Diffuse cutaneous mastocytosis with novel somatic <scp>KIT</scp> mutation K509I and association with tuberous sclerosis

Otani, Iris M.; Carroll, Ryan W.; Yager, Phoebe; Kroshinsky, Daniela; Murphy, Sarah; Hornick, Jason L.; Akin, Cem; Castells, Mariana; Walter, Jolán E.

doi:10.1002/ccr3.1607

Cited by 11 publications

(11 citation statements)

References 32 publications

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“…Heritability associated with germline mutations of KIT is extremely rare in mastocytosis, and these germline KIT mutations occur in different gene regions such as N822I, F522C, K509I, S451C, R634W, Del 419, A533D, S476I, among others [ 17 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Of note, rare cases of mastocytosis with germline KIT mutations associated with tuberous sclerosis and gastrointestinal stromal tumors were reported [ 35 , 36 , 39 ]. In families in which mastocytosis is inherited in an autosomal dominant pattern, patients usually have increased tryptase levels, extracutaneous involvement and a chronic course of the disease [ 31 , 36 , 37 , 39 ].…”

Section: Pathogenesismentioning

confidence: 99%

Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021

Lange

Hartmann

Carter

et al. 2021

IJMS

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Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the KIT proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self-limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small-sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator-related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto-injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow-up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood.

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Section: Pathogenesismentioning

confidence: 99%

Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021

Lange

Hartmann

Carter

et al. 2021

IJMS

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“…Allergic symptoms, due to mediators secreted from mast cells, have been significantly correlated with ASD severity [183,188]. A recent paper reported that diffuse cutaneous mastocytosis with the novel somatic KIT mutation K509I was associated with tuberous sclerosis, most of the may affected patient of which have ASD [189]. Large epidemiological studies have reported that allergies and asthma in preschoolers are significantly associated with ASD [190][191][192][193].…”

Section: Comorbiditiesmentioning

confidence: 99%

Recent advances in our understanding of mast cell activation – or should it be mast cell mediator disorders?

Theoharides

Tsilioni

Ren

2019

Expert Review of Clinical Immunology

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Introduction: An increasing number of patients present with multiple symptoms affecting many organs including the brain due to multiple mediators released by mast cells. These unique tissue immune cells are critical for allergic reactions triggered by immunoglobulin E (IgE), but are also stimulated (not activated) by immune, drug, environmental, food, infectious, and stress triggers, leading to secretion of multiple mediators often without histamine and tryptase. The presentation, diagnosis, and management of the spectrum of mast cell disorders are very confusing. As a result, specialists have recently excluded neuropsychiatric symptoms, and made the diagnostic criteria stricter, at the expense of excluding most patients.

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“…According to current knowledge, genetic drivers, epigenetics, and both hormonal and metabolic factors involved in the pathogenesis of pediatric mastocytosis are poorly understood [ 1 , 3 , 8 ]. However, numerous studies show that children with DCM can carry different somatic mutations in exon 17 of KIT (D816V, D816Y, or D816I), as well as mutations in other exons (Del419, K509I, or internal tandem duplication A502_Y503dup) [ 18 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Familial mastocytosis is a specific form of the disease in which mostly germline KIT mutations are detected in affected family members [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ].…”

Section: Genetic Background Of Diffuse Cutaneous Mastocytosismentioning

confidence: 99%

Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease

Rydz,

Lange,

Ługowska-Umer

et al. 2024

IJMS

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Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier’s sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

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Diffuse cutaneous mastocytosis with novel somatic KIT mutation K509I and association with tuberous sclerosis

Cited by 11 publications

References 32 publications

Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021

Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021

Recent advances in our understanding of mast cell activation – or should it be mast cell mediator disorders?

Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease

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