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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
De novo somatic mutations are well documented in diseases such as neoplasia but are rarely reported in rare diseases. Hovewer, severe genetic diseases that are not compatible with embryonic ...development are caused exclusively by deleterious mutations that could only be found as mosaic and not as inherited mutations. We will review here the paradigmatic case of Incontinentia Pigmenti, a rare X-linked dominant disease caused by deficiency of the NEMO (also called IKKgamma) protein, which plays a pivotal role in tissue homeostasis. The loss-of-function mutations of
are embryonically lethal in males while females survive because of unbalanced X-inactivation due to NEMO wild type (WT) expressing cells survival despite of NEMO mutant expressing cells. The few surviving IP males are obligatory mosaic mutants with the typical clinical presentation of IP in female. Indeed, the IP pathogenesis in the female and most likely also in the male somatic mosaics is based on the cellular effects of an impaired NEMO activity, but in the context of the interaction of genetically different cells in the affected tissue, which might underline the inflammatory status.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The objective of this study was to present a systematic review of the central nervous system (CNS) types of anomalies and to consider the possibility to include CNS anomalies in Incontinentia ...pigmenti (IP) criteria. The analyzed literature data from 1,393 IP cases were from the period 1993-2012. CNS anomalies were diagnosed for 30.44% of the investigated IP patients. The total number of CNS types of anomalies per patient was 1.62. In the present study there was no significantly higher number of anomalies per patient in females than males. The most frequent CNS types of anomalies were seizures, motor impairment, mental retardation, and microcephaly. The most frequently registered CNS lesions found using brain imaging methods were brain infarcts or necrosis, brain atrophies, and corpus callosum lesions. IKBKG exon 4-10 deletion was present in 86.00% of genetically confirmed IP patients. The frequency of CNS anomalies, similar to the frequency of retinal anomalies in IP patients, concurrent with their severity, supports their recognition in the list of IP minor criteria.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
La incontinencia pigmenti (síndrome de Bloch-Sulzberger) es una displasia neuroectodérmica infrecuente, con patrón de herencia ligado al X dominante, causada por mutaciones en el gen IKBKG/NEMO y se encuentra localizado en Xq28. La deleción del exón 4 al 10 corresponde con la principal causa en aproximadamente el 80% de los casos. La incidencia estimada es de 0,7 en 100.000 nacimientos, usualmente letal en hombres hemicigotos y en el sexo femenino puede exhibir hallazgos clínicos variables. Es una entidad multisistémica, que incluye defectos en la piel, siempre presente y principal criterio diagnóstico, la cual evoluciona en cuatro etapas, asociada a alteraciones en el sistema nervioso central, globo ocular, dientes, glándula mamaria, pelo, uñas, entre otros. El objeto de esta breve revisión es resaltar los hallazgos clínicos de esta genodermatosis, con la finalidad de brindar el seguimiento médico individualizado e interdisciplinario que incluya un adecuado asesoramiento genético familiar.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Incontinentia pigmenti is a rare genodermatosis of inheritance linked to the X chromosome that affects tissues derived from ectoderm. The aim of the study is to review, as completely as possible, the ...cases diagnosed in paediatric patients in two hospitals.
A retrospective cross-sectional study was carried out, using the clinical, analytical, radiological, and genetic data of paediatric patients diagnosed with incontinentia pigmenti from 2004 to 2018. The data collected were analysed and evaluated at a multidisciplinary level.
A total of thirteen patients diagnosed with incontinentia pigmenti were included in the study. All of them were female. A genetic study was performed on 11 patients, which confirmed findings compatible with incontinentia pigmenti in 10 of them. Extracutaneous involvement associated with the disease was observed at neurological level (radiological findings in 6 cases, and clinical expression in 3 of them), ophthalmological level (4 cases), dental level (7 cases), and haematological level (4 cases).
A presentation is given of the most complete study published so far of incontinentia pigmenti in Spain. In this study, the results of the disease manifestations were similar to the largest case series published internationally, which reinforces the importance of a multidisciplinary study and follow-up.
La incontinencia pigmenti es una genodermatosis poco frecuente, de herencia ligada al cromosoma X, que afecta a tejidos derivados del ectodermo. Nuestro objetivo es revisar de la forma más completa posible los casos diagnosticados en edad pediátrica en dos hospitales.
Se ha realizado un estudio transversal retrospectivo, recogiéndose datos clínicos, analíticos, radiológicos y genéticos valorados a nivel multidisciplinar de pacientes diagnosticados en la edad pediátrica de incontinencia pigmenti desde el año 2004 al 2018.
Se incluyeron 13 pacientes diagnosticados de incontinencia pigmenti, todas de sexo femenino. Se realizó estudio genético en 11 de las 13, confirmándose alteraciones compatibles en 10 de ellas. Se observó afectación extracutánea relacionada con la enfermedad a nivel neurológico (con alteraciones radiológicas en 6 casos y expresión clínica en 3 de ellas), oftalmológico (4 casos), odontológico (7 casos) y hematológico (4 casos).
Presentamos el estudio más completo publicado hasta ahora de incontinencia pigmenti en España. Los resultados del estudio de las manifestaciones de la enfermedad fueron similares a las series de casos más amplias publicadas a nivel internacional y refuerzan la importancia de un estudio y seguimiento multidisciplinar.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Incontinentia pigmenti (IP) is a rare X-linked neuroectodermal dysplasia affecting the skin, hair, teeth, nails, microvasculature, and central nervous system. Mutations in the
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 (IP) is a skin disorder with neurological impairment in 30% of cases. The most common disease causing mutation is a deletion of exons 4-10 of the IKBKG gene, located on ...chromosome Xq28, with skewed X-chromosome inactivation in females, but few cases of random X-inactivation have been reported. We have correlated brain anomalies with X-chromosome inactivation status determined on leucocytes circulating DNA. We reviewed MRI of 18 girls with genetically proven IP. We found three patterns of MRI, normal MRI (n=5), mild white matter abnormalities with cortical and corpus callosum atrophy (n=6), and severe cortical abnormalities suggesting a vascular disease (n=7). Most patients with severe abnormalities had random X-inactivation (6/7,86%), while 80% (4/5) of patients with normal MRI and 100% (6/6) of patients with mild white matter abnormalities had skewed inactivation. These results suggest that skewed chromosome X-inactivation may protect brain from damage, while in case of random inactivation, expression of the mutated IKBKG gene may lead to severe brain lesions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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