Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal disorder characterized by ocular, dermatologic, and neurological abnormalities. It is caused by heterozygous mutations in IKBKG ...(NEMO), which encodes a regulatory factor involved in NF-kB activation. Random and skewed X-inactivation allows for female survival and determines extent of disease. Although immune function is typically normal in IP patients, hypomorphic IKBKG mutations are known to cause immunodeficiency, as occurs in X-linked NEMO deficiency. A female newborn presented with bullous vesicles, peeling skin, alopecia, hearing loss, and tonic-clonic seizures with MRI demonstrating evidence of in utero stroke. She developed intermittent fevers and cellulitis and was diagnosed with IP based on clinical findings. Following discharge, she was readmitted at 1 month of age due to bronchiolitis complicated by pulmonary abscess. Labs demonstrated hyperleukocytosis with hypereosinophilia, normal T, B, and NK lymphocyte enumeration, abnormal lymphocyte proliferation to phytohemagglutinin (PHA) and anti-CD3, and abnormal toll-like receptor (TLR) function. Genetic analysis revealed a heterozygous deletion of exons 4–10 in IKBKG. Labs at 1 year follow up showed normal lymphocyte (T, B, and NK) enumeration and mitogen responses, normal immunoglobulin levels, and normal responses to pneumococcal and tetanus vaccines. While about 70% of IP patients harbor a deletion of exons 4–10 in IKBKG. unlike other hypomorphic NEMO mutations, this mutation is not typically associated with altered immune function. This case highlights that immunodeficiency may be an early clinical manifestation in female patients with IP.
In 1993 diagnostic criteria for incontinentia pigmenti (IP), a genodermatosis in which skin changes are usually combined with anomalies of other organs, were established. Approximately a decade ago, ...IKBKG gene mutation was discovered as a cause for IP. This finding has not been included in IP diagnosis so far. In addition, literature data pointed out a few other clinical findings as possible IP diagnostic criteria. Literature facts concerning IP diagnosis were analyzed. Different organ anomalies, their frequency and severity, were analyzed in the context of applicability as IP diagnostic criteria. Taking into account analyzed data from the literature, the proposal of updated IP diagnostic criteria was presented. We propose as major criteria one of the stages of IP skin lesions. As updated IP minor criteria in our proposal we included: dental, ocular; central nervous system (CNS), hair, nail, palate, breast and nipple anomalies; multiple male miscarriages, and IP pathohistological findings. In the diagnosis of IP, the presence of IKBKG mutation typical for IP, and existence of family relatives with diagnosed IP are taken into account.
Ein ungewöhnlicher Verlauf von Incontinentia pigmenti Sigl, Jannina; Vodopiutz, Julia; Tanew, Adrian ...
Journal der Deutschen Dermatologischen Gesellschaft,
February 2020, 2020-02-00, 20200201, Letnik:
18, Številka:
2
Journal Article
X-linked dominant incontinentia pigmenti (IP) and X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) are caused by loss-of-function and hypomorphic IKBKG (also known as ...NEMO) mutations, respectively. We describe a European mother with mild IP and a Japanese mother without IP, whose 3 boys with EDA-ID died from ID. We identify the same private variant in an intron of IKBKG, IVS4+866 C>T, which was inherited from and occurred de novo in the European mother and Japanese mother, respectively. This mutation creates a new splicing donor site, giving rise to a 44-nucleotide pseudoexon (PE) generating a frameshift. Its leakiness accounts for NF-κB activation being impaired but not abolished in the boys' cells. However, aberrant splicing rates differ between cell types, with WT NEMO mRNA and protein levels ranging from barely detectable in leukocytes to residual amounts in induced pluripotent stem cell-derived (iPSC-derived) macrophages, and higher levels in fibroblasts and iPSC-derived neuronal precursor cells. Finally, SRSF6 binds to the PE, facilitating its inclusion. Moreover, SRSF6 knockdown or CLK inhibition restores WT NEMO expression and function in mutant cells. A recurrent deep intronic splicing mutation in IKBKG underlies a purely quantitative NEMO defect in males that is most severe in leukocytes and can be rescued by the inhibition of SRSF6 or CLK.
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.
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).
Introduction
Incontinentia pigmenti (IP) is a rare X‐linked dominant genetic disease affecting ectodermal tissue and often misdiagnosed in the neonatal period. The aim of this study was to highlight ...sequential clinical features and evaluate prognosis of the 32 neonatal IP patients.
Material and methods
A retrospective descriptive analysis was performed, using the clinical, blood analytical, pathological, radiological, genetic, and followed‐up data of neonatal patients diagnosed with IP from 2010 to 2021, in Xi'an, China.
Results
Of the 32 patients, two (6.25%) were male. Thirty babies (93.75%) had eosinophilia (eosinophilic granulocyte count: 0.31–19.9 × 109, mean proportion of white blood cells: 20.98 ± 15.21%). Twenty babies (62.5%) had thrombocytosis (thrombocyte count: 139–975 × 109, mean count: 416.76 ± 176.82). Thirty‐one babies (96.88%) exhibited the first three cutaneous lesion stages characterized by erythema and superficial vesicles on inflammatory bases in a linear distribution in the first week of age. Thirteen babies (40%) combined nervous system abnormalities, and nine babies (28.13%) had retinopathy. Two types of genetic mutations were detected in the NEMO gene. Nineteen babies were followed up. According to the follow‐up, four babies displayed psychomotor retardation, and five babies developed a decrease in vision with astigmatism and amblyopia.
Conclusion
It is important that 30 babies (93.75%) had eosinophilia and 20 babies (62.5%) had thrombocytosis. Therefore, we speculate that the mechanism of the injury may be related to the platelet aggregation on the basis of the increase in eosinophil cells and the release of inflammatory factors.
Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that affects skin, hair, teeth, eyes and central nervous system. We present the case of a female patient with mild IP caused by ...a hypomorphic pathogenic variant of the inhibitor of the kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG) gene. This is the first report of a female IP patient with the hypomorphic variant, NM_001099856.6: c.1423dup, which is causative of anhidrotic ectodermal dysplasia with immune deficiency in males.
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