Skin and Mucosal Manifestations in NEMO Syndrome: A Case Series and Literature Review

Kohn, Lucinda L.; Braun, Mitchell; Cordoro, Kelly M.; McCalmont, Timothy H.; Shah, Sonal D.; Frieden, Ilona J.; Mathur, Anubhav N.

doi:10.1111/pde.14905

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…Xerotic skin may take the form of severe ichthyotic like lesions. Various other cutaneous manifestations occur, including oral and perineal ulcers, palmoplantar keratoderma, hypopigmented papules seborrheic dermatitis, prurigo, and erythroderma, which may be severe ( 69 ).…”

Section: Inborn Errors Of Nf-κb and Skin Pathologymentioning

confidence: 99%

“…Extracutaneous manifestations can include hypodontia, delayed tooth eruption and abnormal tooth shape (conical, accessory cusps, tulip-shaped teeth, and microdontia), low nasal bridge, frontal bossing and hypoplastic nasal alae ( 49 , 69 , 70 ). Severely affected individuals may show osteopetrosis and lymphedema ( 71 ).…”

Section: Inborn Errors Of Nf-κb and Skin Pathologymentioning

confidence: 99%

“…Isolated phenotypic features can phenotypes arise from defects in receptors responding to cues in cells that also signal though IKK ( 72 , 73 ). At the other end of the spectrum, IKBKG mutations can present with mucocutaneous phenotypes of ichthyosis, eczematous dermatitis, palmoplantar keratoderma and recurrent mucocutaneous ulcers ( 69 ).…”

Section: Inborn Errors Of Nf-κb and Skin Pathologymentioning

confidence: 99%

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Skin manifestations of inborn errors of NF-κB

et al. 2023

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More than 400 single gene defects have been identified as inborn errors of immunity, including many arising from genes encoding proteins that affect NF-κB activity. We summarise the skin phenotypes in this subset of disorders and provide an overview of pathogenic mechanisms. NF-κB acts cell-intrinsically in basal epithelial cells during differentiation of skin appendages, influences keratinocyte proliferation and survival, and both responses to and amplification of inflammation, particularly TNF. Skin phenotypes include ectodermal dysplasia, reduction and hyperproliferation of keratinocytes, and aberrant recruitment of inflammatory cells, which often occur in combination. Phenotypes conferred by these rare monogenic syndromes often resemble those observed with more common defects. This includes oral and perineal ulceration and pustular skin disease as occurs with Behcet's disease, hyperkeratosis with microabscess formation similar to psoriasis, and atopic dermatitis. Thus, these genotype-phenotype relations provide diagnostic clues for this subset of IEIs, and also provide insights into mechanisms of more common forms of skin disease.

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Section: Inborn Errors Of Nf-κb and Skin Pathologymentioning

confidence: 99%

Section: Inborn Errors Of Nf-κb and Skin Pathologymentioning

confidence: 99%

Section: Inborn Errors Of Nf-κb and Skin Pathologymentioning

confidence: 99%

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Skin manifestations of inborn errors of NF-κB

et al. 2023

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“…These authors suggested a therapeutic potential for receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibition in IBD patients, after demonstrating that RIPK1 prevented epithelial cell death and colitis development in NEMO IEC−KO mice [ 99 ]. Although this pre-clinical model is of use to study the interactions between the intestinal microbiome and spontaneous colitis, NEMO-deficient patients exhibit a variety of mucocutaneous diseases, and it is feasible that they may also carry concomitant mutations in IBD-associated genes [ 100 ].…”

Section: Spontaneous Colitismentioning

confidence: 99%

Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease

Katsandegwaza

Horsnell

Smith

2022

IJMS

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Crohn’s disease (CD) and ulcerative colitis (UC) are both highly inflammatory diseases of the gastrointestinal tract, collectively known as inflammatory bowel disease (IBD). Although the cause of IBD is still unclear, several experimental IBD murine models have enabled researchers to make great inroads into understanding human IBD pathology. Here, we discuss the current pre-clinical experimental murine models for human IBD, including the chemical-induced trinitrobenzene sulfonic acid (TNBS) model, oxazolone and dextran sulphate sodium (DSS) models, the gene-deficient I-kappa-B kinase gamma (Iκκ-γ) and interleukin(IL)-10 models, and the CD4+ T-cell transfer model. We offer a comprehensive review of how these models have been used to dissect the etiopathogenesis of disease, alongside their limitations. Furthermore, the way in which this knowledge has led to the translation of experimental findings into novel clinical therapeutics is also discussed.

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“…The phenotype may be very similar to that of XLHED due to the common molecular signaling pathway [ 6 , 7 , 8 ]. Patients with Incontinentia pigmenti (IP; MIM #308300), a rare X-linked disorder caused by pathogenic variants of the gene IKBKG (MIM *300248) display a characteristic skin blistering during early infancy followed by hyperpigmentation, tooth anomalies, sparse hair, and sometimes severe involvement of the eyes and the central nervous system [ 9 ]. In hemizygous males, IP is associated with severe immunodeficiency which is usually lethal.…”

Section: Introductionmentioning

confidence: 99%

Congenital Nail Disorders among Children with Suspected Ectodermal Dysplasias

Maier-Wohlfart

Aicher

Willershausen

et al. 2022

Genes

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We report on a cohort of 204 children referred between January 2017 and January 2022 to the German Center for Ectodermal Dysplasias, Erlangen. The most frequent reasons for referral were tooth malformations and lack of multiple teeth leading to the suspicion of an ectodermal dysplasia. Many patients also suffered from being unable to perspire. Nail abnormalities, in contrast, represented a much rarer finding, albeit the impact on some individuals was large. As ectodermal dysplasias are congenital genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands, we analyzed congenital nail disorders detected in these patients. Dystrophic or otherwise abnormal nails were evident in 17 of 18 subjects with pathogenic WNT10A or GJB6 variants but in none of 161 children with EDA variants underlying X-linked hypohidrotic ectodermal dysplasia. However, 2 of 17 children who carry mutations in EDAR or EDARADD, two other genes involved in the ectodysplasin A signaling pathway, showed nail abnormalities, such as brittle or hypoplastic nails. TP63 variants were regularly associated with nail disorders. In one girl, anonychia congenita caused by a compound heterozygous variant of the R-spondin-4 gene (RSPO4) was diagnosed. Thus, nail dysplasia is rarer among patients with ectodermal dysplasia than commonly thought.

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Skin and Mucosal Manifestations in NEMO Syndrome: A Case Series and Literature Review

Cited by 7 publications

References 26 publications

Skin manifestations of inborn errors of NF-κB

Skin manifestations of inborn errors of NF-κB

Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease

Congenital Nail Disorders among Children with Suspected Ectodermal Dysplasias

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