Aggressive desmoid fibromatosis in Kabuki syndrome: Expanding the tumor spectrum

Scala, Marcello; Morana, Giovanni; Sementa, Angela Rita; Merla, Giuseppe; Piatelli, Gianluca; Capra, Valeria; Pavanello, Marco

doi:10.1002/pbc.27831

Cited by 7 publications

(9 citation statements)

References 15 publications

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“…This patient's prognosis was assessed to not be different from sporadic cases, but constitutional molecular defects associated with KS may play a role in oncogenesis [155,156]. The tumor spectrum was expanded to include: a low-grade fibromyxoid sarcoma in a clinically diagnosed KS patient-the mass was successfully resected [157]; and a case of aggressive desmoid fibromatosis, successfully treated surgically [158].…”

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

Kabuki Syndrome—Clinical Review with Molecular Aspects

Boniel

Sztefko

Śmigiel

et al. 2021

Genes

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Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most common cause of KS and account for up to 75% of patients. Variants in KDM6A cause up to 5% of cases (X-linked dominant inheritance), while the etiology of about 20% of cases remains unknown. Current KS diagnostic criteria include hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphism and confirmed pathogenic/likely pathogenic variant in KMT2D or KDM6A. Care for KS patients includes the control of physical and psychomotor development during childhood, rehabilitation and multi-specialist care. This paper reviews the current clinical knowledge, provides molecular and scientific links and sheds light on the treatment of Kabuki syndrome individuals.

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Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

Kabuki Syndrome—Clinical Review with Molecular Aspects

Boniel

Sztefko

Śmigiel

et al. 2021

Genes

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“…(OMIM 243800) UBR1 (AR) [7,40] Kabuki sy. (OMIM PS147920) KDM6A (XLD); KMT2D (AD) [7,41] Klippel-Trenaunay-Weber sy. (OMIM 149000) PIK3CA (unkown); but mostly unkown [15,42] Lipomatoses /heterogenous group of multiple lipomas, they are nearly always benign/ unkown (possibly heterogenous, poligenic & multifactorial) [15] Marfan sy.…”

Section: Genetic Background (Inheritance) Referencesmentioning

confidence: 99%

Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

et al. 2021

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Background Neurofibromatosis type 1 (NF1), which is caused by heterozygous inactivating pathogenic variants in the NF1, has poor phenotypic expressivity in the early years of life and there are numerous conditions, including many other tumor predisposition syndromes, that can mimic its appearance. These are collectively termed NF1-like syndromes and are also connected by their genetic background. Therefore, the NF1’s clinical diagnostic efficiency in childhood could be difficult and commonly should be completed with genetic testing. Methods To estimate the number of syndromes/conditions that could mimic NF1, we compiled them through an extensive search of the scientific literature. To test the utility of NF1’s National Institutes of Health (NIH) clinical diagnostic criteria, which have been in use for a long time, we analyzed the data of a 40-member pediatric cohort with symptoms of the NF1-like syndromes’ overlapping phenotype and performed NF1 genetic test, and established the average age when diagnostic suspicion arises. To facilitate timely identification, we compiled strongly suggestive phenotypic features and anamnestic data. Results In our cohort the utility of NF1’s clinical diagnostic criteria were very limited (sensitivity: 80%, specificity: 30%). Only 53% of children with clinically diagnosed NF1 had a detectable NF1 pathogenic variation, whereas 40% of patients without fulfilled clinical criteria tested positive. The average age at first genetic counseling was 9 years, and 40% of children were referred after at least one tumor had already been diagnosed. These results highlight the need to improve NF1-like syndromes’ diagnostic efficiency in childhood. We collected the most extensive spectrum of NF1-like syndromes to help the physicians in differential diagnosis. We recommend the detailed, non-invasive clinical evaluation of patients before referring them to a clinical geneticist. Conclusions Early diagnosis of NF1-like syndromes can help to prevent severe complications by appropriate monitoring and management. We propose a potential screening, diagnostic and management strategy based on our findings and recent scientific knowledge.

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“… 94 Moreover, KMT2D alterations are involved in intraocular medulloepithelioma, 95 small cell lung cancer, 96 bladder cancer, 97 98 and non-small-cell lung cancer. 99 Of not less importance, alterations of KMT2D have a causal role in Kabuki syndrome 100 that is characterized by skeletal and visceral abnormalities and cardiac anomalies, 101 hyperinsulinism, 102 epilepsy, 103 desmoid fibromatosis, 104 immunopathological manifestations, 105 lupus, 106 and oriental alterations, 107 among others.…”

Section: Resultsmentioning

confidence: 99%

From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

Kanduc

Shoenfeld

2020

Global Medical Genetics

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Sequence analyses highlight a massive peptide sharing between immunoreactive Epstein-Barr virus (EBV) epitopes and human proteins that—when mutated, deficient or improperly functioning—associate with tumorigenesis, diabetes, lupus, multiple sclerosis, rheumatoid arthritis, and immunodeficiencies, among others. Peptide commonality appears to be the molecular platform capable of linking EBV infection to the vast EBV-associated diseasome via cross-reactivity and questions the hypothesis of the “negative selection” of self-reactive lymphocytes. Of utmost importance, this study warns that using entire antigens in anti-EBV immunotherapies can associate with autoimmune manifestations and further supports the concept of peptide uniqueness for designing safe and effective anti-EBV immunotherapies.

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Aggressive desmoid fibromatosis in Kabuki syndrome: Expanding the tumor spectrum

Cited by 7 publications

References 15 publications

Kabuki Syndrome—Clinical Review with Molecular Aspects

Kabuki Syndrome—Clinical Review with Molecular Aspects

Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

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