Incontinentia pigmenti with intracranial arachnoid cyst: A case report

BACKGROUNDIncontinentia pigmenti (IP) is a rare X-linked dominant genetic disorder that can be fatal in male infants. It is a disease that affects many systems of the human body. In addition to characteristic skin changes, patients may also have pathological features of the eyes, teeth, and central nervous system. Therefore, the lesions in these systems may be the first symptoms for which patients seek treatment. To date, no cases of IP complicated by intracranial arachnoid cyst (IAC) have been reported. This paper aims to report a case of IP with IAC in order to share the diagnosis and treatment experience of this rare case with other clinicians. CASE SUMMARYAn 11-year-old female patient suffered intermittent limb convulsions for five months and was sent to hospital. In the initial stage, the patient was considered to have primary epilepsy. Further investigation of the patient''s medical history, physical examination and imaging examination led to the diagnosis of IP combined with intracranial space-occupying lesions, and secondary epilepsy. The patient was treated with craniotomy, and postoperative pathology revealed an IAC. The patient recovered well after craniotomy and had no obvious surgery-related complications. During the follow-up period, the patient did not have recurrent epilepsy symptoms.CONCLUSIONIP is a multi-system disease that presents with typical skin lesions at birth, but the long-term prognosis of this disease depends on the involvement of systems other than the skin, especially nervous system and ocular lesions.     

Incontinencia pigmenti

Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare neuroectodermal dysplasia. It is an X-linked dominant disorder caused by mutations in the IKBKG/NEMO gene on Xq28. Approximately 80% of patients have a deletion of exons 4 to 10. Incontinentia pigmenti has an estimated incidence of 0.7 cases per 100,000 births. In hemizygous males, it is usually lethal, while in females, it has a wide spectrum of clinical manifestations. Incontinentia pigmenti is a multisystemic disease that invariably features skin changes. These changes are the main diagnostic criteria and they evolve in 4 stages, in association with other abnormalities affecting the central nervous system, eyes, teeth, mammary glands, hair, nails, skin, and other parts of the body. The aim of this brief review is to highlight the clinical features of this genodermatosis and underline the importance of case-by-case interdisciplinary management, including genetic counseling.     

Incontinentia pigmenti in a male (XY) infant with long‐term follow up over 8 years

Incontinentia pigmenti (IP) is an X‐linked genodermatosis affecting the skin and other sites, including the teeth, nails, hair, eyes and nervous system defects in female patients. Generally lethal in males, there are only a few known cases of males surviving this condition. Nuclear factor (NF)‐κB essential modulator (NEMO), also known as inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG), constitutes an essential activator of NF‐κB. Over 80% of female patients with IP carry a common deletion mutation involving exons 4–10 of the IKBKG/NEMO gene. We present the case of a male infant (XY) with IP with no concomitant complications. Polymerase chain reaction (PCR) assay showed that the exon 4–10 deletion band was significantly stronger in the skin sample than in blood. Subsequently, long‐range PCR was performed periodically to confirm the spontaneous regression of mutant cells from his blood. Over a period of 6 years, the 2.6‐kb mutant band gradually became weaker, but we did not confirm complete regression. Our patient was a healthy, 8‐year‐old male child with no complications despite the presence of a 2.6‐kb mutant band in his blood. Further follow up is necessary to assess for complications that may develop later.     

Abnormal Cutaneous Nerves in Incontinentia Pigmenti

Cutaneous nerves showed multiple ultrastructural abnormalities in a patient with incontinentia pigmenti. Fetal nerve bundles were seen both in the dermis and entering the epidermis. A cell with some Schwann cell features was identified above the basal layer amid keratinocytes. Dermal melanophages were in close apposition to Schwann cells. All of these features suggest that neural structures may be abnormal in incontinentia pigmenti and play a role in transfer of melanin from epidermis to dermis.     

Blaschko line analogies in the central nervous system: A hypothesis

In X-chromosome-linked skin disorders the pattern of involvement follows Blaschko lines. Patterns of changes analogous to cutaneous Blaschko lines in different X-linked diseases existed in other organs. There is no commonly accepted analogy to Blaschko lines in the central nervous system (CNS). The objective of this study was to consider a hypothesis of the existence of Blaschko lines in the CNS in the example of incontinentia pigmenti (IP). Articles were analyzed in which brain imaging methods were used in IP patients with CNS anomalies. In IP patients with neurological signs brain lesions usually were localized and extended radially. Affected areas did not correspond to territories vascularized by any determined artery. Radially distributed brain lesions morphologically match the radial unit model of cortical development. It can be proposed that in IP in CNS Blaschko line analogies, similar to those in the skin, represent the trace of development of the clone of neurons arising from the cell marked with IKBKG mutation. The hypothesis of the existence of Blaschko line analogies in CNS is supported by radially distributed CNS image findings in IP, the radial unit model of CNS development, and the common embryonic origin of skin, CNS, and eyes.     

一个色素失禁症家系的NEMO基因和假基因△NEMO缺失突变分析

目的 用长链聚合酶链反应进行检测家族性色素失禁症(incontinentia pigmenti,IP)患者的NEMO基因的缺失突变.方法 收集一色素失禁症家系的临床资料,选取NEMO基因特异引物In2/ff3R和假基因△NEMO的特异引物Rev-2/JF3R,采用长链聚合酶链反应对家系内成员NEMO基因和假基因△NEMO的缺失位点进行检测,同时对80名无血缘关系健康对照者的该位点进行同样检测.结果 所有患者皆有NEMO基因和假基因△NEMO基因共有序列NEMO△4-10缺失,而在家系内非患者以及80名正常对照者中均未发现NEMO基因和假基因△NEMO的共有序列NEMO4△-10缺失.结论 该家系为一个典型遗传早现现象的IP家系,NEMO基因和△NEMO的缺失突变导致其发病.长链PCR扩增技术可用于检测NEMO基因的缺失突变,对于遗传咨询具有一定的应用价值.     

Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia pigmenti presenting with unilateral nystagmus

Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG, leading to functional loss of nuclear factor kappa B (NF‐?B). We report the case of a 6‐month‐old female child with IP who presented with unilateral nystagmus and was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced understanding of the relationship between NF‐?B, along with its upstream regulators, and tumorigenesis may shed light on whether a subset of patients with IP may be at increased risk for neoplasia.     

色素失禁症临床表型与NEMO基因突变7例并文献复习

目的:探讨色素失禁症（IP）在中国儿童的临床表型及NEMO基因突变特点。方法:分析2009至2012年复旦大学附属儿科医院（我院）收治的7例IP患儿临床表型和NEMO基因突变,检索PubMed、Web of Science、中国知网、维普中文科技期刊数据库及中国生物医学文献数据库,检索研究对象为中国人的IP文献,汇总中国IP患儿临床表型和NEMO基因的突变数据。结果:我院7例IP患儿临床表型除有典型的皮肤损害外,主要还有神经系统和眼部受累,5例NEMO基因共有序列NEMO△4-10缺失,2例外显子测序,未发现致病性突变位点,其中1例发现1个纯合SNP。汇总我院7例和文献检索到的69例中国IP患儿（76例）数据显示,女68例,男8例;92.1%（70例）在新生儿期发病,21.1%（16例）有阳性家族史;均有皮肤受累,53.9%（41/76）神经系统受累,24.2%（16/66）眼部受累,39.6%（19/48）牙齿受累,31.0%（22/71）毛发受损,7.9%死亡（6/76）,其他少见临床表型：先天性心脏病3例,骨骼发育缺陷、环状胰腺和肺囊变各1例;58.3％（21/36）血嗜酸性粒细胞升高;皮肤组织活检阳性率达95.7%（22/23）。48/76例行基因检测的IP患儿中,30/48例（62.5％）发现有NEMO基因突变,其中大片段缺失27例（假基因缺失3例）,点突变2例和单个碱基缺失1例。结论:中国IP患儿散发病例占多数,绝大多数在新生儿期即发现典型的皮肤损害,其次为神经系统、牙齿受累和眼部受累。皮肤病理活检阳性率非常高。NEMO基因的突变检出率为62.5%,可对患儿进行合理的产前诊断和早期干预。     

46-XY型色素失禁症伴中枢神经系统受累一例

患儿男,3岁。因躯干部色素斑伴痒2年余就诊于我院皮肤科门诊。追问病史,患儿于出生后2周躯干部出现红斑,上有水疱呈线状排列,皮损此起彼伏,迁延不断,1个月后逐渐消退,继水疱后在原有皮损部位出现形状不规则褐色疣状丘疹。12个月时患儿四肢无规律性经常抽动伴有喂乳困难,持续数秒,可自行缓解,发作无规律,就诊于儿科门诊诊断为“癫痫”。患儿智力明显落后于同龄人,2岁多能说简单话,不能连成句,2岁半会走,至今34个月仍步态不稳。患儿无高热或外伤史。父母非近亲结婚,否认家族中类似疾病发病史……     

Retinosis pigmentaria sine pigmento. Inicio con edema macular

Case reportA 25-year-old woman, with metamorphopsia in her left eye of one year onset. The examination revealed a bilateral cystoid macular oedema (CME) and vascular attenuation. We describe the diagnostic tests, as well as differential diagnosis and treatment response with carbonic anhydrase inhibitors.DiscussionThe retinitis pigmentosa sine pigment is a subtype of atypical retinitis pigmentosa characterised by the absence of pigment deposits. The night blindness is milder, and perimetric and electroretinographic impairment is lower. CME is an important cause of central vision loss, and responds to anhydrase carbonic inhibitors.