Incontinentia pigmenti and the eye.

PURPOSE OF REVIEW: Incontinentia pigmenti (IP) is a rare X-linked dominant phakomatosis that predominately presents with dermatologic manifestations but can also cause central nervous system and ocular abnormalities. Awareness of the ocular complications of IP is crucial to identify ocular abnormalities early and prevent permanent vision loss. RECENT FINDINGS: There have been significant recent advances in ocular diagnostic imaging in IP. Optical coherence tomography (OCT) has helped characterize outer plexiform layer abnormalities in the macula, which can help explain central vision loss in IP patients. OCT angiography (OCT-A) also identifies macular vascular changes that induce these foveal structural abnormalities and may supplement fluorescein angiography, the current standard of care to identify peripheral retinal ischemia and neovascularization for infants with IP. Additionally, recent studies have presented excellent anatomic outcomes years after laser photocoagulation to ischemic retina. Early data indicates that antivascular endothelial growth factor therapy can induce retinal revascularization, but runs the risk of late recurrent neovascularization and requires long-term monitoring. SUMMARY: Ophthalmic imaging is evolving in the evaluation of IP and is increasingly guiding treatment modalities. A particular focus on the ocular manifestations of IP has been the ideal treatment for retinopathy in this disorder.

Incontinentia Pigmenti: X-Linked Skin Disorder: A Case Report.

Incontinentia pigmenti (IP) is a rare X-linked neuroectodermal dysplasia affecting the skin, hair, teeth, nails, microvasculature, and central nervous system. Mutations in the IKBKG gene cause this disorder. Incontinentia pigmenti is found in 65-75 percent sporadic mutations and 25-35 percent familial cases. Most patients are female, as the disease is generally lethal in males. The condition often is identified secondary to skin presentations followed by the central nervous system (CNS) manifestations in the eye and brain within the first year of life. In addition to the skin changes, there may be defects in the hair, nails, and teeth. The uniqueness of the disorder and shared findings similar to other skin disorders complicate the diagnosis. Clinical findings point to an array of possibilities. Lack of information on family history complicates the time to diagnosis. With the confirmation of IP, a thorough evaluation with appropriate consultations improves outcomes where possible.

Incontinentia pigmenti / Bloch-Sulzberger syndrome: a case report.

Incontinentia pigmenti is a rare genodermatosis that almost exclusively affects females. The disease is caused by a mutation of the nuclear factor-κB essential modulator (NEMO) gene in the Xq-28 locus of the X chromosome. The disease can seriously affect various organs, most notably the central nervous system and eyes. Cutaneous manifestation in incontinentia pigmenti is often mild but is an important diagnostic criterion for the disease. Treatment of cutaneous symptoms of incontinentia pigmenti is often not needed because they can spontaneously resolve. However, it should be noted that early diagnosis through parameters such as cutaneous manifestations is important so that prompt diagnosis and intervention for other organs can be made to prevent further fatal complications in the future.

Incontinencia pigmentaria. Presentación de un caso / Incontinentia pigmenti. A case report

RESUMEN La incontinencia pigmentaria, también conocida como síndrome de Bloch-Sulzberger, es una rara genodermatosis ligada al cromosoma X, localizado en el Xq28. Afecta al sexo femenino y tiene diferentes expresiones clínicas en una misma familia. Es una enfermedad multisistémica, caracterizada por afectar de forma variable a los tejidos derivados del neuroectodermo, la piel, ojos, dientes y el sistema nervioso central. Las lesiones cutáneas son las más significativas desde el nacimiento, y la biopsia confirma el diagnóstico. Debido a la rareza de esta entidad, se presentó el caso de una lactante de un mes, con antecedente familiar de incontinencia pigmentaria, quien exhibía lesiones típicas en la piel desde la primera semana de vida, en diferentes fases, que siguen las líneas de Blaschko. Se constataron manifestaciones oculares y eosinofilia (AU).

ABSTRACT Pigmentary incontinence, also known as Bloch-Sulzberger syndrome, is a rare X chromosome-linked genodermatosis, located in Xq28. It affects the female sex and has different clinical manifestations in the same family. Ii is a multi-systemic disease characterized by affecting, in a variable way, the tissues derived from the neuroectoderm, the skin, the eyes, the teeth and the central nervous system. Skin lesions are the most significant ones since birth time, and skin biopsy confirms the diagnosis. Due to the rareness of this entity, we presented the case of a nursing female infant aged one month, with a family history of pigmentary incontinence, who presented typical lesions in the skin, since his first week of life, in different phases, following the lines of Blaschko. Ocular manifestations and eosinophilia were confirmed (AU).

Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti.

BACKGROUND: Incontinentia pigmenti (IP) is a rare multisystemic X-linked dominant genetic disorder characterized by highly diagnostic skin lesions. The disease can be misdiagnosed in infants, and complications affecting the eyes and/or the brain can be severe. Our objective was to highlight the urgency of an appropriate diagnosis and management strategy, as soon as the first symptoms appear, and the need for a well-codified monitoring strategy for each child. METHODS: An in-depth literature review using a large number of databases was conducted. The selection criteria for articles were literature review articles on the disease, case series and retrospective studies based on the disease, clinical studies (randomized or not) on treatment, articles discussing patient care and management (treatment, diagnosis, care pathways), and recommendations. The research period was from 2000 until 2018. A group of multidisciplinary experts in IP management was involved, issued from different healthcare providers of the European Network for Rare Skin Diseases (ERN-Skin). The final recommendations have been submitted to two patient representative associations and to a general practitioner and a neonatal specialist prior to their finalization. RESULTS AND CONCLUSION: The diagnosis of IP must be promptly performed to detect potential extracutaneous manifestations, thus allowing the timely implementation of specific therapeutic and monitoring strategies. Eye involvement can be a therapeutic urgency, and central nervous system (CNS) involvement requires a very rigorous long-term follow-up. Assessments and patient support should take into account the possible co-occurrence of various symptoms (including motor, visual and cognitive symptoms).

Incontinentia Pigmenti. / 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: A Summary Review of This Rare Ectodermal Dysplasia With Neurologic Manifestations, Including Treatment Protocols.

Incontinentia pigmenti is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene (formerly known as NEMO). There are 27.6 new cases per year worldwide; 65% to 75% are sporadic mutations, and 25% to 35% are familial. It is usually lethal in males, but females survive because of X-inactivation mosaicism. The disorder is typically identified by unique skin findings, a series of four stages that emerge throughout the first year of life. The central nervous system manifestations in the eye and in the brain cause the most disability. Defects of hair, nails, and teeth occur, and there can be other systemic involvement. Surveillance protocols for medical management have been established by the Incontinentia Pigmenti International Foundation. This article will summarize the existing knowledge of this condition and detail the protocols to help manage the care of the infant or child who presents with incontinentia pigmenti.

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

OBJECTIVE: Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. METHODS: In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. RESULTS: The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. INTERPRETATION: The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104.

A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases.

Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an in vivo screening system of random ligand libraries displayed on adeno-associated viral capsids to select brain-targeted vectors for the treatment of neurovascular diseases. We identified a capsid variant showing an unprecedented degree of specificity and long-lasting transduction efficiency for brain microvasculature endothelial cells as the primary target of selection. A therapeutic vector based on this selected viral capsid was used to markedly attenuate the severe cerebrovascular pathology of mice with incontinentia pigmenti after a single intravenous injection. Furthermore, the versatility of this selection system will make it possible to select ligands for additional in vivo targets without requiring previous identification of potential target-specific receptors.

Incontinentia pigmenti (Síndrome de BlochSulzberger) en un paciente varón. Reporte de un caso / Incontinentia pigmenti (Bloch-Sulzberger Syndrome) in a male patient. A case report

Incontinentia pigmenti es una rara genodermatosis ligada al cromosoma X caracterizada por lesiones ampollares distribuidas sobre las líneas de Blaschko. Esta se presenta en cuatro estadios: vesicular, verrugoso, hiperpigmentado y atrófico. Es más frecuente en mujeres por su letalidad en varones, aunque hay casos de sobrevivencia en ellos. Se presenta el caso de un varón de 30 días de nacido que presentó lesiones vesiculo-ampollares de distribución lineal siguiendo las líneas de Blaschko. Se le realizó una biopsia cutánea cuya conclusión fue incontinentia pigmenti en estadio vesicular. Este es el primer caso varón reportado en la literatura peruana...

Incontinentia pigmenti is a rare X-linked dermatosis characterized by bullous lesions distributed along Blaschko´s lines. Four clinical stages are recognized: blister, verrucous or wart like lesions, hyperpigmentation and atrophic lesions. We present the case of a 30-day old male patient who presented with blisters and bullous lesions distributed along Blaschko´s lines. A skin biopsy was performed that confirmed the diagnosis. This is the first report of a male patient in Peru with the syndrome...

Incontinentia pigmenti and hypomelanosis of Ito.

Incontinentia pigmenti (IP) is a rare X-linked dominant neurocutaneous disorder affecting ectodermal tissue: skin, eyes, central nervous system, hair, nails, and teeth. It is usually lethal for males in utero. The involved gene is NEMO, an essential component of the nuclear factor-kappa B (NF-κB) signaling pathway. Skin lesions are highly diagnostic, occurring in neonates, with a particular distribution on Blaschko lines. The severity of the disease is related to ocular and neurological impairment. The hallmark of ocular IP is retinal vasculopathy including peripheral retinal vascular nonperfusion, macular infarction and neovascularization, and preretinal neovascularization. CNS involvement consists of seizures, mental retardation, hemiparesis, spasticity, microcephaly, cerebellar ataxia, and coma. It often occurs in neonates. Some patients have persistent pharmacoresistant seizures throughout life. MRI findings consist essentially in: white-matter lesions; scattered cortical neuronal necrosis; multiple cerebral infarctions; cerebral atrophy, hypoplasia of the corpus callosum, encephalomalacia and neuronal heterotopia. A predominant role of vascular occlusive phenomena in small vessels is highly suspected. In fact several intricate mechanisms could be discussed: vascular, inflammatory, developmental mechanisms. Their role and predictive factors of IP CNS involvement in neonatal IP need to be better understood to identify effective innovative therapies. Hypomelanosis of Ito can occur in the neonate, infancy, or childhood, be isolated or diffuse, often following the Blaschko lines, and can fade in childhood or adulthood. It is due to reduced melanin in the epidermis. Eye, central nervous (mental retardation, epilepsy, language disabilities, motor system dysfunction, psychiatric symptoms including autism - with frequent cortical malformations including hemimegalencephaly and white matter involvement), and musculoskeletal systems can also be affected. Mosaicism with various chromosomal rearrangements has been reported.

Incontinencia pigmenti: a propósito de dos casos / Incontinentia pigmenti: report of two cases

La Incontinencia Pigmenti (IP) o síndrome de Bloch Sulzberger es un trastorno multisistémico neuroectodérmico, que afecta predominantemente al género femenino, cuya manifestación inicial incluye lesiones cutáneas que evolucionan por brotes. En ocasiones, se asocia a compromiso oftalmológico, neurológico y dentales parte del diagnóstico diferencial de lesiones ampollares en un neonato. Se presentan dos casos de IP diagnosticados en etapas cutáneas distintas, uno de ellos con compromiso neurológico.

Incontinentia Pigmenti (IP) or Bloch Sulzberger syndrome is a neuroectodermal multisystemic disorder, that predominantly affects women, whose initial manifestation includes skin lesions that evolve by outbreaks. Sometimes, is associated with ophthalmological, neurological and dental commitment. It is part of the differential diagnosis of bullous lesions in a newborn. We present 2 cases of IP diagnosed in different skin stages and one of them with neurological involvement.

Síndrome de Bloch-Sulzberger (Incontinentia pigmenti): características y aporte de un caso clínico / Bloch-Sulzberger´s syndrome (Incontinentia pigmenti): contribution with a case report

La incontinencia pigmentaria (IP) es una genodermatosis rara. Las lesiones cutáneas están presentes en todos los afectados y evolucionan en estadios. El primero es el eritemato-ampollar, cuyo diagnóstico diferencial incluye una gran variedad de enfermedades. Presentamos el caso de un neonato de sexo femenino, con vesículas presentes desde el nacimiento cuya biopsia cutánea confirmó el diagnóstico de IP.(AP)

Incontinentia pigmenti (IP) is a rare genodermatosis. Skin lesions, that are present in all patients affected, evolve in stages. The first is the erythematous blistering stage, wich differentialdiagnosis includes a wide variety of diseases. We present a case of a female neonate with blisters present at birth, where the skin biopsy confirmed the diagnosis of IP.

[Incontinentia pigmenti: a case study]. / Incontinentia pigmenti: à propos d'un cas.

Incontinentia pigmenti is a rare hereditary, dominant, X-linked disorder. It involves the skin, the teeth, the eyes and the central nervous system. The case we report is an infant girl aged 2 months. She had typical skin lesions associated with severe impairment of her left eye. We comment on the clinical, histological, genetic, and therapeutic characteristics of this rare disease. Ophthalmologic examination should be made early in order to diagnose ocular involvement at an early stage of the disease to provide for greater treatment possibilities.

Incontinentia pigmenti (Bloch-Sulzberger syndrome): a systemic disorder.

Incontinentia pigmenti (IP) is a rare inherited multisystem disorder characterized by a distinctive swirling pattern of the skin; defects of teeth, hair, and nails; and ophthalmic, central nervous system, and musculoskeletal abnormalities. It progresses through several well-defined stages. IP is transmitted as a dominant X-linked trait with variable expressivity, but many--if not most--cases are sporadic. IP has been shown to result from mutations in the NEMO gene that completely abolish expression of NF-kappaB essential modulator. The diagnosis of IP typically is made based on characteristic clinical findings. Molecular analysis of the NEMO gene is now possible, as is analysis of skewed X-chromosome inactivation, which can further reduce diagnostic confusion. A number of disorders, including hypomelanosis of Ito, should be considered in the differential diagnosis. The considerations vary according to the stage of IP. Careful head-to-toe clinical evaluation is critical in the evaluation of a child with suspected IP given the frequent multisystem involvement. A multidisciplinary approach including dermatology, ophthalmology, neurology, and dental consults is typically warranted. The skin manifestations of IP do not require specific treatment other than reassurance; spontaneous resolution of the lesions usually occurs.

[Proposal for a protocol for the staging of incontinentia pigmenti in pediatric age]. / Proposta di un protocollo per la stadiazione della Incontinentia Pigmenti in età pediatrica.

Incontinentia Pigmenti (IP) is an X-linked dominant disorder of skin with neurologic and ophthalmologic involvement. IP predominantly affects females because the mutations are usually lethal in males in utero. IP is characterized by abnormalities of neuroectodermal tissues. IP is caused by mutations in a gene called NEMO, which is required to activate the NF-kB pathway. We present a diagnostic protocol for IP and a meta-analysis of the clinical spectrum of IP in 82 patients cited by MEDLINE in the European literature from 2000 to 2006.