. This document introduces a new male IP type II patient and reviews 48 males reported with IP. Twenty-eight of the 49 patients meet current criteria for diagnosis of IP type II. The phenotype is variable and the incidence of documented developmental delay is 25%. Five patients had Klinefelter syndrome (47,XXY). Most patients were reported prior to 1961 when chromosome analysis was not available. Biopsy and laboratory reports considered to be “consistent with” the diagnosis of IP were seen in patients meeting criteria as well as those who would not currently be given the diagnosis. The histologic findings considered diagnostic are varied. This variability may be accounted for by differences in stage of disease, biopsy site, histologic technique, and reporting style. Conversely, this may indicate that the diagnostic weight given to the biopsy should be reconsidered. Eosinophilia was not a consistent finding. Overall, differences in reporting, ascertainment, and length of follow-up lead to difficulty in interpreting or predicting the natural history of males with IP type II. Based on the existing literature, they appear to have a higher rate of mental retardation than the general population, but there does not appear to be a correlation between severity of physical and mental involvement. The presence of sex chromosome aneuploidy documented in the more recent cases emphasizes the need for chromosome analysis in any male patient suspected of IP type II. Am. J. Med. Genet. 77:201–218, 1998. © 1998 Wiley-Liss, Inc.     

Incontinentia pigmenti revisited. A novel nonsense mutation of the IKBKG gene

Aim: To describe and evaluate the clinical and molecular findings of patients with incontinentia pigmenti (IP) in Greece. Methods: We examined 12 female patients, initially aged 2 weeks to 7 months with clinical diagnosis of IP. Standard tests were performed including skin biopsies and ocular, dental and neurologic examinations. Molecular analysis was carried out on 8 out of 12 cases. Results: The initial clinical examination was stage 1 (vesicular lesions), stage 2 (verrucous lesions) or stage 3 (hyperpigmented linear lesions of the trunk/limbs). At the final clinical examination, 10 of our patients had typical vesicular, verrucous or mixed hyper‐hypopigmented skin lesions which had persisted from the neonatal period; seven had delayed dentition or conical teeth; two had developmental delay; one had microcephaly and strabismus and two had scarring alopecia. In seven patients, deletion of exons 4–10 of the IKBKG gene was found. In one patient, skewed X‐inactivation was demonstrated and a novel mutation p.Gln332X was found. The mothers’ DNA analyses were all normal. Conclusion: In our sample, all the cases were sporadic and the diagnosis of IP was based mainly on clinical features and confirmed with skin histology. Molecular analysis was used to find the mutations, in some cases to confirm diagnosis and to identify the carriers, which are crucial for prenatal and preimplantation diagnosis.     

Transpupillary thermotherapy (TTT) for age-related macular degeneration

Purpose. To review the results of transpupillary thermotherapy (TTT) on choroidal neovascular membranes associated with age-related macular degeneration (AMD). Materials and Methods. 35 eyes of 35 patients with AMD and choroidal neovascularization and exudation were treated with TTT and had fundus photographs and fluorescein angiography (FA) before and at least six months after TTT. 28 eyes had predominantly occult lesions as seen on FA, while 7 demonstrated primarily classic lesions. All were treated with 650 mw power or less using the 810 nm diode laser (3000 micron spot, duration of 60 seconds). Visual acuity, lesion size, and amount of subretinal fluid were determined by results of examination and review of photographs and fluorescein angiograms. Results. A 50% reduction in subretinal fluid was achieved in 67% of treated eyes overall, with stabilization of vision (less than three lines of visual acuity lost) in 86%. Complications from treatment were infrequent (9%) and involved hemorrhage noted in the region of treatment upon follow-up. Conclusion. TTT promotes resolution of subretinal fluid and appears to stabilize visual acuity in patients with exudative AMD.     

NF-kappaB and inflammation in genetic disease

By responding to pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, and controlling itself the expression of numerous mediators of inflammation, NF-kappaB plays a pivotal role in controlling the proper sequence of events characterizing the inflammation process. Although excessive NF-kappaB activation is often associated with inflammatory signs in many different tissues, impaired NF-kappaB activation can also generate inflammation. This is the case in humans suffering from the genetic disease incontinentia pigmenti that exhibit severe skin inflammation. Identifying the molecular basis of this pathology, mutations affecting the gene coding for NEMO, has allowed production of mouse models for investigating the disease. Their characterization supports the view that a very tight positive and negative regulation of the NF-kappaB signaling pathway is required in vivo to ensure not only a fine-tuned response to injury or infection but also to maintain tissue homeostasis.     

Therapy resistant neonatal seizures, linear vesicular rash, and unusually early neuroradiological changes: incontinentia pigmenti

CASE PRESENTATION: A substance abusing G2P1 mother spontaneously delivered at term an appropriate for gestational age girl. Neonatal seizures appeared at 21 hours and empiric anticonvulsive and antimicrobial treatment was started. At 25 hours, first vesicles appeared. While routine evaluations remained normal, a head CT revealed multifocal ischemic injuries, and a later MRI showed multifocal petechiae and diffusion abnormalities in the corticospinal tracts. The clinical diagnosis of incontinentia pigmenti (stage 1) was secured by histopathology. Follow-up at 13 months showed global developmental delay. DISCUSSION: We discuss the unusually early bilateral, fronto-occipital corticomedullar ischemias (CT day 3). On the MR imaging (day 7) extensive symmetric cerebral corticomedullar destruction and diffusion sequences with corticospinal tracts abnormalities are seen, which then evolve (day 26) to extensive symmetric cerebral destruction. We review the literature, genetics, suspected pathophysiology and possible neonatal manifestation. CONCLUSION: Incontinentia pigmenti is rare and, therefore, diagnosis is frequently delayed. Nevertheless, in the setting of therapy refractory seizures, excluded infections, and linear vesicular rash, a high index of suspicion is needed. This is the first report of simultaneous corticomedullar involvement as early as the third day of life.     

Ocular manifestations in the X-linked intellectual disability syndromes

Intellectual disability (ID), a common neurodevelopmental disorder characterized by limitations of both intellectual functioning and adaptive behavior, affects an estimated 1–2% of children. Genetic causes of ID are often accompanied by recognizable syndromal patterns. The vision apparatus is a sensory extension of the brain, and individuals with intellectual disabilities frequently have coexisting abnormalities of ocular structures and the visual pathway system. About one-third of the X-linked intellectual disability (XLID) syndromes have significant eye or ocular adnexa abnormalities that provide important diagnostic clues. Some XLID syndromes (e.g. Aicardi, cerebrooculogenital, Graham anophthalmia, Lenz, Lowe, MIDAS) are widely known for their characteristic ocular manifestations. Nystagmus, optic atrophy, and strabismus are among the more common, nonspecific, ocular manifestations that contribute to neuro-ophthalmological morbidity. Common dysmorphic oculofacial findings include anophthalmia, microphthalmia, hypertelorism, and abnormalities in the configuration or orientation of the palpebral fissures. Four XLID syndromes with major ocular manifestations (incontinentia pigmenti, Goltz, MIDAS, and Aicardi syndromes) are notable because of male lethality and expression occurring predominantly in females. The majority of the genes associated with XLID and ocular manifestations have now been identified.     

色素失禁症在新生儿期的临床特点及基因分析

目的经过回顾性分析13例色素失禁症(incontinentia pigmenti,IP)在新生儿期典型的临床表现,探讨新生儿色素失禁的临床特点及核因子kappa-B必不可少的调节基因(the nuclear factor Kappa-B essential modulator gene,NEMO gene)突变。方法分析2005年1月-2014年8月西安市儿童医院收治的13例新生儿色素失禁症患儿的临床特点及4例患儿的NEMO基因突变检测结果。结果 13例患儿中只有1例男性。典型皮疹生后即可被发现或者生后不久出现,主要表现为红斑水疱期和色素沉着期。6例患儿外周血的嗜酸性粒细胞计数显著增加。6例皮肤活检显示嗜酸性粒细胞皮肤浸润与皮肤海绵层水肿伴随着色素失禁症特征性的一些凋亡细胞(角化不良细胞)。3例患儿有癫痫,其中2个伴有视网膜血管发育异常和闭塞。4例女性患儿确认与NEMO基因突变有关。结论色素失禁症(IP)是X连锁显性遗传性疾病,主要影响外胚层组织,大多为女性病人,男性病人少见。基因分析显示,NEMO基因的外显子4-10缺失与色素失禁症有关。