The Prevalence of Retinal Disease and Associated CNS Disease in Young Patients with Incontinentia Pigmenti.

PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, and 3 = retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51%) by indirect ophthalmoscopy and 26 of 35 patients (74%) by FA (P = 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z = -2.12, P = 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.

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).

Incontinencia pigmentaria en madre e hija / Mother - daughter Incontinentia pigmenti

Introducción: La incontinencia pigmentaria es una genodermatosis poco frecuente, con herencia dominante ligada al cromosoma X, que se presenta casi exclusivamente en mujeres. Objetivo: Informar un caso de incontinencia pigmentaria familiar (madre e hija), trastorno neuroectodérmico sistémico infrecuente. Presentación del caso: Lactante femenina remitida del servicio de neurología a la consulta especializada de dermatología en el Hospital William Soler, por alteraciones en el desarrollo psicomotor y crisis epilépticas con lesiones vegetantes hiperpigmentadas que siguen las líneas de Blaschko. En la madre se detectaron lesiones atróficas con una disposición similar. Conclusiones: Esta rara enfermedad debe sospecharse por erupción cutánea que sigue las líneas de Blaschko, habitualmente presentes en el nacimiento y que evoluciona en etapas consecutivas características. Resaltamos la importancia del asesoramiento genético, con el fin de prevenir futuras generaciones afectadas, así como el manejo multidisciplinario en esta genodermatosis(AU)

Introduction: Incontinencia pigmenti is a rare genodermatoses with dominant inheritance linked to X chromosome that occurs almost exclusively in women. Objective: To report a case of family incontinentia pigmenti (mother and daughter), which is a systemic neuroectodermal disorder rare in pediatrics. Case presentation: Female infant referred from the neurology service to the dermatology specialist in William Soler Hospital due to alterations in the psychomotor development and epileptic seizures with hyperpigmented vegetative lesions that follow the Blaschko lines. In the mother, atrophic lesions were detected with a similar distribution. Conclusions: This rare disease should be suspected by rash that follows the Blaschko lines, usually present at birth and that develops in characteristic consecutive stages. We emphasize the importance of genetic counselling in order to prevent future generations to be affected, as well as the multidisciplinary management in this genodermatoses(AU)

The Incontinentia Pigmenti Genetic Biobank: study design and cohort profile to facilitate research into a rare disease worldwide.

Incontinentia pigmenti (IP; OMIM#308300) is a rare genetic disease resulting in neuroectodermal defects, which can lead to disability. At present, there is neither definitive cure available nor are there any sufficiently reliable insights to predict the severity of the disease. We launched the Incontinentia Pigmenti Genetic Biobank (IPGB) project ( http://www.igb.cnr.it/ipgb ) in 2015 to establish a large-scale deposit of biological samples, to provide detailed clinical information about children diagnosed with IP and to facilitate research. We have built a cohort comprising samples of 381 clinically confirmed patients with IP and 633 healthy individuals recruited through IP patients' associations. The collection includes 269 trios, 83 duos, and 95 families with at least two affected members and represents an extensive dataset (200 cooperative medical institutes, 139 in Italy and 61 worldwide) that enables a comprehensive phenotyping. Joining the IPGB guarantees all participants access to the results including the genetic testing of IP and the long-term storage of the samples. The IPGB is the largest IP sample collection and one of the largest rare-disease-oriented collections in the world and will be open to requests for access to data by the national and international scientific community.

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.

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-ĸB). 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-ĸB, 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.

Incontinentia pigmenti (Bloch-Sulzberger syndrome).

Incontinentia pigmenti (IP; Bloch-Sulzberger syndrome; OMIM #308300) is an X-linked dominant neurocutaneous disorder with presumed male lethality. It is usually diagnosed in female newborns based on skin features (erythematous, vesicular, or bullous eruption in linear streaks). The skin lesions evolve into a verrucous stage, followed by atrophy and scarring, leaving linear areas of hypopigmentation and hyperpigmented macules in bizarre patterns following Blaschko's lines. Systemic and neurologic complications include focal seizures and hemorrhagic cerebral infarction in infants, and retinal vasculopathy leading to blindness. Hypodontia, conical or pegged teeth, and linear areas of alopecia persist into adulthood. IP is caused by mutation of the IKBKG/NEMO gene on Xq28. Deletion of exons 4 to 10 (NEMOΔ4-10) accounts for about 80% of cases (familial and sporadic). NEMO mutation leads to loss of function of NF-κB, a critical protein that modulates cellular proliferation, apoptosis, and response to proinflammatory factors, leading to the characteristic features of IP. In female carriers, selective loss of cells expressing the mutant X-chromosome results in completely skewed X-inactivation in the majority of cases. Study of mouse models in which various components of the NF-κB pathway (including NEMO) have been knocked out has contributed significantly to our understanding of disease pathogenesis.

Incontinentia Pigmenti: A Comprehensive Review and Update.

Incontinentia pigmenti (IP) is a rare syndrome with skin lesions, ocular abnormalities in the retina and elsewhere, central nervous system abnormalities, and teeth defects. The authors present an updated review of the literature, highlighting diagnosis, epidemiology, pathophysiology, clinical features, and management of IP. IP is an X-linked dominant syndrome with an incidence of 0.0025%; most patients are female. IP is caused by a mutation in the IKBKG gene, causing a loss of function of NF-κß, leaving cells susceptible to apoptosis from intrinsic factors. The cardinal feature of IP is four stages of skin distinctive lesions. Of those with IP, 36.5% have detectable eye pathology and 60% to 90% of those have retinal issues. Peripheral avascularity and macular occlusive disease commonly occur. The authors performed a comprehensive review of Medline from 1947 to 2014. All papers mentioning IP in ophthalmologic journals were reviewed as well as applicable publications from other medical specialties.

Incontinentia pigmenti: report on data from 2000 to 2013.

We report here on the building-up of a database of information related to 386 cases of Incontinentia Pigmenti collected in a thirteen-year activity (2000-2013) at our centre of expertise. The database has been constructed on the basis of a continuous collection of patients (27.6/year), the majority diagnosed as sporadic cases (75.6%). This activity has generated a rich source of information for future research studies by integrating molecular/clinical data with scientific knowledge. We describe the content, architecture and future utility of this collection of data on IP to offer comprehensive anonymous information to the international scientific community.

Asthma associated with incontinentia pigmenti and Fanconi anemia: variable airflow limitation without cellular bronchitis.

Airway inflammation is considered a central component of asthma and, therefore, international guidelines recommend antiinflammatory medications. We describe the clinical history of a 34-year-old woman with airway hyperresponsiveness and asthma who had a reduced ability to mount an inflammatory response due to two unrelated and rare genetic conditions: Fanconi anemia and incontinentia pigmenti. Absence of eosinophils in blood and sputum led to a successful reduction in the dose of corticosteroids without loss of asthma control demonstrating the clinical utility of monitoring treatment using biomarkers and the importance of recognizing the components of airway diseases that contribute to symptoms.

Neurological findings in incontinentia pigmenti; a review.

Incontinentia Pigmenti is a rare X-linked multisystem disorder with well described and pathognomonic skin manifestations. Neurological manifestations are found in 30% of IP patients, forming one of the major causes of morbidity and mortality of the condition. In this review, clinical and brain imaging data of 45 IP patients with a neurological phenotype are reviewed. Several clinical presentations could be identified, comprising seizures, infantile encephalopathy, acute disseminated encephalomyelitis and ischemic stroke. Most neurological features presented during the neonatal period. No patients presented during adolescence or at adult age. Seizures of different type are reported in about 20% of the patients at young age and seem to correlate with the degree of cerebrovascular damage. Brain MRI findings include periventricular and subcortical white matter disease, haemorrhagic changes, corpus callosum hypoplasia, cerebral atrophy and cerebellar hypoplasia. Ocular findings comprise a range of retinal vascular changes and optic atrophy, but also developmental defects like microphthalmia and cataract. Most findings may reflect changes following brain injury. Both (ischemic) vascular and inflammatory components may play a role in the cerebral and ocular phenotype. However, a role of disturbed apoptosis during development may also be a contributing factor.

NEMO syndrome (incontinentia pigmenti) and systemic lupus erythematosus: a new disease association.

Congenital diseases are increasingly being recognised in adults because of clinical mimicry, variable clinical picture or rarity of the disease; pregnancy is a valuable diagnostic occasion. The present case is the first report of an association report between NEMO syndrome (an acronym of the mutated, non-functioning gene, NF-kB essential modulator), a rare X-linked disease, characterised by developmental anomalies, immunodepression and skin lesions, and systemic lupus erythematosus (SLE). A 35-year-old patient affected by SLE sought clinical advice in the 8th week of gestation. The diagnosis of SLE dated back to the age of 24, when multisystemic manifestations (pleuropericarditis, weight loss, alopecia, skin involvement, joint pain, kidney involvement) were observed. She had been treated with steroids since 1999; immunosuppressive drugs had been added for short periods. Developmental anomalies were present, including oligodontia, retinal problems, anomalies of the corpus callosum and pes planovalgus. Family history included multiple miscarriages, dental malformations and oligodontia and skin blistering in the first months of life. On these bases, incontinentia pigmenti (IP; or NEMO syndrome) was diagnosed and confirmed by genetic testing. The NEMO gene is implicated in immune deficiencies as well as in autoimmune diseases. This report may suggest a role for NF-kB essential modulator in the pathogenesis of SLE, in the context of the complex immunologic deficiencies increasingly associated with autoimmune diseases.

Incontinentia pigmenti--ophthalmological observation of a series of cases and review of the literature.

AIM: The aims of this study were to make an inventory of the disease in Ireland, to acquire better knowledge of the relationship between genetic makeup and phenotypic ocular presentation and, finally, through literature review and personal experience, to establish clear guidelines on best practice in the management of children with this rare condition both in terms of screening and follow-up. METHODS: All patients who attended the dermatology and genetic clinic in Our Lady's Hospital for Sick Children, Crumlin, with incontinentia pigmenti (IP) were contacted and invited to attend the eye clinic for ocular assessment. Children who were already attending the ophthalmic services before commencement of the study had their charts reviewed for assessment. RESULTS: 11 of 19 patients agreed to attend the clinic for ocular assessment. Of these patients, nine had genetic testing. The mean age of the patients at the examination was 8 years (3 months to 29 years). In 10 patients, IP was the result of a spontaneous mutation, whereas the condition was inherited from an affected mother in one patient. Of the 11 patients with IP, 5 have visually significant ocular findings (47%). We describe the case history of four of these children briefly to outline the severity of this condition. CONCLUSION: Our patients had a significant percentage of ocular abnormalities (47%). We have outlined an examination schedule for patients with and without retinal pathology and recommend fluorescein angiography in patients with retinal pathology to fully determine the extent of ischaemia. Like other studies, early treatment with peripheral retinal photocoagulation to reduce the risk of retinal detachment is recommended in this study.

Incontinentia pigmenti in boys: a series and review of the literature.

Incontinentia pigmenti is a rare X-linked genodermatosis, often associated with male lethality in utero. Occurrences of this disease in boys have been reported, however, its clinical phenotype has not been well characterized. The purpose of this study was to report on additional instances of incontinentia pigmenti in boys and to review the clinical, laboratory, and molecular characteristics of all published such patients. A retrospective chart review and Medline search using the keywords incontinentia pigmenti, males, and NEMO gene was undertaken. Six new boys with incontinentia pigmenti were found in our database and 36 more were previously reported in the literature. The vesiculo-bullous stage was the most frequent clinical presentation at diagnosis (80%). Fifteen percent of patients had an initial unilateral presentation. Recurrences of this stage were noted in 16%. Stages 2 and 3 of the disease were present in only 72.5% and 75% of patients, respectively. Only 15% of the boys had a documented stage 4. Extracutaneous manifestations were also documented (30% - central nervous system manifestations, 35% - eye involvement, 30% - alopecia, 40% - teeth anomalies). Thirty two percent of boys had peripheral eosinophilia. Only five had evidence of NEMO gene mutation. The male phenotype has clinical features similar to those of the female phenotype. Unilateral presentation is a distinct occurrence in boys, especially in early stages. Anomalies are the most common extracutaneous findings, followed by eye, hair, and central nervous system abnormalities.

Estudio de incontinentia pigmentien España. Nueva mutación del gen NEMO asociada a inmunodeficiencia transitoria / No disponible

No disponible

Estudio de incontinentia pigmenti en España. Nueva mutación del gen NEMO asociada a inmunodeficiencia transitoria / No dispnible

No disponible

No disponible

Incontinencia Pigmentaria. Consideraciones odontoestomatológicas: profilaxis y terapéutica / Incontinentia pigmenti. Odontostomtomatologics considerations: prevention and therapeutic

La incontinencia pigmentaria es una rara enfermedad, familiar, transmisión genética ligada al cromosoma X, de aparición casi exclusiva en mujeres, afectación cutánea muy típica y anomalías que afectan al pelo, dientes, ojos, sistema nervioso central, con una importante incidencia en las estructuras estomatognáticas tanto cuantitativa como cualitativamente. Los dientes se ven afectados en el 50-80% de los pacientes. Existe un retraso en la erupción dental, ausencia parcial o total de dientes, formas anormales de los mismos, dientes impactados, mal oclusiones. Por tanto, se considera importante la prevención en estos pacientes insistiendo en la higiene oral, control de caries, revisiones orales periódicas, etc.. Se hace una exposición de las distintas opciones de tratamiento para obtener una armonía, una funcionalidad y estética dental aceptables (AU)

Incontinentia pigmenti is a rare, family disorder of genetic transmisión linked to the X chromosome which appears almost exclusively in females; it causes skin disorders and anomalies that affect hair, teeth, eyes and the central nervous system. Teeth are affected in 50-80% of patients. Patients are late in teething, some or all teeth maybe lacking, those that exist may have malformations, maloclusions. Therefore prevention is of ut most importance in these patients, with special attention given to dental hygiene, control of tooth decay, regular check-ups, etc..The different options for treatment will be examined in order to obtain acceptable dental harmony, functioning and aesthetics (AU)

Ocular manifestations of incontinentia pigmenti.

PURPOSE: The study aimed to evaluate the ocular manifestations in patients with incontinentia pigmenti (IP). METHODS: Thirty patients from different parts of Sweden participated. Orthoptic and ocular examinations were performed as well as evaluation of refraction and visual acuity. RESULTS: Ocular manifestations, probably associated with IP, were found in 77% (23/30) of the patients. Thirteen had serious or vision-threatening eye manifestations in one eye, of whom 7 were totally blind in that eye from retinal detachments. Ten patients had minor retinal and/or corneal changes. CONCLUSION: Ocular lesions in patients with IP may be serious and lead to blindness because of retinal disease. Ophthalmological follow-up is essential in the neonatal period and such a programme is recommended.

Incontinencia pigmenti: sindrome de Blach-Sulzberger; primer caso en Panamá / Incontinentia pigmenti: Sulzberger-Bloch syndrome; first case in Panamá

La Incontinencia Pigmenti o síndrome de Bloch-Sulzberger es una rara genodermatosis que tiene importancia para el pediatra, neurólogo, dermatólogo y genetista. Los autores presentan el primer caso reportado en la República de Panamá y contribuyen con uno más a la casuística mundial por la poca frecuencia de dicha enfermedad

Incontinencia pigmenti: sindrome de Blach-Sulzberger; primer caso en Panamá / Incontinentia pigmenti: Sulzberger-Bloch syndrome; first case in Panamá

La Incontinencia Pigmenti o síndrome de Bloch-Sulzberger es una rara genodermatosis que tiene importancia para el pediatra, neurólogo, dermatólogo y genetista. Los autores presentan el primer caso reportado en la República de Panamá y contribuyen con uno más a la casuística mundial por la poca frecuencia de dicha enfermedad (AU)