Incontinentia pigmenti: genodermatosis multisistémica / Incontinentia pigmenti: multisistemic genodermatosis

Resumen La incontinentia pigmenti es una genodermatosis ligada al cromosoma X, generalmente letal en los hombres. Está causada por una mutación con pérdida de función en el gen IKBKG (inhibitor of kappa polypeptide gene enhancer in B cells kinase gamma), que impide que la proteína NFкβ (nuclear factor kappa-light-chain-enhancer of activated B cells) migre al núcleo y comience la transcripción de factores que amplifican la respuesta inmunitaria y previenen la apoptosis. Por tanto, las células mutantes se vuelven vulnerables a la apoptosis cuando son expuestas a citocinas y provocan vaso-oclusión e isquemia de tejidos como la piel, el sistema nervioso central y la retina. Las lesiones dermatológicas son características; se distribuyen a lo largo de las líneas de Blaschko, las cuales siguen el patrón de migración de las células de la piel en la embriogénesis, y ocurren en el 100% de los pacientes. Las manifestaciones cutáneas aparecen en una secuencia de cuatro fases que inicia desde el nacimiento: vesicular, verrucosa, hiperpigmentada e hipopigmentada. Estas lesiones son relevantes, puesto que orientan al clínico hacia el diagnóstico. Además, se acompañan de anomalías neurológicas, como crisis convulsivas, y múltiples manifestaciones oftalmológicas, como el desprendimiento de la retina. Los pacientes con incontinentia pigmenti, pero sin compromiso oftalmológico o neurológico clínicamente significativo, tienen un pronóstico bueno y una esperanza de vida normal. Las anomalías que se presentan son permanentes, lo que puede generar preocupación en los pacientes.

Abstract Incontinentia pigmenti is an X-linked genodermatosis generally lethal in males; thus, it presents almost exclusively in females. It is caused by a loss-of-function mutation in the IKBKG (inhibitor of kappa polypeptide gene enhancer in B cells, kinase gamma) gene that prevents the NFкβ (nuclear factor kappa-light-chain-enhancer of activated B cells) protein from migrating to the nucleus to begin the transcription of factors that amplify the immune response and prevent apoptosis. Consequently, mutant cells become vulnerable to apoptosis when exposed to cytokines and, in turn, lead to vaso-occlusion and ischemia of tissues, such as the skin, the central nervous system and the retina. Dermatological lesions are characteristic and occur in 100% of patients; they are distributed along Blaschko lines, which follow the pattern of migration of skin cells in embryogenesis. The cutaneous manifestations follow a sequence of four phases since birth: vesicular, verrucous, hyperpigmented and hypopigmented. These lesions are relevant for the disease because they guide the clinician towards the diagnosis. Additionally, they are accompanied by neurological abnormalities, such as seizures, and multiple ophthalmological manifestations, such as retinal detachment. Incontinentia pigmenti patients with no clinically significant ophthalmic or neurological compromise have a good prognosis and a normal life expectancy. The abnormalities present are permanent, which can be a cause of concern for the patients.

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)

Manifestação ocular incomum em paciente com incontinência pigmentar / Unusual ocular manifestation in a patient with incontinentia pigmenti

RESUMO Incontinência pigmentar, também conhecida como síndrome de Bloch-Sulzberger, é uma doença rara de herança dominante ligada ao X cujas manifestações clínicas incluem lesões dermatológicas típicas combinadas com acometimento neurológico, oftalmológico e dentário. Alterações oculares são comuns e variadas, sendo o acometimento da retina o mais frequente e associado a perda visual severa. Foi relatado um caso de uma criança com perda visual grave decorrente de glaucoma, sem alteração retiniana significativa.

ABSTRACT Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is a rare dominant X-linked inheritance disease whose clinical manifestations include typical dermatological lesions combined with neurological, ophthalmic and dental involvement. Ocular involvment is common and diverse and retinal changes are the most frequent and associated with serious visual loss. We reported a case of a child with severe visual loss due to glaucoma, with no significant retinal changes.

Incontinencia pigmenti en madre e hija: relato de caso clínico / Mother and daughter incontinentia pigmenti: case report

Incontinentia pigmenti (IP) is a rare genodermatosis linked to the X chromosome. It affects variably all tissues derives from neuroecthoderm such as skin, hair, nails, eyes and central nervous system. Early diagnosis allows the study of eventual multisystem involvement. Clinical case: We describe a 6 m.o. girl, controlled from the first week of life for a dermatological feature characterized by linear lesions, which were vesicular, then verrucous, and finally hyperpigmented. IP diagnostic family, determined by maternal history of similar lesions.

La incontinentia pigmenti (IP) es una genodermatosis rara ligada al cromosoma X. Afecta en forma variable a los tejidos derivados del neuroectodermo, como la piel, pelos, uñas, ojos y el sistema nervioso central. Su conocimiento y diagnóstico precoz permite estudiar un eventual compromiso multisistémico. Describimos el caso de una niña de 6 meses de edad, controlada desde la primera semana de vida por un cuadro dermatológico caracterizado por lesiones lineales vesiculosas, verrucosas y posteriormente hiperpigmentadas. Se plantea el diagnóstico de IP familiar, determinado por antecedentes maternos de lesiones similares.

Utility of molecular studies in incontinentia pigmenti patients.

The diagnosis of incontinentia pigmenti (IP) is fairly easy in the presence of classical features, but can be difficult in cases with partial or non-classical features, especially in the parents. The demonstration that the disease is caused by mutations in the NEMO gene, has remarkably improved genetic counselling for this disorder. We present four families of IP in whom molecular studies established an unequivocal diagnosis in the affected daughters, and showed two mothers to be carriers, thus allowing accurate genetic counselling and prenatal diagnosis.

Incontinentia Pigmenti in a Newborn with NEMO Mutation

Incontinentia pigmenti (IP) (OMIM #308300) is a rare X-linked dominant neuroectodermal multisystemic syndrome due to mutations in the gene for NF-kappaB essential modulator (NEMO). A term newborn girl who was born with erythematous vesicular eruptions developed recurrent seizures during the first and second weeks of her life. The serial MRIs demonstrated diffuse, progressive brain infarctions and subsequent encephalomalacia as well as brain atrophy. Skin biopsy found it was consistent with the vesicular stage of IP. Genetic analysis revealed a deletion exon 4-10 in NEMO gene associated with IP. We hereby report a Korean female baby with IP confirmed by mutation analysis of NEMO gene.

Incontinentia pigmenti: presentación neonatal: a propósito de un caso clínico / Incontinentia pigmenti: neonatal presentation: a purpose of clinical case

La incontinentia pigmenti (IP) también conocida como síndrome de Bloch-Sulzberger, es una genodermatosis infrecuente ligada al cromosoma X que afecta tejidos derivados del neuroectodermo: piel, faneras, ojos, sistema nervioso central y dientes. En la etapa neonatal se plantean diagnósticos diferenciales como el impétigo ampollar, herpes neonatal, citomegalovirus, mastocitosis, epidermólisis ampollar hereditaria. El diagnóstico temprano permite detectar las posibles patologías asociadas, que son determinantes para el pronóstico del paciente.

Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is a rare congenital X-linked genodermatosis with variable involvement of tissues derived from neuroectoderm and mesoderm skin, hair, nails, eyes and central nervous system. Differential diagnoses are manifested in the neonatal period, such as bullous impetigo, neonatal herpes, cytomegalovirus, mastocytosis and hereditary epidermolysis bullosa. Early diagnosis allows detection of associated diseases which determine the patients prognosis.

Hidrops fetal como manifestación ecográfica de una enfermedad familiar: incontinentia pigmenti (síndrome de bloch-sulzberger) / Hydrops fetalis as a echographic manifestations of a familial disease: incontinentia pigmenti (bloch-sulzberger syndrome)

Diagnóstico de un caso de enfermedad familiar a partir de un hidrops fetal. Gestante con 2 abortos previos ocurridos al inicio del segundo trimestre, ambos fetos masculinos. Se detecta en la semana 12 un higroma quístico en el contexto de un hidrops fetal. Estudio serológico (TORCH y parvovirus B12), con resultado negativo y biopsia corial con cariotipo 46 XY. La anamnesis y exploración detallada hacen sospechar una enfermedad ligada al cromosoma X, dado que la paciente y una hermana están afectas de una genodermatosis desde la infancia: Incontinentia Pigmenti.

We revealed a family disease by a fetal anomaly. The patient had a history of two early miscarriages of male fetuses. In the present pregnancy hydrops fetalis was demonstrated by routine ultrasound sean at 12 weeks. Serological tests were negative and chorionic villous sampling revealed normal karyotype, 46XY. We suspected a X-linked disease. Detailed family history leaded to the demonstration that the patient and a sister were affected of a rare genodermatosis: Incontinentia Pigmenti.

case report of incontinentia pigmenti

Incontinentia Pigmenti [IP] [Bloch_Sulzberg syndrome] is a rare neurocutaneous syndrome characterized by multisystemic involvement that is prenatally lethal in the majority of affected males and shows great clinical variability when expressed in women. The diagnosis of IP is performed based on clinical features and the family history with the support of histological findings. We report a 10-day-old female neonate with typical skin lesions and frequent seizure. Skin biopsy showed second stage IP

The Common NF-kappaB Essential Modulator (NEMO) Gene Rearrangement in Korean Patients with Incontinentia Pigmenti

Incontinentia pigmenti (IP) is a rare X-linked dominant disorder characterized by highly variable abnormalities of the skin, eyes and central nervous system. A mutation of the nuclear factor-kappa B essential modulator (NEMO) located at Xq28 is believed to play a role in pathogenesis and the mutation occurs mostly in female patients due to fatal consequence of the mutation in males in utero. This study was designed to identify the common NEMO rearrangement in four Korean patients with IP. Deletion of exons 4 to 10 in the NEMO, the most common mutation in IP patients, was detected in all of the patients by the use of long-range PCR analysis. This method enabled us to discriminate between NEMO and pseudogene rearrangements. Furthermore, all of the patients showed skewed XCI patterns, indicating pathogenicity of IP was due to cells carrying the mutant X chromosome. This is the first report of genetically confirmed cases of IP in Korea.

Incontinentia pigmenti - síndrome de Bloch-Sulzberger: relato de caso / Incontinentia pigmenti - Bloch-Sulzberger's syndrome: case report

Relato de um caso de Incontinentia Pigmenti (IP), genodermatose rara ligada ao cromossoma X, caracterizada por erupçäo cutânea e alteraçöes multissistêmicas. As lesöes cutâneas apresentam-se em três estágios sucessivos: lesöes vesiculares, verrucosas e com hiperpigmentaçäo, mas, raramente, surgem ao mesmo tempo. Descreve-se um caso no qual as lesöes cutâneas surgiram simultaneamente

Incontinencia de pigmento: informe de cinco casos en una familia en tres generaciones / incontinentia pigmenti: report of five cases in family in three generations

Se reportan cinco pacientes con incontinencia de pigmento pertenecientes a una familia, quienes han padecido la misma enfermedad desde el nacimiento. Todas del sexo femenino, dos de ellas con complicaciones oculares severas. Se hace una descripción de la enfermedad, sus complicaciones y formas de establecer el diagnóstico; se señala la importancia del consejo genético

Epilepsia e incontinência pigmentar: relato de caso e revisäo de literatura / Epilepsy and incontinentia pigmenti: case report and review of literature

Os autores fazem breve revisäo da literatura sobre Incontinência Pigmentar. Um caso da forma esporádica da síndrome, ocorrido no ambulatório de epilepsia do HU da UFJF, é relatado.

Incintinentia pigmenti: seguimento de uma familia durante 30 años / Incontinention pigment: followring of a family during 30 years

Se comunica el caso de una familia en la cual tres miembros están afectados de Incocntinentia Pigmenti. El Prospositus - cuya enfermedad se debe aparentemente a una mutación - fue seguindo por uno de los autores durante 30 años, de manera que el estudio abarca en realidad tres generaciones

Incontinentia pigmenti, asociaciones oculares, neurológicas y forma unimetamérica / Incontinentia pigmenti, ocular and neurologic association and unilateral metameric distribution

Se presentan tres pacientes con Incontinentia Pigmenti (Síndrome de Bloch-Sulzberger), todos ellos del sexo femenino, siendo dos hermanas con anomalías oculares y neurológicas concomitantes y un tercer caso, linear localizado. Se pasa revista a las principales características de esta entidad