色素失禁症 色素失调症

翻译 司大勇 吉林大学生命科学学院 电话13321403210 粗略翻译,重要处请参照原文 Incontinentia pigmenti (IP), also known as Bloch-Sulzberger syndrome, is a disorder with dermatologic, ophthalmologic, neurologic, and dental findings. 色素失调症（IP），也称为Bloch-Sulzberger综合征，是皮肤科，眼科，神经和牙科的障碍 A few days after birth, the skin lesions appear on the extremities and trunk of the affected children as a linear pattern of erythema with vesicles and bullae. These lesions last for weeks and evolve into verrucous lesions that last for several months, until groups of hyperpigmented macules appear, usually on the trunk. Such hyperpigmented spots represent abnormal melanin granules dispersed throughout the dermis. 出生后的几天，受影响儿童的四肢和躯干上的皮损出现,模式为线性红斑，其上有水疱和大疱。这些病变持续几个星期，并演变成疣状，持续几个月，直到组的色素沉着斑通常出现在躯干上。这种色素沉着斑点代表整个真皮的异常黑色素颗粒分散。 The disease is inherited as X-linked dominant penetration. It is unfortunately lethal for male babies, but hypomorphic mutation, abnormal karyotypes and mosaicism provide three mechanisms for survival of males carrying a mutation at the IP locus 这种疾病的遗传X连锁显性渗透(渗透是什么意思?)。不幸的是，这种疾病的男性婴儿致死，但亚等位基因突变，异常染色体核型和嵌合体为承载在IP位点突变的男性的生存提供了三种机制. Ophthalmic manifestations of the disease have been reported in 20-85% of cases. Ocular findings are typically divided into retinal and nonretinal manifestations. The major reported nonretinal manifestations include strabismus, nystagmus, optic nerve atrophy, conjunctival pigmentation, iris hypoplasia and uveitis. Retinal manifestations include foveal hypoplasia, anomaly of retinal pigment epithelium, retinal vascular nonperfusion, neovascularization, vitreous hemorrhage and retinal detachment. 眼科疾病的表现已在20-85％的病例。眼的结果通常分为视网膜和非视网膜的表现。报道非视网膜表现主要包括斜视，眼球震颤，视神经萎缩，眼结膜色素沉着，虹膜发育不全和葡萄膜炎。视网膜的表现包括中央凹发育不全，视网膜色素上皮细胞异常，视网膜血管无灌注，新生血管，玻璃体出血和视网膜脱离。 Case Report 这段不翻译 Discussion 讨论 Bloch first used the term IP in 1926 to describe a patient with striking skin changes and an ocular pseudoglioma. 病名于1926年起源.. In 1938, Sulzberger had noted other ectodermal defects in association with this condition. 发现历史.. The diagnosis of IP is usually based on clinical examination. 通常,通过临床检查来诊断. IP is characterized by typical cutaneous lesions and in many patients by abnormalities of the eye and central nervous system. 色素失禁症的特点是典型的皮肤损害，在许多患者的眼睛和中枢神经系统的异常。 The skin lesions of IP may occur in four classical diagnostic stages: erythema, then vesicles and pustules (stage 1); verrucous lesions (stage 2), linear hyperpigmentation (stage 3), and pallor and scarring (stage 4). However, stages may overlap or not occur at all in the same patient. 色素失禁症的皮损可能会出现在四个经典的诊断阶段：红斑，然后水疱和脓疱（第一阶段）;疣状病灶（第2阶段），线性色素沉着（第三阶段），和苍白和疤痕（阶段4）。然而，在同一病人,四个阶段可能会重叠或不都发生。 A linear hyperpigmentation that follows the Blaschko lines usually leads to diagnosis of IP but it is not pathognomonic. 线性色素沉着随着Blaschko线发生,通常会导致患者诊断为色素失禁症，但它不是特异病征性的。(就是说,别的病也可能导致“线性色素沉着随着Blaschko线发生”的现象) Blaschko线的解释(不重要):Blaschko's lines, are skin lines invisible under normal conditions. They become apparent when some diseases of the skin or mucosa manifest themselves according to these patterns. They follow a "V" shape over the back, "S" shaped whorls over the chest, stomach, and sides, and wavy shapes on the head.[1]The lines are believed to trace the migration of embryonic cells.[2] HYPERLINK "http://en.wikipedia.org/wiki/Blaschko%27s_lines" \l "cite_note-2" [3] The severity of IP is related to ocular and neurological impairment. 色素失禁症的严重程度与眼和神经损伤相关。 Several authors mentioned the close relation of severe ocular and neurological involvement and authors have advocated neuroradiological explorations in the presence of any vascular retinopathy. In the literature, neurological manifestations have been reported in 18 to 36% of cases. 几位作者提到的严重眼（指眼科严重症状）和神经系统受累的密切关系（就是说，眼科的症状重，那么神经的也会重），他们主张存在任何血管性视网膜病变的患者作神经放射学检测。。在文献中，神经系统的表现已经被18至36％的病例中被报告。 Seizures, delayed psychomotor development, hemiplegia, hemiparesis, microcephaly, spasticity and mental retardation are the major reported neurological findings. 癫痫发作，精神运动性延迟发展，半身不遂，偏瘫，小头畸形，痉挛和精神发育迟滞，是被报告的主要的神经科症状。 In our case, though the dermatological findings were similar to previous presentations, neurological findings such as seizures, hemiplegia and spasticity were not detected. 不翻译 Cranial involvement may be unilateral or bilateral and cranial impairment is mainly on the contralateral side to the cutaneous findings. 颅脑损伤和皮肤损伤往往发生在对侧。 In the previous reports, various MRI findings have been reported, such as corpus callosum hypoplasia, neuronal heterotopia, and small- and large-vessel occlusions. 先前的报道中, 出现各种各样的MRI结果,比如胼胝体发育不全,神经元异位,和小和大的血管闭塞。 Focal cerebral, cerebellar and corpus callosum damage are typical findings. Severe cerebral lesions can be seen with cerebellar lesions. 局灶的大脑,小脑和胼胝体损伤是典型的。，，，， Involved regions may not be consistent with any vascular trace. 涉及区域可能与血管跟踪结果不一致。 If dermatological findings arise in the neonatal period and if the scalp and neck skin are especially involved, cranial impairment will be more severe than usual. 如果皮肤病学的结果出现在新生儿期,而且如果头皮和颈部皮肤也有,那么颅障碍会比往常更严重。 Cerebral lesions are stable and do not show any progression. 脑损伤是稳定的,不显示任何进展。 It has been hypothesized that corpus callosum hypoplasia is secondary to cerebral atrophy. 有假说认为胼胝体发育不全 是继发于脑萎缩。 Occasionally, giant cerebral aneurysm and hemimegalencephaly have been reported. 偶尔有巨大的脑动脉瘤和半侧巨脑症的病例报道。 In our patient as well and compatible with a previous report, MRS of brain involvement revealed a mild lactate peak representing chronic ischemic changes. 我们的病人,与之前的一份报告中,大脑参与的MRS揭示了一个温和的乳酸峰，代表了慢性缺血性改变。 This technique may help to distinguish cerebral involvement of IP from other possible demyelinating and inflammatory lesions. 这种技术可能有助于区色素失禁症和炎性脱髓鞘病变。 The neurological involvement can be well documented by MRI both on T1- and T2-weighted images. 色素失禁症的神经病变可以通过MRI（核磁共振成像）的T1和T2图像显示。 However, it is not recommended in all IP patients since patients may not have any neurological symptoms. 然而，不推荐所有患者作MRI核磁共振成像，如果没有任何神经症状的话。 Recently, Bryant and Rutledge reported a neurologically intact girl with abnormal neuroimaging findings. For the above-mentioned reasons, there is no reason to acquire neuroimaging in IP patients, if neurological and ocular findings are absent. 重复上面的话。 In our case, since the patient had severe neurological and ocular findings, we performed radiodiagnostic imaging. Similar to previous reports, there was volume loss consistent with focal atrophy on the left frontal lobe. Furthermore, the right hemisphere was more prominent than the left in all sections. The prominence of the right hemisphere in all sections, even in those sections without atrophy of the left side, led us to suspect right-sided mild hemimegalencephaly. The corpus callosum was atrophic but there was no evidence of gray matter heterotopia or any abnormality of the cerebellum. 不翻译 In the differential diagnosis of cutaneous lesions associated with cerebral atrophy, Sturge-Weber syndrome, Klippel-Trenaunay-Weber syndrome and Parry Romberg syndrome should be kept in mind. 在皮肤病变相关联的大脑萎缩的鉴别诊断时，Sturge-Weber综合症,Klippel-Trenaunay-Weber综合症和Parry Romberg综合症应牢记在心。 In Sturge-Weber syndrome train rail calcification, in Parry Romberg syndrome progressive cerebral atrophy, and in Klippel- Trenaunay-Weber syndrome arteriovenous anomalies are present. Sturge-Weber综合征时，火车轨迹钙化；Parry Romberg综合征时，进行性的脑萎缩；Klippel- Trenaunay-Weber综合征时，动静脉异常。 With these specific signs, neuroradiologic differentiation from IP can be easily managed.废话 In all of these syndromes, different cutaneous involvements are important landmarks for diagnosis. Proposed pathogenic mechanisms for the neurological lesions observed in IP have included inflammatory, developmental and infectious processes. 不翻 Recently, it has been suggested that the primary cause for the neurological lesions was small-vessel occlusion, and this theory could also explain the vascular abnormalities in the eyes of patients with IP。. 不翻 In IP, total blindness or permanent visual deficiency may occur secondary to retinal detachment, optic nerve atrophy, occipital lobe infarction, and macular infarction. 在色素失禁症,全失明或视力缺陷可能继发于视网膜脱离,视神经萎缩,枕叶梗塞,黄斑梗塞。 The main causes of non rhegmatogenous retinal detachment in childhood are premature retinopathy, persistent hyperplastic primary vitreous, Coat’s disease, retinal capillary hemangioma, retinoblastoma and IP. 在童年的非裂孔性视网膜剥离的主要的原因,是，不成熟的视网膜病变,持续增生性玻璃体, Coat’s disease,,视网膜毛细血管血管瘤,成视网膜细胞瘤和色素失禁症。 Because of retinal detachment association with retrolental mass, IP is also referred to as pseudoglioma. 由于视网膜剥离与晶状体后的物体有关，色素失禁症也被称为假神经胶质瘤 。 In our case, we evaluated the bilateral closed retinal detachment of the baby and our conclusion was that it was inoperable.不翻 According to Wald et al., like in premature retinopathy, laser ablation of the peripheral retina may be highly beneficial in retinal detachment in IP patients. 据瓦尔德等说, 类似在儿视网膜病变那样，对于色素失禁症患者的视网膜脱离，激光烧蚀周边视网膜可能大有益处。 Recent studies have focused on the importance of fluorescein angiographic findings in patients with IP. 最近几个研究针对色素失禁患者的荧光血管造影的重要性。 Fluorescein angiography may be very useful for detection of undetected macular abnormalities and may provide critical information in the planning of laser treatment. 萤光摄影检查可能是非常有用的，检测未被发现的黄斑病变，在规划激光治疗时可能提供重要的信息。 Usually the presence of leakage on fluorescein angiography is more pronounced in patients with retinopathy of prematurity than in those with IP. 看不懂 A tight ophthalmological examination schedule is recommended for early detection and management of these patients. 一个紧凑的眼科检查时间表推荐用于这些病人的早期检测和管理。 The eyes should be examined as soon as after birth as possible. 出生后应及早检查眼睛。 Follow-up at least monthly for three to four months, at three-month intervals for one year and twice yearly up to three years should be done. 后续三到四个月至少每月一次, 一年内三个月检查一次，三年内每半年检查一次。 This schedule could even be tightened further in patients with any retinal disease. 如有视网膜疾病，这个检查可以更频繁。 The gene for IP has been mapped to the NEMO (nuclear factor-kappaB [NF-kB] essential modulator) gene located at Xq28. NEMO is an important part of the NF-kB signaling pathway that controls expression of multiple genes including those for cytokines and chemokines. 致病基因为 Xq28的NEMO基因。 Mutation in NEMO accounts for 80% of cases, with most of these consisting of exons 4 through 10. The loss of NEMO activity leaves mutant cells vulnerable to apoptosis when exposed to tumor necrosis factor (TNF)-α. Mutation of this gene also leads to activation of eotaxin, an eosinophil chemokine. Eotaxin activation causes accumulation of eosinophils in and around vessels, resulting in vaso-occlusive findings in the eye and brain and vesicles in the skin. In experimental animals, it has been shown that NEMO-deficient mice show the features of human IP disease. Male NEMO knockout mice die from severe liver apoptosis because NF-kB remains inactive and thus fails to prevent the cellular lethality induced by TNF-α stimulation and female mice develop IP-like skin lesions. The pathophysiology of the retinal and cerebral problems has not yet been described in animal models. 80%病例发现NEMO基因突变。大多是外显子4-10缺失。实验鼠把NEMO基因弄坏，症状和人相似。 Association of dysmorphic auricula and some craniofacial anomalies in IP is a well-known subject. Our patient had no auricular malformation or facial anomaly. 研究色素失禁症的颅面畸形和变形耳廓是一个有名的主题。 Central auditory pathologies could accompany in patients with IP. 色素失禁症可能伴随中央听觉疾病。 Hence, auditory brainstem response (ABR) should be performed to consider the possible investigation of central auditory pathways or hearing abnormalities in the brainstem. In our patient, click ABR responses were consistent with normal hearing. Latency and amplitudes of waves were normal. We planned to evaluate our patient’s hearing parameters once a year to diagnose and habilitate the possible lateonset hearing loss. 因此,听性脑干反应(ABR)应该实行，考虑可能的调查中央听觉通路或听觉脑干异常。 The diagnosis of IP is initially based on clinical criteria. However, in histopathologic examinations, the presence of both eosinophilic spongiosis and apoptosis in the brain, eye and skin at birth are characteristic findings of IP. 色素失禁症的诊断：临床（目测？），而在病例检查时，在脑眼皮肤的出生就有的嗜酸性海绵样水肿 和细胞凋亡为该病的特征。 In the neonatal period, the presence of characteristic skin pigmentation, leukokoria, and neurological findings should lead to suspicion of this disease. 在新生儿时期，皮肤问题，白瞳症和神经异常发现应该作为该病的怀疑对象。 The follow-up of patients requires multidisciplinary collaboration and the primary goal should be the detection of ophthalmologic and neurological involvements as soon as possible. 后续的病人需要多学科协作，主要的目标应该是尽快检测眼科和神经系统。 Management of associated retinal pathologies may dramatically improve visual prognosis of patients. Need of neuroimaging should be kept in mind, in the presence of vascular retinopathy and retinal detachment. 治疗相关的视网膜疾病可能会大大改善视觉患者预后。应该牢记,在存在血管视网膜病变、视网膜脱离时候，需要神经影像学检查！